Sickle Cell News for 2013
Anti-sickling therapies should be focus for sickle cell science http://www.eurekalert.org/pub_releases/2013-04/mcog-ats041713.php
Pain is an undeniable focal point for patients with sickle cell disease but it's not the best focus for drug development, says one of the dying breed of physicians specializing in the condition.
Rather scientists need to get back to the crux of the disease affecting 1 in 500 black Americans and find better ways to prevent the hallmark sickling that impedes red blood cells' oxygen delivery, damaging blood vessel walls and organs along the way, said Dr. Abdullah Kutlar, Director of the Sickle Cell Center at the Medical College of Georgia at Georgia Regents University.
"We have one drug that reduces sickling and we need more," said Kutlar, the 2013 Roland B. Scott, M.D., Lecturer for the 7th Annual Sickle Cell Disease Research and Educational Symposium and National Sickle Cell Disease Scientific Meeting April 14-17 in Miami.
"Pain is very important to someone who is suffering, but by using pain as an end point, we are missing opportunities and wasting drugs that could be very helpful," he said. "Moving forward, I suggest we develop new combination therapies that have anti-sickling capabilities at their center," said Kutlar, noting such cocktail approaches have worked well for cancer and HIV.
Kutlar completed an extensive historical review of patient and study outcomes in preparation for the lecture honoring the late Howard University physician who made it his mission to improve the lives of children with sickle cell disease. Scott's contributions include prompting the National Sickle Cell Control Act of 1972, which established the first federally-funded comprehensive sickle cell centers, including the one at MCG led by Dr. Titus H.J. Huisman.
No doubt Scott, Huisman and others have made a tremendous difference to patients, whose average life expectancy has gone from the teens to the 50s in the past 30 years, Kutlar said. Much of that progress grew out of focusing on the basics, including developing hydroxyurea, still the only Food and Drug Administration-approved drug that targets sickling.
Approved 15 years ago, hydroxyurea works by increasing expression of fetal hemoglobin, which can't sickle. However, it's still not widely used – about 35 percent of Kutlar's adult patients take it, for example – probably for a combination of reasons that include a side effect of weight gain and unsubstantiated concerns that it increases cancer risk. He and his colleagues need to do a better job communicating the benefits of this drug in addition to finding new ones, Kutlar said. Reduced sickling means less damage to blood vessels and organs, he said, noting that the major cause of death in adults and children is acute chest syndrome, a severe pneumonia resulting from cumulative lung damage. A handful of new anti-sickling drugs are in various stages of development, including a thalidomide- derivative pioneered by MCG researchers that also enhances fetal hemoglobin expression.
Other good endpoints for drug development include downstream effects of sickling, such as the unnatural adhesion of red blood cells to blood vessel walls, Kutlar said. Unfortunately work was recently halted on a drug that reduced adhesion but not pain, Kutlar said.
Pain needs to be the primary endpoint only for pain medications, he noted. The good news is that many new pain medications are available for these patients, whose pain crises can be severe enough to require hospitalization and whose chronic pain can impair daily living. However, that circles back to the complex causes of pain. The pain initially likely results from tissues crying out for more oxygen and later from nerve and organ damage resulting from ongoing impaired oxygen supplies. Pain control can get even more complex and difficult because regular use of opiates, a common analgesic for sickle cell patients, actually increases pain sensitivity, Kutlar said.
In addition to finding better therapies, physicians who treat sickle cell patients need to help cultivate the next generation of caregivers, Kutlar said. He's in the minority in that he opted to take care of patients with sickle cell disease rather than pursue the more common – and generally more professionally lucrative – hematology path: treating cancer. "We don't have enough hematologists, period," said Kutlar. The problem does have a good cause: the reality that more patients are living longer. However, the number of physicians to treat adult patients is dismal. Helping cultivate the next generation is a focus of a study led by Kutlar and Dr. Robert W. Gibson, a GRU occupational therapist and medical anthropologist. They are reaching out to primary care physicians – who also are in short supply in this country – as a permanent medical home for patients as they reach adulthood. Kutlar and Gibson are co-principal investigators on $7 million, five-year grant from the National Center on Minority Health and Health Disparities of the National Institutes of Health supporting this initiative as well as the search for new drugs and more.
MCG physicians follow about 1,500 adults and children with sickle cell disease.
Clinical Research Forum selects sickle cell project among 'Top 10' clinical research achievements of 2012 http://www.news-medical.net/news/20130422/Clinical-Research-Forum-selects-sickle-cell-project-among-Top-10-clinical-research-achievements-of-2012.aspx
Pioneering research led by Johns Hopkins scientists on the use of partially matched bone marrow transplants to wipe out sickle cell disease has been selected as one of the Top 10 Clinical Research Achievements of 2012 by the Clinical Research Forum. The success of a preliminary clinical trial of the so-called haploidentical transplants has the potential to bring curative transplants to a majority of sickle cell patients who need them, eliminating painful and debilitating symptoms and the need for a lifetime of pain medications and blood transfusions.
On behalf of the research team, Robert A. Brodsky, M.D., the Johns Hopkins Family Professor of Medicine in Oncology and director of the Division of Hematology at the Johns Hopkins University School of Medicine, will receive the award and an additional honor, the Distinguished Clinical Research Achievement Award, at a ceremony on April 18 during the Clinical Research Forum annual meeting in Washington, D.C.
New Web article Sickle Cell Disease Review
Advances in disease management and new treatment models help patients live longer. 1 contact hour of CEU for nurses:
New Video - Strategies to Improve Implementation of Hydroxyurea
Dr. Courtney Thornburg, Duke Pediatric Sickle Cell Clinic
SAVE THE DATES
Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC
4th Thursday of every month from 2:00PM – 3:00PM EST
5/23: Baby on Board: What You Need to Know about Pregnancy in the Hemoglobinopathies
Dr. Sophie Lanzkron, Sickle Cell Center for Adults at Johns Hopkins Hospital
6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia
Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC
7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations
Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants
8/22: Mental Health and Learning Needs in children with Sickle Cell Disease
Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center
9/26: NHLBI Sickle Cell Disease Guidelines
Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH
10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease
Dr. Winfred Wang, St. Jude Children’s Research Hospital
November/December: --- No Webinars---
If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope firstname.lastname@example.org .
The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.
CDC Web based Sickle Cell Resources
CDC Sickle Cell Disease Webpage: http://www.cdc.gov/NCBDDD/sicklecell/video.html
Articles in the Medical Literature for April
1. J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]
Cytochrome P450 2D6 Polymorphisms and Predicted Opioid Metabolism in African American Children With Sickle Cell Disease.
Yee MM, Josephson C, Hill CE, Harrington R, Castillejo MI, Ramjit R, Osunkwo I.
*Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta Departments of †Pediatrics, Hematology/Oncology ‡Pathology and Laboratory Medicine, Emory University §Emory University School of Medicine, Atlanta, GA.
The opioid medications codeine and hydrocodone, commonly prescribed in sickle cell disease (SCD), require metabolic conversion by cytochrome P450 2D6 (CYP2D6) to morphine and hydromorphone, respectively, to exert their analgesic effects. The CYP2D6 gene is highly polymorphic, with variant alleles that result in decreased, absent, or ultrarapid enzyme activity. Seventy-five children with SCD were tested for CYP2D6 polymorphisms, and metabolic phenotypes were inferred from the genotypes. The most common variant alleles were CYP2D6*2 (normal activity, 28.7%), CYP2D6*17 (reduced activity, 17.3%), CYP2D6*5 (gene deletion, 8.7%), and CYP2D6*4 (absent function, 8.0%). Normal/extensive metabolizer genotypes were found in 28/75 (37.5%), intermediate metabolism in 33/75 (44.0%), poor metabolism in 4/75 (5.3%), ultrarapid metabolism in 3/75 (4.0%), indeterminate in 6/75 (8.0%). Allele frequencies did not vary significantly among different hemoglobin genotypes. Identification of variant CYP2D6 genotypes may identify individuals with altered metabolism and therefore altered analgesic response to codeine and hydrocodone, thus providing a personalized medicine approach to treatment of pain in SCD. Further pharmacokinetic and pharmacodynamic studies are needed to define the relationship of CYP2D6 and other gene polymorphisms to individual opioid effect in SCD.
PMID: 23619115 [PubMed - as supplied by publisher]
2. J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]
Hyperhemolysis in Sickle Cell Disease.
Aragona E, Kelly MJ.
*Division of Hospitalist Medicine, Children's National Medical Center, The George Washington University School of Medicine and Health Sciences, Washington, DC †Division of Pediatric Hematology Oncology, The Floating Hospital for Children at Tufts Medical Center, Tufts University School of Medicine, Boston, MA.
An 18-year-old female with sickle cell disease presented with thigh pain, dark urine, and hematuria within 72 hours of receiving a blood transfusion. Her clinical picture was consistent with hemolysis. Subsequent laboratory workup, however, demonstrated reticulocytopenia without evidence of an antibody-mediated transfusion reaction. As her hemoglobin continued to decrease, she was treated with IVIG and steroids for presumed hyperhemolysis. Clinicians should have a high index of suspicion for hyperhemolysis in sickle cell patients with evidence of hemolysis after a recent transfusion. Differentiating hyperhemolysis from other hemolytic syndromes is critical; transfusions in a hyperhemolytic episode can accelerate hemolysis causing life-threatening anemia.
PMID: 23619113 [PubMed - as supplied by publisher]
3. J Pediatr Hematol Oncol. 2013 May;35(4):289-298.
Barriers to Hematopoietic Cell Transplantation Clinical Trial Participation of African American and Black Youth With Sickle Cell Disease and Their Parents.
Omondi NA, Ferguson SE, Majhail NS, Denzen EM, Buchanan GR, Haight AE, Labotka RJ, Rizzo JD, Murphy EA.
*National Marrow Donor Program †Center for International Blood and Marrow Transplant Research and University of Minnesota, Minneapolis, MN ‡The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, TX §Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA ∥Chicago Sickle Cell Center, University of Illinois, Chicago, IL Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI.
African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.
PMID: 23612380 [PubMed - as supplied by publisher]
4. J Pediatr Hematol Oncol. 2013 May;35(4):329-30. doi: 10.1097/MPH.0b013e318290c5f3.
Sickle Cell-related Bone Marrow Complications: The Utility of Diffusion-weighted Magnetic Resonance Imaging.
Pratesi A, Medici A, Bresci R, Micheli A, Barni S, Pratesi C.
Misericordia e Dolce Hospital, Prato, Tuscany, Italy.
In sickle cell disease diffusion-weighted imaging (DWI) are helpful, cost-effective, and promising techniques for differentiating bone marrow involvements. So we suggest to consider a MR diffusion panoramic study (whole-body diffusion MR) when multiple follow-up imaging is required in young patients who are at high risk for chronic radiation damage, so that alternatives to PET study may be taken into consideration.
PMID: 23612384 [PubMed - in process]
5. Eur Cytokine Netw. 2013 Apr 19. [Epub ahead of print]
Altered levels of pro-inflammatory cytokines in sickle cell disease patients during vaso-occlusive crises and the steady state condition.
Keikhaei B, Mohseni AR, Norouzirad R, Alinejadi M, Ghanbari S, Shiravi F, Solgi G.
Thalassemia & Hemoglobinopathy research center, Ahvaz Joundishapur University of Medical Science, Ahvaz, Iran.
Objective: This study aimed to evaluate serum levels of pro-inflammatory cytokines and TGF-β in sickle cell disease (SCD) patients, and to compare the results during vaso-occlusive crisis (VOC) or steady state (StSt) conditions. Methods: 54 SCD patients (37HbSS and 17Sβ+Thal) were enrolled in the study and evaluated in two groups as follows; group A consisted of 39 VOC patients and group B comprised 15 StSt patients. Nineteen healthy volunteers were included as controls. Circulating levels of IL-1, IL-6, IL-8, IL-17,TNF-α and TGF-β were measured using ELISA. Results: Patients in VOC showed higher mean levels of all cytokines than those found in steady-state patients, but this was only marginally significant for IL-8 levels (P = 0.08). Increased levels of TGF-β and IL-17 were found in StSt patients versus normal controls (P = 0.004 and P<0.0001 respectively). A positive correlation was observed between IL-8 and IL-17 in both groups of patients (P = 0.002 and P = 0.005 respectively). Decreased levels of TNF-α, IL-1β and IL-17 were found in hydroxyurea-treated patients. Additionally, significantly higher levels of IL-6 and IL-8 were observed in hydroxyurea-treated and untreated patients than in controls respectively (P = 0.04 and P = 0.01). Conclusions: Our findings indicate that pro-inflammatory cytokines, especially IL-8 and IL-17, could be used as related markers for assessing disease severity, and consequently therapeutic intervention.
PMID: 23608554 [PubMed - as supplied by publisher]
6. Am J Hematol. 2013 Apr 20. doi: 10.1002/ajh.23457. [Epub ahead of print]
Genetic modifiers of sickle cell anemia in the BABY HUG cohort: Influence on laboratory and clinical phenotypes.
Sheehan VA, Luo Z, Flanagan JM, Howard TA, Thompson BW, Wang WC, Kutlar A, Ware RE; BABY HUG Investigators.
Hematology Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects was analyzed for alpha thalassemia, beta-globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (XmnI, BCL11A, and HBS1L-MYB), UGT1A1 promoter polymorphisms, and the common G6PD A- mutation. At study entry, infants with alpha thalassemia trait had significantly lower MCV, total bilirubin, and absolute reticulocyte count. Beta-globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF. BCL11A and XmnI polymorphisms had significant effects on baseline HbF, while UGT1A1 promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA.
Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.
PMID: 23606168 [PubMed - as supplied by publisher]
7. Hemoglobin. 2013 Apr 19. [Epub ahead of print]
Leg Ulcers in Sickle Cell Disease: Current Patterns and Practices.
Delaney KM, Axelrod KC, Buscetta A, Hassell KL, Adams-Graves PE, Seamon C, Kato GJ, Minniti CP.
National Heart, Lung, and Blood Institute , Bethesda, Maryland , USA.
Leg ulcers are a debilitating complication of patients with sickle cell disease, and their frequency in North America was reported to be 2.5% by the Cooperative Study of Sickle Cell Disease more than 20 years ago. We sought to determine if the frequency of leg ulcers in sickle cell patients in the United States had declined and to assess which treatments providers use most commonly. We sent an e-mail survey to health professionals belonging to the national Sickle Cell Adult Provider Network. Responses were obtained from 31 of them (26.0%). Most of them (96.0%) reported having some patients with leg ulcers. Providers reported a total of 185 patients with active leg ulcers and 224 in the previous 5 years, for a total of 409 patients. Hb SS (homozygous sickle cell anemia) was the most common genotype of affected individuals, followed by Hb SC (double heterozygote for Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T] and Hb C [β6(A3)Glu→Lys, GAG>AAG; HBB: c.19G>A]). Males showed a 2:1 predominance. Two-thirds of patients were treated with either hydroxyurea (HU) or transfusion therapy and most used compression stockings and topical therapies as directed by wound care services. We conclude that leg ulcers continue to be a debilitating complication of young adults with sickle cell disease, despite improved supportive care and the widespread use of disease modifying agents such HU and transfusion. While some providers offer office-based ulcer care, the majority prefer specialty consultation including podiatry, plastic surgery and dermatology. Despite their frequency, there is no clear consensus among providers as to the best treatment.
PMID: 23600469 [PubMed - as supplied by publisher]
8. Br J Haematol. 2013 Apr 18. doi: 10.1111/bjh.12336. [Epub ahead of print]
Interplay between coagulation and vascular inflammation in sickle cell disease.
Sparkenbaugh E, Pawlinski R.
Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sickle cell disease is the most common inherited haematological disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease, the importance of haemolytic anaemia and vasculopathy has been recently recognized. A hypercoagulable state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease.
© 2013 John Wiley & Sons Ltd.
PMID: 23593937 [PubMed - as supplied by publisher]
9. Br J Haematol. 2013 Apr 17. doi: 10.1111/bjh.12323. [Epub ahead of print]
The effect of hydroxcarbamide therapy on survival of children with sickle cell disease.
Lopes de Castro Lobo C, Pinto JF, Nascimento EM, Moura PG, Cardoso GP, Hankins JS.
Instituto de Hematologia Arthur Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ, Brazil.
Although evidence is accumulating that hydroxycarbamide decreases mortality among adults with sickle cell disease (SCD), there are no published data regarding the effect of hydroxycarbamide on mortality among children. The Paediatric Hydroxycarbamide Program was established to treat children with SCD aged 3-18 years if they met disease severity criteria. Mortality data and clinical/laboratorial effects of hydroxycarbamide were retrospectively collected for the first 9 years of the Program. Mortality among those who received hydroxycarbamide was compared to that of untreated children. Among 1760 subjects, 267 received hydroxycarbamide at a median dose of 20•8 mg/kg/d (range 10-32) for a median of 2 years (range 0•1-6•5). Survival among hydroxycarbamide-treated children was significantly greater than that among untreated ones (99•5% vs. 94•5%, P = 0•01), due primarily to fewer deaths from acute chest syndrome and infection. Hydroxycarbamide therapy was significantly associated with increases in haemoglobin concentration, fetal haemoglobin, mean corpuscular volume, and reduction in platelet counts, reticulocytes and neutrophils. Toxicity was minimal and predominantly mild reversible neutropenia. Significantly fewer hospitalizations and emergency room visits, and shorter admissions were observed among hydroxycarbamide-treated subjects, when compared to the 12-month period prior to treatment initiation. Hydroxycarbamide therapy reduces disease severity and is probably associated with decreased mortality among children with SCD.
© 2013 John Wiley & Sons Ltd.
PMID: 23590693 [PubMed - as supplied by publisher]
10. Hemoglobin. 2013 Apr 17. [Epub ahead of print]
Maternal Complications and The Association with Baseline Variables in Pregnant Women with Sickle Cell Disease.
Al-Farsi SH, Al-Riyami NM, Al-Khabori MK, Al-Hunaini MN.
Department of Obstetrics and Gynaecology, Sultan Qaboos University Hospital , Muscat , Sultanate of Oman.
Sickle cell disease is an inherited hemoglobinopathy with multi system complications. It has been associated with multiple maternal complications. A retrospective review of 68 consecutive pregnant women with sickle cell disease, followed in a tertiary center, was conducted over 5 years, to estimate the incidence of different maternal complications and the impact of baseline characteristics. Sixty-eight patients were analyzed (mean age 30 years). Sixty-two patients had a Hb SS genotype. The initial mean hemoglobin (Hb) level was 9.5 g/dL. Twelve patients delivered by Cesarean section. Sixty-five patients required admission for sickle cell disease/pregnancy-related complications [96.0%; 95% confidence interval (95% CI) 91-100]. Infection was seen in 17 patients (25.0%, 95% CI 14-36). Blood transfusions were given to 61 patients (90.0%, 95% CI 82-97). Eight patients had gestational hypertension (18.0%, 95% CI 4-20), while five patients (7.0%, 95% CI 1-14) had pre term labor. One patient developed eclampsia and one had a uterine rupture. One patient died due to post partum hemorrhage. The multi variable logistic regression model on the impact on the major maternal complications revealed none of the baseline factors to be statistically significant. Sickle cell disease patients have low mortality and pregnancy-related morbidity but high sickle cell disease-related morbidity. Prospective studies are needed to confirm these results.
PMID: 23590330 [PubMed - as supplied by publisher]
11. ScientificWorldJournal. 2013 Mar 25;2013:694146. doi: 10.1155/2013/694146. Print 2013.
Biologic complexity in sickle cell disease: implications for developing targeted therapeutics.
Department of Pediatrics, Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA.
Current therapy for sickle cell disease (SCD) is limited to supportive treatment of complications, red blood cell transfusions, hydroxyurea, and stem cell transplantation. Difficulty in the translation of mechanistically based therapies may be the result of a reductionist approach focused on individual pathways, without having demonstrated their relative contribution to SCD complications. Many pathophysiologic processes in SCD are likely to interact simultaneously to contribute to acute vaso-occlusion or chronic vasculopathy. Applying concepts of systems biology and network medicine, models were developed to show relationships between the primary defect of sickle hemoglobin (Hb S) polymerization and the outcomes of acute pain and chronic vasculopathy. Pathophysiologic processes such as inflammation and oxidative stress are downstream by-products of Hb S polymerization, transduced through secondary pathways of hemolysis and vaso-occlusion. Pain, a common clinical trials endpoint, is also complex and may be influenced by factors outside of sickle cell polymerization and vascular occlusion. Future sickle cell research needs to better address the biologic complexity of both sickle cell disease and pain. The relevance of individual pathways to important sickle cell outcomes needs to be demonstrated in vivo before investing in expensive and labor-intensive clinical trials.
PMCID: PMC3621302 Free PMC Article
PMID: 23589705 [PubMed - in process]
12. J Pediatr Hematol Oncol. 2013 Apr 11. [Epub ahead of print]
Predictors for Bacteremia in Febrile Sickle Cell Disease Children in the Post-7-Valent Pneumococcal Conjugate Vaccine Era.
Chang TP, Kriengsoontorkij W, Chan LS, Wang VJ.
*Division of Emergency Medicine and Transport, Children's Hospital Los Angeles ‡Division of Biostatistics and Outcomes Assessment, Los Angeles County+University of Southern California Medical Center §Department of Pediatrics, Division of Research on Children, Youth, and Families, Keck School of Medicine of USC, Los Angeles, CA †Department of Pediatrics, Siriraj Hospital/Mahidol University, Bangkok, Thailand.
OBJECTIVES: The objective of this study was to determine the incidence of bacteremia in febrile sickle cell disease (SCD) children before and after the 7-valent pneumococcal vaccine (PCV7), and to determine clinical factors associated with bacteremia following PCV7. PATIENTS AND METHODS:: We reviewed all febrile events in SCD children from 1993 to 2009 at a tertiary care pediatric center, comparing general bacteremia and pneumococcal bacteremia incidence for 3 time periods around the PCV7. Univariate analysis and stepwise logistic regression identified clinical factors most associated with bacteremia in this population. RESULTS:: Of 466 SCD children identified, there were 2504 febrile events. We found 84 cases of bacteremia; 8 were pneumococcal. The general bacteremia incidence decreased significantly from 5.60% to 2.44% (P<0.001) over time. Pneumococcal bacteremia incidence did not decrease (P=0.13). Following PCV7, we identified 4 significant independent risk factors associated with general bacteremia: the presence of a central venous line, higher absolute band count, toxic appearance, and older age. CONCLUSIONS:: In febrile SCD children, the incidence of general bacteremia decreased over time. No decrease in pneumococcal bacteremia was found. The presence of a central venous line, absolute band count, clinical appearance, and age may help predict bacteremia in this population.
PMID: 23588338 [PubMed - as supplied by publisher]
13. Am J Med. 2013 May;126(5):443-9. doi: 10.1016/j.amjmed.2012.12.016.
Venous Thromboembolism in Adults with Sickle Cell Disease: A Serious and Under-recognized Complication.
Naik RP, Streiff MB, Haywood C Jr, Nelson JA, Lanzkron S.
Department of Medicine, Division of Hematology, Johns Hopkins University, Baltimore, Md. Electronic address: email@example.com.
Sickle cell disease is recognized as a hypercoagulable state; however, the frequency and characteristics of venous thromboembolism in sickle cell patients have not been well defined. The purpose of this study was to establish the prevalence and risk factors for venous thromboembolism in a large cohort of patients with sickle cell disease and determine the relationship between venous thromboembolism and mortality.
We performed a cross-sectional study of 404 sickle cell disease patients cared for at the Sickle Cell Center for Adults at Johns Hopkins. Demographic, sickle cell disease-specific comorbidity, and venous thromboembolism data were collected on all patients.
One hundred one patients (25%) had a history of venous thromboembolism with a median age at diagnosis of 29.9 years. A history of non-catheter-related venous thromboembolism was found in 18.8% of patients. Sickle variant genotypes conferred a higher risk of non-catheter-related venous thromboembolism compared with sickle cell anemia genotypes (SS/Sβ(0)) (relative risk [RR] 1.77; 95% confidence interval [CI], 1.18-2.66). Tricuspid regurgitant jet velocity ≥2.5 m/s also was associated with non-catheter-related venous thromboembolism (RR 1.65; 95% CI, 1.12-2.45). Thirty patients (7.4%) died during the study period. Adjusting for all variables, non-catheter-related venous thromboembolism was independently correlated with death (RR 3.63; 95% CI, 1.66-7.92).
Venous thromboembolism is common in adults with sickle cell disease. Sickle variant genotypes and tricuspid regurgitant jet velocity ≥2.5 m/s are associated with non-catheter-related venous thromboembolism. In addition, non-catheter-related venous thromboembolism appears to be an independent risk factor for death in our cohort. These results suggest that disease-specific prophylaxis and treatment strategies for venous thromboembolism should be investigated in sickle cell disease patients.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMCID: PMC3627211 [Available on 2014/5/1]
PMID: 23582935 [PubMed - in process]
14. Stem Cells Transl Med. 2013 Apr 11. [Epub ahead of print]
Umbilical Cord Blood: An Evolving Stem Cell Source for Sickle Cell Disease Transplants.
Division of Pediatric Hematology/Oncology, Washington University, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Allogeneic hematopoietic stem cell transplantation has proven benefit in controlling sickle cell disease-related vasculopathy and organ damage. Myeloablative matched sibling donor cord transplants have excellent outcomes in sickle cell disease. Unrelated donor transplant options are often deferred because of a lack of suitable human leukocyte antigen-matched donors, a problem especially relevant to minority populations. Umbilical cord blood transplantation allows for more mismatching from the graft-versus-host disease perspective and the donor pool is expandable with effort and education. Drawbacks such as increased rates of graft rejection, a fixed cell dose, delayed immune reconstitution, and transplant-related mortality have deterred unrelated cord transplant efforts. However, the transplant community continues to make enormous strides in this transplant realm in areas of immunogenetics, stem cell expansion, conditioning regimens, and supportive care. This has allowed the development of new studies that are currently ongoing, exploring ways to make cord blood transplantation successful and safer. The goal is to make unrelated donor cord blood transplantation for sickle cell disease merit early consideration in patients who stand to benefit from this approach.
PMID: 23580541 [PubMed - as supplied by publisher]
15. Clin Nurs Res. 2013 Apr 8. [Epub ahead of print]
Evaluation of the SCKnowIQ Tool and Reproductive CHOICES Intervention Among Young Adults With Sickle Cell Disease or Sickle Cell Trait.
Gallo AM, Wilkie DJ, Wang E, Labotka RJ, Molokie RE, Stahl C, Hershberger PE, Zhao Z, Suarez ML, Johnson B, Pullum C, Angulo R, Thompson A.
University of Illinois at Chicago, College of Nursing, Department of Women, Children and Family Health Science, Chicago, IL, USA.
The study purpose was to evaluate a computer-based questionnaire (SCKnowIQ) and CHOICES educational intervention using cognitive interviewing with childbearing-aged people with sickle cell disease (SCD) or trait (SCT). Ten control group participants completed the SCKnowIQ twice. Ten intervention group participants completed the SCKnowIQ before and after the CHOICES intervention. Most participants found the questionnaire items appropriate and responded to items as the investigators intended. Participants' responses indicated that the information on SCD and SCT and reproductive options was understandable, balanced, important, and new to some. Internal consistency and test-retest reliability were adequate (.47 to .87) for 4 of the 6 scales, with significant within-group changes in knowledge scores for the intervention group but not for the control group. Findings show evidence for potential efficacy of the intervention, but proof of efficacy requires a larger randomized study.
PMID: 23572406 [PubMed - as supplied by publisher]
16. Pediatr Hematol Oncol. 2013 Apr 9. [Epub ahead of print]
Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease.
Patel A, Zuzo A, Imran H, Siddiqui AH.
University of South Alabama College of Medicine , Mobile, Alabama , USA.
We performed a retrospective chart review of children with sickle cell disease hospitalized for fever at our local institution. We reviewed 456 hospitalizations in 133 patients between January 2006 and June 2012. The prevalence of true bacteremia was 4%. The mean C-reactive protein values and temperatures were nonsignificantly higher in patients with positive blood cultures. The mean time to detection was 22.5 hours in bacteremia compared to 32.6 hours in blood cultures that grew contaminants (p = .034). Only two (0.4%) cases of pneumococcal bacteremia were reported and both occurred before May 2010, which marks the introduction of 13-valent pneumococcal vaccine (PCV13). Both patients with pneumococcal bacteremia had discontinued penicillin prophylaxis after the age of 5 years. The first patient was immunized but contracted a nonvaccine serotype (23B). The second patient was partially vaccinated and acquired a vaccine-preventable serotype (23F). Both serotypes were sensitive to ceftriaxone and vancomycin; one was resistant to penicillin. This is the first study reporting the prevalence of pneumococcal bacteremia since the introduction of PCV13.
PMID: 23570543 [PubMed - as supplied by publisher]
17. Ann Emerg Med. 2013 Apr 2. pii: S0196-0644(13)00108-X. doi: 10.1016/j.annemergmed.2013.02.004. [Epub ahead of print]
Emergency Provider Analgesic Practices and Attitudes Toward Patients With Sickle Cell Disease.
Glassberg JA, Tanabe P, Chow A, Harper K, Haywood C Jr, Debaun MR, Richardson LD.
Department of Emergency Medicine, Mount Sinai School of Medicine, New York, NY. Electronic address: firstname.lastname@example.org.
We determine whether emergency provider attitudes and demographics are associated with adherence to national guidelines for the management of acute sickle cell disease pain.
We conducted a cross-sectional survey of emergency providers at the 2011 annual American College of Emergency Physicians Scientific Assembly, using a validated instrument to assess provider attitudes and self-reported analgesic practices toward patients with sickle cell disease. Multivariable, relative risk regressions were used to identify factors associated with adherence to guidelines.
There were 722 eligible participants, with a 93% complete response rate. Most providers self-reported adherence to the cornerstones of sickle cell disease pain management, including parenteral opioids (90%) and redosing opioids within 30 minutes if analgesia is inadequate (85%). Self-reported adherence was lower for other recommendations, including use of patient-controlled analgesia, acetaminophen, non-steroidal anti-inflammatory drugs and hypotonic fluids for euvolemic patients. Emergency providers in the highest quartile of negative attitudes were 20% less likely to redose opioids within 30 minutes for inadequate analgesia (risk ratio 0.8; 95% confidence interval [CI] 0.7 to 0.9). High-volume providers (those who treat more than 1 sickle cell disease patient per week), were less likely to redose opioids within 30 minutes for inadequate analgesia (risk ratio 0.9; 95% CI 0.8 to 0.9). Pediatric providers were 6.6 times more likely to use patient-controlled analgesia for analgesia (95% CI 2.6 to 16.6).
The majority of emergency providers report that they adhere to national guidelines about use of opioids for sickle cell disease-related acute pain episodes. Other recommendations have less penetration. Negative attitudes toward individuals with sickle cell disease are associated with lower adherence to guidelines.
Copyright © 2013. Published by Mosby, Inc.
PMID: 23561465 [PubMed - as supplied by publisher]
Sickle Cell News for August 2012
September is Sickle Cell Month – see all the events at the end of the newsletter
Living Well with Sickle Cell
Forty-eight-year-old Ayoola Olajide is living well with sickle cell anaemia (SS). Olajide, the Editor of African Sickle Cell News and World Report, and author of Menace In My Blood- my affliction with sickle cell anaemia is married to a woman with the AA genotype (without the SS trait) and they have three boys (AS, without anaemia but are carriers). Olajide, a journalist, is on a crusade to address the genetic disorder through aggressive public enlightenment.. He said Nigerians with sickle cell could live well into old age if they have the right information and others could avoid having children with the condition by making the right choices. http://www.ngrguardiannews.com/index.php?option=com_content&view=article&id=96379:living-well-with-sickle-cell-anaemia-for-48-years&catid=44:natural-health&Itemid=599
Affordable Care Act (ACA) by the United States Supreme Court - SCDAA Summary at http://www.sicklecelldisease.org/index.cfm?page=chief-medical-officer-news
The Sickle Cell Disease Association of America, Inc. (SCDAA) applauds the upholding of many of the provisions of the Affordable Care Act (ACA) by the United States Supreme Court. The ACA represents a significant victory for individuals with chronic diseases such as sickle cell disease. Fear of moving from your pediatric doctor to an adult doctor because you may not have insurance may be unnecessary under the ACA.
How does the ACA protect you as an individual living with sickle cell disease? SCDAA wants to point out how ACA can improve the healthcare of people with sickle cell disease.
What does this mean? This means that health insurance companies cannot deny coverage to anyone with a chronic health condition such as sickle cell disease. Furthermore, your health insurance company can no longer set a limit on how much of your health care costs they will pay forever, this is known as "lifetime cap". Currently, the limit on how much they will pay for your heath care in each year has been set at $750,000. The long-term goal of ACA is to eliminate annual limits that are currently practiced by insurance companies from imposing any annual limits at all. SCDAA will closely monitor and report to you and our member organizations as to the progress the ACA law makes in removing these annual limits completely.
New CDC Videos Posted
Translating Research to Policy Dr. Shawn Bediako, University of Maryland, Baltimore County at mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCBediako.wmv
Schedule of Free CDC 2012 Webinars
“Public Health Webinar Series on Hemoglobinopathies”
Hosted by: The Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC) 4th Thursday of every month from 2:00PM – 3:00PM ET The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.
Hemoglobinopathy Webinars are archived at http://scinfo.org
To Join The Webinar
Copy this address and paste it into your web browser: https://www.livemeeting.com/cc/cdc/join
Copy and paste the required meeting ID: 84QK2D and click “join”.
First Time Users: To save time before the meeting, check your system to make sure it is ready to use Microsoft Office Live Meeting. To hear the presentation you must call in to the number below.
Dial 1-877-953-6706 and enter participant code: 9706616
If you are unable to join us on the internet for viewing, you are welcome to call in for audio access only. Participants outside the United States must be able to access 800 numbers to the US. Otherwise, please RSVP the location and number of participants for alternative international conference line access.
9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center
10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States
November/December: --- No Webinars---
See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see: http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health
New Web Resource
NHS Sickle Cell and Thalassaemia Screening Programme Training Modules
Standards are key in the delivery of an expert antenatal and newborn screening programme. The NHS Sickle Cell and Thalassaemia Screening Programme has invested in a laboratory module where laboratory personnel can participate in online training which tests them on the basic heterozygous conditions which must be detected by the antenatal screening programme.
The module has been designed to incorporate the standards of the Screening Programme’s Laboratory Handbook
See all the publications at http://sct.screening.nhs.uk/
Articles in the Medical Literature for August
Br J Haematol. 2012 Aug 28. doi: 10.1111/bjh.12019. [Epub ahead of print]
Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
© 2012 Blackwell Publishing Ltd.
PMID: 22924607 [PubMed - as supplied by publisher]
ScientificWorldJournal. 2012;2012:949535. Epub 2012 Aug 1.
Cardeza Foundation and Department of Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA.
The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.
PMCID: PMC3415156 Free Article
PMID: 22924029 [PubMed - in process]
Blood. 2012 Aug 24. [Epub ahead of print]
Cardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadephia, PA, United States;
Sickle cell pain includes three types: acute recurrent painful crises, chronic pain syndromes and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the Emergency Department. It evolves through four phases: prodromal, initial, established and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage such as acute chest syndrome, multi-organ failure and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other non-sickle pain syndromes.
PMID: 22923496 [PubMed - as supplied by publisher]
Chest. 2012 Aug 20. doi: 10.1378/chest.12-0611. [Epub ahead of print]
Little is known about pulmonary vascular complications in children with Sickle Cell Disease (SCD). We hypothesised that transfer factor (DLco) may be used as a surrogate for the size of the pulmonary vascular bed, and that pulmonary vascular abnormalities in SCD children may limit exercise capacity.
50 stable SCD patients aged10 to-18 years and 50 healthy controls matched for race and age were recruited. Incremental ergometer cardiopulmonary exercise testing (CPET) was performed using respiratory mass spectrometry (RMS) for exhaled gas analysis. A rebreathing manoeuvre was used to measure functional residual capacity (FRC), effective pulmonary blood flow (Qpeff) and DLCO, and helium dilution was used to calculate minute ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (CO2).
In the 89 evaluable subjects, there were no ventilatory differences between SCD and controls. Qpeff was consistently 15-20% greater in SCD than controls at all stages but Dlco corrected for both surface area and haemoglobin was only about 7-10% greater in SCD at all stages As a result the Dlco/Qpeff ratio was considerably lower in SCD at all stages. Arteriovenous oxygen content difference was about one third less in SCD at all stages.
Contrary to our hypothesis, failure to maintain a sufficient Qpeff to compensate for anaemia led to exercise limitation. The ratio of Pulmonary capillary blood volume to flow is reduced throughout, implying subtle pulmonary vascular disease; however this was not a factor limiting exercise.1Royal Brompton Hospital, London, United Kingdom.2St Georges' Hospital, London, United Kingdom.Corresponding author's details (also author for reprint requests): Dr Mark Rosenthal, Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London SW3 6NP Email: M. Rosenthal@rbht.nhs.uk.
PMID: 22922408 [PubMed - as supplied by publisher]
Blood. 2012 Aug 22. [Epub ahead of print]
Duke University Medical Center, Durham, NC, United States;
BABY HUG was a Phase III multicenter, randomized, double-blind placebo-controlled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia (SCA). An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninety-three subjects were randomized to hydroxyurea (20 mg/kg/day) or placebo; there were 374 patient-years of on-study observation. Hydroxyurea was associated with statistically significantly lower rates of initial and recurrent episodes of pain, dactylitis, ACS and hospitalization; even infants who were asymptomatic at enrollment had less dactylitis as well as fewer hospitalizations and transfusions if treated with hydroxyurea. Despite expected mild myelosuppression, hydroxyurea was not associated with an increased risk of bacteremia or serious infection. These data provide important safety and efficacy information for clinicians considering hydroxyurea therapy for very young children with SCA. This clinical trial is registered with the NIH (NCT00006400, www.clinicaltrials.gov).
PMID: 22915643 [PubMed - as supplied by publisher]
Adv Skin Wound Care. 2012 Sep;25(9):420-428.
Barry Ladizinski, MD, BS • Clinical Research Fellow • Duke University Medical Center • Durham, North Carolina Andrea Bazakas, BS • Clinical Trials Assistant II • Duke University Medical Center • Durham, North Carolina Nisha Mistry, MD, BSc, FRCPC(Derm), DABD • Community Dermatologist • Mississauga, Ontario, Canada Afsaneh Alavi, MD, FRCPC(Derm) • Dermatologist and Wound Care Consultant • Women's College Hospital • Toronto, Ontario, Canada R. Gary Sibbald, BSc, MD, Med, FRCPC(Med Derm), MACP, FAAD, MAPWCA • Professor of Public Health and Medicine • University of Toronto • Toronto, Ontario, Canada • Director • International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care) • Dalla Lana School of Public Health • University of Toronto • President World Union of Wound Healing Societies • Clinical Editor • Advances in Skin & Wound Care • Ambler, Pennsylvania Richard Salcido, MD • Editor-in-Chief • Advances in Skin & Wound Care • Ambler, Pennsylvania • Course Director • Annual Clinical Symposium on Advances in Skin & Wound Care • William Erdman Professor • Department of Rehabilitation Medicine • Senior Fellow • Institute on Aging • Associate • Institute of Medicine and Bioengineering • University of Pennsylvania Health System • Philadelphia, Pennsylvania.
PURPOSE:: To enhance the learner's competence with knowledge of sickle cell disease (SCD) and its relationship to leg ulcers. TARGET AUDIENCE:: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES:: After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of SCD-associated leg ulcer pathophysiology, symptomatology, diagnostic testing, and risk factors.2. Apply knowledge of pain management and treatment options for SCD-associated leg ulcers to patient care scenarios. ABSTRACT: Sickle cell disease is a genetic disorder of hemoglobin synthesis leading to a deformation of the red blood cell. This disorder is associated with painful, slow-to-heal leg ulcers. This article discusses the wound bed preparation paradigm as a guide to the treatment of sickle cell-associated leg ulcers.
PMID: 22914039 [PubMed - as supplied by publisher]
J Urol. 2012 Aug 16. [Epub ahead of print]
Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil.
We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease.
This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations.
The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index.
Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.
Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID: 22902014 [PubMed - as supplied by publisher]
Cell Host Microbe. 2012 Aug 16;12(2):187-99.
The Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; University Program in Genetics and Genomics, Duke University School of Medicine, Durham, NC 27710, USA.
Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22901539 [PubMed - in process]
Clin Biochem. 2012 Aug 8. [Epub ahead of print]
Assistance publique-hôpitaux de Paris, Hôpital Tenon, Service de médecine interne, Centre de référence de la drépanocytose adulte, Paris, France.
The aim of this study is to assess biological prognostic factors at the onset of vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD).
A monocentric prospective study including all patients admitted for VOC in a reference center for SCD was utilized. We used multivariate logistic regression to find independent predictors of severe evolution, defined by death or a worsening clinical state indicating transfusion or transfer to the intensive care unit.
Eighty eight patients were included, 63% were women, median age of 23years, and 90% of patients were homozygous SCD, 10% compound heterozygous. VOC became severe in 17 patients. Patients with severe VOC were more frequently males, who also had higher white blood cell (WBC) count, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels. LDH level was the best predictor of the outcome; WBC and PCT had no significant added predictive values when coupled with LDH in multivariable models, even in patients with fever or acute chest syndrome. Severe evolution always occurred when LDH levels were over 4 times the upper limit of the normal range at admission and never occurred when LDH levels were within the normal range.
Further studies should confirm the predictive value of LDH before its widespread use as a prognostic factor. If it is confirmed, the benefit of preemptive transfusion when LDH levels at admission are very high could be investigated.
Copyright © 2012. Published by Elsevier Inc.
Sickle Cell Conferences and Events
September 25 – 29, 2012 The Sickle Cell Disease Association of America 40th Annual Conference Baltimore MD
The conference will be held September 25 – 29, 2012 at the Baltimore Marriott Waterfront Hotel in Baltimore, MD. We promise that this will be one of the most educational and empowering events to take place within the sickle cell community! http://www.sicklecelldisease.org/index.cfm?page=annual-convention
24-27 September Annual Sickle Cell and Thalassaemia: Advanced Conference -, London UK. The programme will provide participants with an overview of the key issues in sickle cell disease including a look at the pathology of SCD, diagnostic testing, the impact of environmental factors and genetic modifiers on disease severity, managing acute and chronic sickle cell crises, and dealing with major complications in patients including stroke, renal, liver and cardiac problems and the treatment options available. Website is: http://www.guysandstthomasevents.co.uk
The main Guy’s and St Thomas’ NHS Foundation Trust website is: www.guysandstthomas.nhs.uk
September 19, 2012 NYC, NY 1st Annual Sickle Cell Disease Therapeutics Conference. The conference is intended to serve as a forum to raise awareness for sickle cell disease and will include presentations from leading companies in sickle cell disease and discussions with experts regarding the latest advancements and future trends for patients. The conference will be held September 19, 2012 in the Cosmopolitan Suite at the Four Seasons Hotel in New York City. Conference sponsors include Theradex Systems, Inc. and Rodman & Renshaw, LLC.
Conference attendees will hear from leaders in the sickle cell disease medical and advocacy communities More information can be found on the conference web site at http://www.scdconference.com or on the advertising flyer for the event at http://www.scdconference.com/wp-content/uploads/2012/07/SCDTC_InformationPage.pdf
SICKLE CELL ASSOCIATION OF ONTARIO ANNUAL CONFERENCETo be held on September 28th and 29th 2012 at the Toronto Delta East Hotel
The Sickle Cell Association of Ontario's mission is to serve the community as a recognized voluntary agency that endeavors to optimize the quality of life for individuals and families with sickle cell disease.
The Sickle Cell Association of Ontario (SCAO) is a non-profit charitable organization, established in 1981 after it became evident that there was a need to educate the public about sickle cell anemia. Also, to provide moral support to parents and families of children, spouses, other relatives and individuals who suffer from sickle cell anemia.
Sickle Cell Association of Ontario 416 789 2855 Tel 416 789 1903 Fax email email@example.com
Stephanie Mulkey Annual Sickle Cell Disease Educational Seminar, taking place this September 7 and 8 at the Wallis Annenberg building in Exposition Park, Los Angeles, CA, is available online (click here: http://events.r20.constantcontact.com/register/event?oeidk=a07e68bp0fba5aaa453&llr=7fy6tgdab).
For Adults Only with Sickle Cell Disease Workshop - Atlanta GA
Date/Time: September 22, 2012 9am - 3pm
Location: Adamsville Recreation Center, 3201 Martin Luther King Jr., Drive, Atlanta 30311
September is National Sickle Cell Disease Awareness Month, and in an effort to raise awareness and educate adults living with the disease, a free, one-day workshop is being held on Saturday, September 22, 2012 from 9:00 a.m. - 3:00 p.m. at the Adamsville Recreation Center in Atlanta, GA.
Sponsored by Georgia Department of Public Health, Sickle Cell Foundation of Georgia, SPCC Atlanta AHEC, and the Georgia Health Policy Center, this workshop is limited to adult sickle cell patients living in the state of Georgia. Attendees may be accompanied by a care giver or significant other, however, we will not be able to accommodate children.Participants will hear from healthcare professionals specializing in sickle cell disease as well as people living with the disease. In addition, community resources will be available for workshop participants as well.
For more information, call 404-815-4996. To register for the workshop, go to http://sicklecelladultworkshop.eventbrite.com/.
Complimentary continental breakfast and lunch will be provided
West Coast Sickle Cell Nurses Conference Friday, October 26, 2012 Presented by
Children's Hospital Los Angeles -Improving Outcomes for Children and Adults
with Sickle Cell Disease Location: John Stauffer Conference Room Children's Hospital Los Angeles Registration fee: $45.00 5 CEU's Lunch provided
Please note, this is a NURSES ONLY conference.
For adults and parents, please provide this information to your nurse or health care provider. For more information, contact Trish Peterson at firstname.lastname@example.org
or Debbie Harris at email@example.com
the Cuban Society of Hematology VII National Congress for the Spring of 2013 (May 20-24) at the Havana International Conference Center, under the name of HEMATOLOGIA 2013. Toghether with this event, we will be celebrating the III Caribbean Conference on Sickle Cell Disease (from CAREST), as well as the IX Latinamerican Meeting on Hematology, Immunology and Transfusion Medicine, the IV International Workshop on Hemophilia, and the III Internatioal Symposium of Regenerative Medicine.
Sickle Cell Anemia research is constantly ongoing. As information becomes available, it will be posted at this location, it can be found at the Cleveland Clinic web site, or you can contact Ira Bragg-Grant at (216) 229-8600 for the latest available research information as it occurs.
For the latest news, visit this website that is updated weekly at www.scinfo.org/news.htm
In the News
Events around the world include:
On behalf of the National Heart, Lung, and Blood Institute (NHLBI), we would like to share with you news about a sickle cell disease clinical trial, the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) study. The multicenter clinical trial compared treatments to reduce the risk of additional strokes while minimizing the adverse effects of treatment such as iron overload in young participants (between the ages of 5 and 19) with sickle cell disease and a history of stroke and iron overload. The study was stopped early because a regular review of the data indicated that the experimental treatment was unlikely to prove better than the standard treatment. The NHLBI issued a press release about the early termination of the study, which can be found at: http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2709.
The preliminary results of this study support the use of the standard treatment of periodic blood transfusions for reducing the risk of additional strokes in young, high-risk patients combined with deferasirox (EXJADE®), an FDA-approved drug to treat chronic iron overload. The alternative treatment that was tested -- hydroxyurea combined with phlebotomy -- does not appear to be better than this standard treatment.
Protecting study participants is the NHLBI’s priority, and when an experimental treatment fails to meet its predetermined goals, it is best to return participants to standard treatment as soon as possible. The NHLBI remains committed to continuing to support research to identify new or improved ways to reduce the burden of sickle cell anemia’s most severe symptoms on our children.
The results from SWiTCH do not affect the majority of sickle cell disease patients who are currently benefiting from hydroxyurea. NHLBI-supported research has shown that hydroxyurea helps prevent pain crises and some lung complications in adults. Patients currently taking hydroxyurea should continue taking the treatment as prescribed and should talk to their primary care provider if they have any concerns. Please let us know if you have any questions about the study. For scientific questions, please contact W. Keith Hoots, M.D., director of the NHLBI Division of Blood Diseases and Resources, at 301-435-0080.
This book provides a transparent look into my personal struggle with sickle cell disease and how it led me to the formation of SCD Soldier Network, Inc. I co-authored the book with Atlanta Historian Dan Moore of the Apex Museum and founder of Marrow for Life. The book also includes the inspiring stories of others who battle the disease as well as it gives you the history of sickle cell and information about the blood disorder. I am very pleased with this project and am asking for your support. Please purchase your copy today, I promise you won't be disappointed. Please see attached flyer or access the website to purchase the book by clicking on the link www.createspace.com/3458126 Fifty percent of the proceeds from the sale of this book will be donated to SCD Soldier Network in order to fulfill it's mission.
Articles in the Medical Literature
Raphael JL, Shetty PB, Liu H, Mahoney DH, Mueller BU. A critical assessment of transcranial doppler screening rates in a large pediatric sickle cell center: opportunities to improve healthcare quality. Pediatr Blood Cancer. 2008 Nov;51(5):647-51. http://www.ncbi.nlm.nih.gov/pubmed/18623200?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Wang WC, Pavlakis SG, Helton KJ, McKinstry RC, Casella JF, Adams RJ, Rees RC; BABY HUG Investigators. MRI abnormalities of the brain in one-year-old children with sickle cell anemia. Pediatr Blood Cancer. 2008 Nov;51(5):643-6. http://www.ncbi.nlm.nih.gov/pubmed/18478575?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Moreira-Almeida A, Koenig HG. Religiousness and spirituality in fibromyalgia and chronic pain patients. Curr Pain Headache Rep. 2008 Oct;12(5):327-32. http://www.ncbi.nlm.nih.gov/pubmed/18765136?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Okumura MJ, Heisler M, Davis MM, Cabana MD, Demonner S, Kerr EA. Comfort of general internists and general pediatricians in providing care for young adults with chronic illnesses of childhood. J Gen Intern Med. 2008 Oct;23(10):1621-7. Epub 2008 Jul 26. http://www.ncbi.nlm.nih.gov/pubmed/18661191?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Sonati MD, Costa FF. The genetics of blood disorders: the hereditary hemoglobinopathies. J Pediatr (Rio J). 2008 Sep 12;84(4 (Suppl)). Full Text PDF http://www.jped.com.br/conteudo/AA_12908_A01/ing.pdf
Gold JI, Mahrer NE, Treadwell M, Weissman L, Vichinsky E. Psychosocial and behavioral outcomes in children with sickle cell disease and their healthy siblings. J Behav Med. 2008 Sep 11. http://www.ncbi.nlm.nih.gov/pubmed/18784995?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Mittal H, Roberts L, Fuller GW, O'Driscoll S, Dick MC, Height SE, Thein SL, Rees DC. The effects of air quality on haematological and clinical parameters in children with sickle cell anaemia. Ann Hematol. 2008 Sep 4. http://www.ncbi.nlm.nih.gov/pubmed/18769920?ordinalpos=19&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Ulug P, Vasavda N, Kumar R, Keir L, Awogbade M, Cunningham J, Rees DC, Menzel S, Thein SL. Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia. Am J Hematol. 2008 Sep;83(9):714-6. http://www.ncbi.nlm.nih.gov/pubmed/18615556?ordinalpos=21&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Koch J, Manworren R, Clark L, Quinn CT, Buchanan GR, Rogers ZR. Pilot study of continuous co-infusion of morphine and naloxone in children with sickle cell pain crisis. Am J Hematol. 2008 Sep;83(9):728-31. http://www.ncbi.nlm.nih.gov/pubmed/18543345?ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Rovner AJ, Stallings VA, Kawchak DA, Schall JI, Ohene-Frempong K, Zemel BS. High risk of vitamin d deficiency in children with sickle cell disease. J Am Diet Assoc. 2008 Sep;108(9):1512-6. http://www.ncbi.nlm.nih.gov/pubmed/18543345?ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Palermo TM, Riley CA, Mitchell BA. Daily functioning and quality of life in children with sickle cell disease pain: relationship with family and neighborhood socioeconomic distress. J Pain. 2008 Sep;9(9):833-40. Epub 2008 Jun 12. http://www.ncbi.nlm.nih.gov/pubmed/18550443?ordinalpos=35&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Ask the Experts
Is delayed puberty an issue for sickle cell patients?
Delayed growth & delayed puberty are very common features of sickle cell disease. Poor nutrition may make the delay worse, and a nutrition consultation may be helpful. A few centers use supplements of growth hormone or testosterone to help with growth, but decisions to use those hormones need a detailed assessment by a pediatric endocrinologist. Anti-sickling therapy with hydroxyurea or chronic transfusion are likely to help with growth. Bone marrow transplantation has complex effects on growth and puberty. I encourage you to discuss these inter-related issues with your son's hematologist, endocrinologist, and nutritionist
Here is the abstract of one recent journal article on this topic.
Pediatr Res. 2007 May;61(5 Pt 1):607-13.
Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease.
Zemel BS, Kawchak DA, Ohene-Frempong K, Schall JI, Stallings VA.
Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. firstname.lastname@example.org
Previous studies of children with sickle cell disease (SCD) reported poor growth and delayed maturation. However, the prevalence, magnitude, and correlates of suboptimal growth remain poorly understood. A prospective longitudinal study was undertaken to determine the effects of disease severity and nutritional status on growth, an indicator of childhood well-being. Children, birth to 18 y of age, with SCD-SS were evaluated annually for 4 y. Growth, nutritional status, skeletal and sexual maturation, disease severity, dietary intake, and maternal education were assessed. In this sample of 148 children (78 females), growth in height, weight, or body mass index declined in 84% of subjects; 38% fell below the 5th percentile in one or more measures. Puberty was delayed 1 to 2 y, and median age at menarche was 13.2 y. Skeletal age was delayed by 0.7 +/- 1.4 y overall and by 1.3 +/- 1.5 y in children 10 to 15 y old. Height status declined over time and was positively associated with advancing puberty and hematological measures in girls, and nutritional status in girls and boys. Growth failure and maturational delay remain significant chronic problems in children with SCD-SS and are related to potentially modifiable factors such as nutritional status.
Lewis Hsu, MD, PhD
For more frequently asked questions please see: http://www.scinfo.org/faq.htm
American Society of Hematology Launches New Campaign to Educate Consumers on Vital Connection Between Blood and Personal Health http://www.bloodthevitalconnection.org/
Program developed in response to results of national survey indicating most Americans have low awareness of common blood conditions
Dr. Charles Whitten, M.D., associate dean emeritus of the Wayne State University School of Medicine, died Aug. 13. He was 86.
“Dr. Whitten was a pioneer in the field of medical education,” said Robert Frank, M.D., executive vice dean for the School of Medicine. “He founded the post baccalaureate program at Wayne State University School of Medicine, which was a national model for the inclusion of under-represented minority students in schools of medicine. Dr. Whitten revolutionized the curriculum at our School of Medicine, and was a personal mentor to many of our current medical educators.”
The post baccalaureate program led to Wayne State University leading the nation’s 125 medical schools (exclusive of Howard and Meharry) in the total number of African-American graduates from 1981 to 1997. One-third of them had entered through his program.
In addition to developing the post baccalaureate program in 1969, Dr. Whitten formed the Sickle Cell Detection and Information Center, the most comprehensive community program in the country, and facilitated the creation of the National Association for Sickle Cell Disease.
As chief of Pediatrics at Detroit Receiving Hospital, he was the first African-American physician to head a department in a Detroit hospital.
Dr. Whitten, who served more than 40 years as a member of the School of Medicine faculty, served 16 years as associate dean for Curriculum before entering semi-retirement in 1993 as professor and dean emeritus.
“Dr. Whitten was best known for his pioneering work in sickle cell anemia screening and development of novel educational tools for teaching children and families with sickle cell anemia,” said Yaddanapudi Ravindranath, M.B.B.S., professor of Pediatrics and the Georgie Ginopolis Chair for Pediatric Cancer and Hematology at the School of Medicine, and co-director of the Division of Hematology/Oncology for Children's Hospital of Michigan. “His forceful advocacy paved the way for the routine newborn screening for sickle cell anemia in Michigan and later in the United States.”
Bio at http://www.med.umich.edu/haahc/Oralbios/whitten.htm
Ask the Experts
I can not afford the medications prescribed for me, Are there ant programs that can help?
There are some very good programs that help such as
http://www.needymeds.com/ http://www.rxassist.org/ https://www.pparx.org/Intro.php
Work with your clinician to see if these programs can help
Which is better erythrocytopheresis or simple blood transfusion for the prevention of childhood stroke?
Nobody has hard data on the number of sickle cell patients in the USA, but the estimate from the Sickle Cell Disease Association of America is 100,000. The estimate is that 10% of the children with sickle cell disease SS are at risk for stroke and will benefit from chronic transfusion as primary or secondary stroke prevention.
Some studies comparing costs of chronic simple transfusion plus iron chelation vs bone marrow transplant also include erythrocytapheresis. The costs depend fairly strongly on whether the target HbS is 30percent or 50 percent.
As you know, the use of RBC exchange is far better than simple transfusion in terms of iron overload but requires technical expertise and a good cost structure. When I was practicing in Atlanta, we wrote numerous business plans about setting up sickle cell erythrocytapheresis centers for the many pediatric sickle cell patients. The limiting factors were:
1) nursing expertise for venous access. Some children requiring erythrocytapheresis may be as young as 2yrs. Not every patient can maintain an indwelling catheter for pheresis, often they get infected or clotted. The pheresis service needs superb nurses who can place a large-bore peripheral IV in any patient.
2) most insurance companies paid the same amount for erythrocytapheresis as for a simple blood transfusion - which covered costs for neither but was much less favorable from a financial perspective for erythrocytapheresis.
3) greater demand for specially matched PRBC (negative for C, E, Kell antigens and negative for sickle hemoglobin) would strain the Blood Bank supply. Many pheresis units require partnering with a special donor recruitment programs to increase blood donations by African-Americans who are more likely than Caucasians to have RBC that are negative for C, E, Kell. The PRBC demand depends fairly strongly on whether the target HbS is 30percent or 50 percent.
My impression is that medical centers offering erythrocytapheresis combine it somehow with hemodialysis units or some other service to help break even. Or the medical centers just eat the cost because it is better for the patients and perhaps feature this service as a marketing tool.
Dr. Hae-won Kim at Children's Hospital of Philadelphia has the largest erythrocytapheresis center for sickle cell patients that I have seen. She taught many centers how to set up sickle cell erythrocytapheresis.
Lewis Hsu, MD, PhD
For more frequently asked questions please see: http://www.scinfo.org/faq.htm
Gaining Ground On Sickle Cell Disease. - Children's Hospital Boston (2008, July 16). ScienceDaily. Retrieved July 17, 2008, from http://www.sciencedaily.com/releases/2008/07/080715132723.htm
Although sickle cell disease is a single-gene disorder, its symptoms are highly variable. In a study published online July 14 by the Proceedings of the National Academy of Sciences, scientists at Children's Hospital Boston and the Dana Farber Cancer Institute (DFCI), in collaboration with the Broad Institute of MIT and Harvard, report five gene variants that could potentially be helpful in predicting sickle cell disease severity, perhaps even leading to better treatment approaches in the future. The gene variants influence blood levels of fetal hemoglobin (HbF), which are known to affect symptom severity in sickle cell disease--with some patients experiencing frequent, severe pain crises and organ damage, while others are scarcely aware of their disease.
"Our study is a first step towards a better understanding of fetal hemoglobin regulation in patients with sickle cell disease," says Guillaume Lettre, PhD, of the Broad Institute and Children's Hospital Boston, and co-first author on the paper. "But further validation experiments are needed before these findings can become useful in the clinic." "Eventually, understanding the factors giving rise to heterogeneity in HbF levels might allow us to take severely affected patients and make them more like those with more benign symptoms," adds Vijay Sankaran, co-first author on the paper with Lettre and an MD-PhD student in the laboratory of Stuart Orkin, MD. (Orkin is chair of pediatric oncology at DFCI and a Howard Hughes Medical Institute investigator at Children's.)
In sickle cell disease, a single genetic mutation results in the production of an abnormal type of hemoglobin, the main component of red blood cells. The abnormal hemoglobin molecules tend to form long chains, causing red blood cells to become stiff and sickle-shaped. The distorted cells have difficulty passing through blood vessels and can block the smaller vessels, resulting in severe pain and eventual organ damage as tissues are robbed of their blood supply. The sickle-shaped red blood cells also have a very short lifespan, causing patients to be chronically anemic.
Previous research had established that retaining high levels of another type of hemoglobin--HbF, found at high levels in the fetus--can ameliorate sickle cell disease symptoms. At birth, HbF comprises between 50 to 95 percent of a child's hemoglobin, gradually declining as the switch is made to adult hemoglobin production -- consistent with clinicians' observations that newborns diagnosed with sickle cell disease usually do not become symptomatic until they are about a year old. Population studies in Saudi Arabia and parts of India had identified groups of sickle cell patients with very high levels of HbF and relatively benign forms of the disease, and additional epidemiologic studies led by Orah Platt, MD, chief of laboratory medicine at Children's, showed that HbF is an ameliorating factor. "The more you have, the better off you are," says Sankaran.
Studying 1600 patients with sickle cell disease, the researchers found that previously identified DNA sequence variants in three chromosome locations (small regions on chromosome 2, 6, and 11) were associated with high or low HbF levels. When they added these five variants to a model previously designed by Platt to predict disease severity, which also factors in age, sex, degree of anemia and HbF levels, the model's predictive ability was enhanced.
The findings need to be validated in large, prospective clinical studies, but the researchers are hopeful about the possible future clinical implications of their work. "As we find gene variants that regulate HbF levels or predict severity, we might eventually want to genotype patients for these variants, to get more predictive information on their disease," Sankaran says.
Finally, once this study is validated, understanding how these variants actually affect HbF levels might someday lead to new drugs that do the same thing. "If we can gain better insight into what these variants are doing, we may eventually have better, more targeted therapies for sickle cell disease," adds Sankaran.
Lettre and Sankaran shared first authorship of the paper. Orkin and Joel Hirschhorn, MD, PhD, of Children's and the Broad Institute, were senior authors.This study was funded by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Howard Hughes Medical Institute.
Medicinal use of video games growing, may help pain
By DAVID TWIDDY The Associated Press http://www.kansascity.com/382/story/705991.html
This fall, researcher Carmen Russoniello will hand sickle cell anemia patients video game controllers and see whether playing the games helps them control stress and reduce pain caused by their disease.
Scientists, intrigued by video games' intrinsic ability to distract and focus the mind, have for decades looked for ways to use them to improve health and patient outcomes. Much of the work, however, has dwelt in obscurity as researchers struggled with small study sizes and lingering biases against what many considered a juvenile or even anti-social pastime. Even the video game industry has been unsure of what to make of the research, instead focusing primarily on the enjoyment aspect of game design.
But Russoniello, who has studied the physical and mental effects of recreation for 20 years, believes those perceptions are changing. For example, his sickle cell anemia study will be held in a clinical center operated by the highly selective and influential National Institutes of Health. In addition, insurance companies and a leading philanthropic organization have begun throwing big money behind video game research."Ten years ago, they would have laughed me out of that place," the East Carolina University researcher said. "But there's an acceptance of things. (Video games) aren't panaceas but they have their place and we need to find where that place is."
The Robert Wood Johnson Foundation announced in May that it would provide more than $2 million in grants for a dozen studies on the use of computer games for health. The projects range from using active video games, such as the Nintendo Wii, to encourage weight loss in children to seeing whether playing a driving-type video game improves cognitive and visual functions in senior citizens.This year's Games for Health conference, an annual get-together for medical scientists to review the latest in games-related research, drew more than 320 attendees, up from 120 when the meetings began four years ago, said co-founder Ben Sawyer.Among those attending this year's conference were representatives of such major health care organizations as Humana Inc., Cigna Corp. and Kaiser Permanente, which have all launched gaming projects in the past year.
Cigna, for instance, is distributing copies of the HopeLab-developed game ReMission to oncologists to give to their teenage cancer patients. The sci-fi shooter lets players blast cancer cells while learning how the disease progresses and what they can do to improve their health and well-being."Frankly, teens are a difficult group to reach," said Joe Mondy, assistant vice president of IT communications. "We think a video game approach reaches those kids where they are."
As happens in other areas of health, the research is actually trailing behind public behavior.A recent customer survey by Seattle-based PopCap Games Inc., maker of such casual games as Bejeweled, found that more than 20 percent of respondents identified themselves as having some level of physical or mental disability, and most of those said they used games as part of their therapy.One of those is Gail Nichols, 48, who said she has used video games to combat severe depression since the mid-1990s.The northeast Kansas resident, who said she suffers from post-traumatic stress disorder and other ailments, said she carries a Nintendo DS or Gameboy with her when she travels in case she begins feeling anxious or confused in public.
"If I get stressed out, my service dog is there with me. I'll pull (the game) out of her pack and between her being there with me and sitting there playing the game I won't be so nervous about people around me," Nichols said. "I would hope the medical community will add this to their bag of tricks."
Stem cell transplant for sickle cell disease subject of clinical trial
By Beth Miller http://mednews.wustl.edu/news/page/normal/12009.html
July 11, 2008 -- Children with sickle cell disease often face severe pain, organ damage, recurrent strokes and repeated, prolonged hospital stays. Although there are medical interventions that can lessen the symptoms, there is no cure.
In an effort to change that, researchers at Washington University School of Medicine in St. Louis are leading a nationwide, multicenter clinical trial to determine the effectiveness of transplanting blood stem cells from unrelated donors into children with severe sickle cell disease.
The Phase II clinical trial is led by Shalini Shenoy, M.D., associate professor of pediatrics at Washington University School of Medicine in St. Louis and medical director of the pediatric bone marrow transplant program at St. Louis Children's Hospital, and co-principal investigator Naynesh Kamani, M.D., of Children's National Medical Center in Washington, D.C. Children with severe sickle cell disease who qualify will receive a blood stem cell transplant from either bone marrow or umbilical cord blood to replace their own red blood cells. The trial seeks to enroll 45 patients ages 3-16 with symptoms of severe sickle cell disease, such as strokes, frequent pain or repeated episodes of acute chest syndrome, a painful obstruction of the blood vessels in the lungs.
To prepare to receive blood stem cells from a donor, patients must go through an intense treatment called conditioning to reduce production of their own blood cells and prevent their immune system from rejecting donor cells. For this trial, patients will receive reduced-intensity conditioning that could help them better tolerate the transplant with fewer toxic side effects of conditioning, such as infertility. As part of the trial, researchers will determine if the reduced-intensity conditioning treatment will allow the healthy donor blood stem cells to grow successfully in the patient.
Sickle cell disease is an inherited blood disorder affecting red blood cells, which contain hemoglobin, the substance that carries oxygen from the lungs to all parts of the body. In patients with this disease, red blood cells contain an abnormal type of hemoglobin that causes the normally round, flexible red blood cells to become stiff and sickle- or crescent-shaped. The sickle cells can't pass through tiny blood vessels, which can prevent blood from reaching some tissues and can result in tissue and organ damage, pain and stroke. In addition, sickle cells are short lived and lead to a shortage of red blood cells and anemia.
Sickle cell disease affects about 70,000 people in the United States and occurs in about 1 of every 500 African-American births and 1 of every 1,000 to 1,400 Hispanic-American births. Blood transfusions and bone marrow transplants have been shown to be effective treatments by replacing sickle cells with healthy red blood cells. However, blood transfusions have to be repeated regularly and can cause iron overload. Bone marrow transplants have a 10 percent mortality rate because of the possibility of infections, organ damage or graft-versus-host disease as donor cells work against the patient.
A healthy sibling who has the same tissue type as the patient is the best donor for a blood stem cell transplant, but few patients have such a suitable donor in their family. "So using unrelated donors who are close matches is the next best option if transplant is to be considered for this disease," Shenoy says. "Though, the probability of finding a good match is lower for minorities due to fewer minority donors registered in the National Marrow Donor Program, we think we can certainly find a good match for several of our patients," Shenoy says.
Physicians should only consider stem cell transplantation in children with severe cases of sickle cell disease and who have a closely matched donor, according to Shenoy."You only take a patient to transplant if the risk/benefit ratio is better by offering them the transplant," she says. "Right now, blood stem cell transplant is the only potential curative therapy for severe sickle cell disease."
In the preliminary trial, about 10 patients with sickle cell disease nationwide had successful blood stem cell transplants. The promising results generated interest in expanding the trial to a larger group of patients."For a successful outcome we need the red blood cells from the patient to be replaced by donor red cells without complications such as major graft-versus-host disease or organ damage," Shenoy says. "We think we have a good chance. If the donor red cells are rejected, we expect that the patient will recover his or her own red cells and remain at baseline with the disease."
The trial is supported by the Bone Marrow Transplant Clinical Trials Network of the National Heart, Lung, and Blood Institute, the National Marrow Donor Program, the Sickle Cell Disease Clinical Research Network and the Pediatric Blood and Marrow Transplant Consortium.
For more information about participating in the trial or about becoming a donor, contact Shenoy or Yvonne Barnes at (314) 454-6018 or visit the Bone Marrow Transplant Clinical Trials Network Web site at https://web.emmes.com/study/bmt
Sickle Cell Drug Underused by Physicians- Review of data on hydroxyurea shows it works, but long-term effects are unknown
Posted June 20, 2008 http://health.usnews.com/articles/health/healthday/2008/06/20/sickle-cell-drug-underused-by-physicians.html
FRIDAY, June 20 (HealthDay News) -- A drug that has shown some effectiveness in treating sickle cell anemia is not being used often enough by doctors who are uncertain about its proper use and possible long-term effects, according to a new report.
Researchers at Johns Hopkins University say their extensive review of studies on hydroxyurea clearly shows its helps people with sickle cell anemia, an inherited disorder that affects mostly people of African and Hispanic heritage. Their report, published in the June 17 Annals of Internal Medicine, concluded that hydroxyurea is a viable treatment option for now, but more quality research is needed.
About 70,000 people in the United States have sickle cell anemia, in which sickle-shaped blood cells periodically clump inside blood vessels, blocking circulation. This results in severe anemia, an increased risk of infections or strokes, and extreme episodes of pain that last for days.
The U.S. Department of Health and Human Services asked Johns Hopkins researchers to examine all previously published studies on hydroxyurea in an effort to increase awareness about the drug's potential.
"We know that many people with sickle cell disease aren't being offered this drug, which is the only one we have to treat this disease," Dr. Sophie Lanzkron, director of the Sickle Cell Center for Adults at Johns Hopkins, said in a prepared statement.
The team analyzed 246 quality articles on the drug and concluded it clearly works. The data suggests that once patients started taking hydroxyurea:
* Their episodes of painful sickle cell "crises" fell by 68 percent to 84 percent.
* Their hospital admissions declined by 18 percent to 32 percent.
* Their levels of fetal hemoglobin, a blood component that appears to eases sickle cell symptoms, increased by 4 percent to 20 percent.
The review also found hydroxyurea impairs sperm development in mice and may do the same in humans. The team, though, could not conclusively back theories that hydroxyurea increased or decreased the risk of leukemia or other tumors, leg ulcers and pregnancy complications from its review.
"It's clear from our literature review that hydroxyurea works, but we need to do much more work to understand how it works and the best ways to use it," Lanzkron says
Natural conception yields perfect match for transplant
Andrea W. Dilworth • Special to The Clarion-Ledger • July 15, 2008 http://www.clarionledger.com/apps/pbcs.dll/article?AID=/20080715/HEALTH/807150354/1242
Tammy and Anthony Witherspoon of McComb, both carriers of the sickle cell trait, were hesitant to bring another child into the world because of the 25 percent chance their offspring would be born with the genetic blood disease.
But when they learned son Anthony II's best chance for a cure was the umbilical cord blood of a healthy sibling, they decided to try in vitro fertilization, which they hoped would give them the opportunity to selectively implant an egg that was both free of sickle cell and a match.
"I had to cure my son," said Tammy, director of the Adolescent Offender's Program for the McComb School District.She mentioned it to Dr. Gail Megason, professor of pediatrics and director of the Division of Pediatric Hematology Oncology at the University of Mississippi Medical Center."Her words to me were, 'Bring me a healthy baby, a match.' So we did," Tammy said.
But it wasn't that simple. The in vitro fertilization, which cost the Witherspoons $12,000, was unsuccessful. The day of the scheduled implantation, Tammy and Anthony were told none of the 10 eggs doctors had retrieved from her had survived. Devastated but fertile from the medication she been taking to boost her fertility for implantation, Tammy and Anthony decided to "go home and do it the godly way. We put our faith in God and conceived the same day."
Nine months later, Amani (Swahili for faith in God) was born. Not only was he free of sickle cell, but he was a perfect match for Anthony II.Cord blood transplants are often the only option for patients with sickle cell, which primarily strikes African Americans, Megason said.
"We can find cord blood sometimes easier. It's harder finding a match for African-American patients because they are not on the national registry. It's just a cultural fear."The Witherspoons arranged to have Amani's umbilical cord blood collected by Viacord, a private cord blood bank. Months before her due date, Viacord sent the cord collection kit to the Witherspoons, who in turn took it with them to the hospital when Tammy was ready to deliver.
After Amani's delivery, doctors collected the cord blood, and a representative from Viacord picked it up for processing and storage, which takes six to eight weeks.Private banks usually charge $1,500 to $2,000 to collect, process and store units, but because of the Witherspoons' pre-existing need, their fees were waived.Anthony II wasn't able to undergo the transplant right away, though. Doctors needed to extract bone marrow from Amani to serve as a boost during the cord blood transplant, Tammy Witherspoon said. Amani had to be at least a 1-year-old for the procedure. It was a long wait, but well worth it.
Three years later, at 13, there are no signs of sickle cell anemia in Anthony II's blood, Tammy said."He is the healthiest one in the house. Every mother's dream is to have a healthy kid."
Megason does not recommend that all expectant parents make plans to bank their newborn's cord blood for private use.The Witherspoons, however, are a special case."For patients who have a child with sickle cell, leukemia or other genetic diseases that can be cured by transplantation, if you already have a child with such a disease, you would want to collect cord blood," Megason said.
National guidance issued on treating sickle cell in England
* Published: 09 July 2008 12:25 Author: Alice Coubrough http://www.nursingtimes.net/clinicalnews/2008/07/national_guidance_issued_on_treating_sickle_cell.html
The standards, published by the Sickle Cell Society, http://www.sicklecellsociety.org include guidelines for nurses in primary care as well as specialist networks for hospitals and clinics. The guidance deals with topics such as the management of chronic and acute conditions, blood transfusions, and screening.
Dr Allison Streetly, programme director for the NHS Sickle Cell and Thalassaemia Screening Programme, said: 'The introduction of these much needed national guidelines on caring for adults with the disease is greatly welcome.'Together with the care standards for thalassaemia they lay the foundation for a care framework where patient needs are properly understood both close to where people live and in specialist centres,' she added.
With sickle cell being one of the most commonly inherited genetic diseases in England, the charity said its next challenge would be to improve understanding of sickle cell and thalassaemia among both the public and healthcare professionals. The standards coincide with Sickle Cell Awareness Month, which has activities running across the country throughout July to improve awareness and management of the disease.
Dr Lorna Bennett, Chairperson, Sickle Cell Society said: ' The reality is that provision of care for adults with sickle cell disease can vary significantly between individual professionals as well as health care provision organisations. These standards are the tool needed to address the inequalities in provision and access to good quality care.' The full text PDF guide book can be downloaded athttp://www.sicklecellsociety.org/CareBook.pdf
New Center for Sickle Cell Disease Research, treatment, care to be brought together
By Katerina Pesheva Johns Hopkins Medicine http://www.jhu.edu/~gazette/2008/07jul08/07sickle.html
Johns Hopkins Children's Center has received a nearly $5 million grant from the National Heart, Lung and Blood Institute to establish a basic and translational research center for sickle cell disease that will consolidate research, treatment and care of adult and pediatric patients under one roof and speed up the translation of scientific discovery from bench to bedside. In addition, the center will offer counseling and education services to patients and their families.
Sickle cell disease is an inherited blood disorder marked by a mutation in the hemoglobin genes. The defect causes oxygen-starved, abnormal crescent-shaped red blood cells that give the disorder its name. The sickle-shaped cells get stuck in blood vessels, leading to excruciatingly painful strokes and organ damage. Sickle cell anemia affects nearly 72,000 Americans, primarily African-Americans.
"This center will be a marriage of all aspects of science and treatment, from basic science and clinical research to patient care and public health research, all part of the quest to treat and ultimately cure sickle cell disease," said lead investigator James F. Casella, Rainey Professor and chief of Pediatric Hematology at Johns Hopkins.
By drawing on the expertise of researchers from diverse areas, the center's faculty and staff expect to advance promising therapies more rapidly. For example, a basic-science project led by Allen Everett, a pediatric cardiologist, will use the science of proteomics, the study of proteins, to look for biomarkers involved in silent strokes, which are a leading cause of neurologic complications in sickle cell patients. Discoveries in this area will ultimately lead to better understanding, earlier diagnosis, treatment and prevention of neurovascular problems in sickle cell patients.
On the public health end of the spectrum, researchers from the Johns Hopkins Bloomberg School of Public Health, led by Cynthia Minkovitz, will examine how local public health services affect disease course and survival, and then pinpoint public health measures that will help eliminate state-to- state disparities in patient outcomes.
The translational arm of the center, led by urologist Arthur Burnett, will help take lab discoveries to the patient's bedside. For example, scientists will study the role of nitric oxide in sickle cell priapism, long-lasting painful erections that are a common complication of the disease. Researchers will then examine whether certain medications that affect nitric oxide levels might reduce and prevent this dreaded complication, which often requires treatment at the emergency room or hospitalization.
The center will also support a faculty scholar in sickle cell disease and a summer program in sickle cell disease research for high school students.Other partners on the grant include the University of Alabama, which, like Johns Hopkins, has a long history of sickle cell disease research and care. In February, The Johns Hopkins Hospital opened an urgent care center that specializes in treating sickle cell patients experiencing acute pain. In 2000, Hopkins opened an adult sickle cell disease center that focuses on chronic care.
New hope for bone marrow patients - An advance in stem cell research could one day give hope to patients in need of bone marrow transplants or blood transfusions, scientists have said.
Edinburgh experts used blood stem cells from mice to mimic how humans produce the stem cells and found they were able to multiply them by 150 times. They hope their findings will lead to efficient production of blood stem cells in the laboratory. They could then multiply in the body to renew a patient's blood supply.
The body generates billions of blood cells every day, which are produced by blood stem cells in the bone marrow tissue. These include red blood cells, which deliver oxygen to different organs, and white blood cells, such as lymphocytes and macrophages, which play an important role in the body's immune system.
The University of Wisconsin Pain & Policy Studies Group (PPSG) Releases new Documents for Pain Management
· Achieving Balance in Federal and State Pain Policy: A Guide to Evaluation (Fifth edition), http://www.painpolicy.wisc.edu/Achieving_Balance/EG2008.pdf
· Achieving Balance in State Pain Policy: A Progress Report Card (Fourth edition)http://www.painpolicy.wisc.edu/Achieving_Balance/PRC2008.pdf
These resources are part of the PPSG’s continuing pain and public policy research program.
The Evaluation Guide is the fifth in a series of evaluations of federal and state pain policies. The Progress Report Card quantifies state pain policies, and tracks progress to promote pain management and reduce policy barriers by comparing 2008 state policy grades with those from 2000, 2003, 2006, and 2007. These two reports are important tools that can be used by government and non-government organizations, as well as policy-makers, healthcare professionals, and advocates to understand the policies in their state that reinforce the right to pain management, or that can hinder patient access to effective treatment.
Visit the PPSG website at www.painpolicy.wisc.edu to view or download these reports, as well as a national press release, Frequently Asked Questions, and a summary of grade changes
Texas Program targets sickle cell disease
by JAN JARVIS email@example.com http://www.star-telegram.com/health/story/746443.html
Desmond Woods tried to tough it out the morning he woke up with pain pulsating through his body. But by that night, he could no longer stand what is a common and debilitating effect of sickle cell disease.
"It’s like being stabbed over and over," said Woods, 27, of Fort Worth. "All my joints were just aching, and I was in tears crying because of the pain."
Like other adults with the disease, Woods has been in and out of hospitals searching for relief. Getting care can be difficult. Some medical workers "don’t even know what sickle cell is all about," he said. To address the concern, Harris Methodist Southwest Hospital is spearheading a program to close the gap in care for adults with sickle cell disease. Tarrant County Public Health, the Sickle Cell Disease Association and several area hospitals are also working on the project.
* Reducing quick-fix emergency-room visits by helping patients better manage pain.
* Putting protocols in place so patients get aggressive care as soon as they arrive in the emergency room.
* Encouraging all Tarrant County hospitals to adopt the protocols.
* Developing a day clinic and finding physicians to manage the patients.
In Texas, infants are screened for the disease and children receive care through pediatric specialists, said Mary Robinson, vice president of patient care services at Harris Methodist Southwest. But access to care changes when patients turn 18. Tarrant County has several comprehensive pediatric programs for children with sickle cell disease, said Linda Humphries, clinical nurse specialist at Harris Methodist Southwest. But once those children grow up, they tend to fall through the cracks.
"They’re not finding consistent care, so they start using the ER as their source of treatment for sickle cell," she said. Along with acute pain in their joints and backs, patients often are dehydrated when they arrive at the hospital. The kidneys, spleen, liver and other organs can be damaged. Pneumonia, urinary tract infections, gallstones and joint destruction can lead to lengthy hospitalizations. "This year I’ve been hospitalized at least four or five times," Woods said.
By teaching adults to identify triggers — including stress, infection and weather changes — the hope is they will be better able to manage their disease and avoid hospitalizations, Robinson said. When patients do end up at the hospital, knowing how to treat them aggressively will also make a difference.
Decades ago, many sickle cell patients did not reach adulthood; today, many live to their 40s. "They are surviving longer and they are still leading productive lives," Humphries said.
New Pain Advocacy Resource at www.inthefaceofpain.com
Sickle Cell Disease is featured in In the Face of Pain®, a new online advocacy toolkit designed to help healthcare professionals and patient advocates achieve greater awareness and understanding of undertreated pain as a serious national health problem.
In the Face of Pain is an interactive toolkit that enables advocates to create individualized action plans, educational materials, and presentations tailored to a specific pain-related topic. The toolkit – which can be accessed at www.inthefaceofpain.com – serves as a one-stop location for pain-related statistics and provides guidance on implementing advocacy outreach through various channels, including:
* Community groups
* Professional organizations
“We hope this toolkit will be a valuable resource for patients, caregivers and healthcare professionals as they work to alleviate unnecessary suffering and improve pain care practice and policy through education and advocacy,” said Pamela Bennett, RN, BSN, Executive Director, Healthcare Alliance Development at Purdue Pharma L.P., which developed the In the Face of Pain Online Advocacy Toolkit.
Caution a must for athletes with sickle-cell trait
Athletes who possess the sickle-cell trait can play competitive sports but should be monitored by trainers if they participate in intense workouts, according to guidelines published by both the NCAA and the National Athletic Trainers Association.
The Orange County medical examiner found that symptoms associated with sickle-cell trait caused UCF football player Ereck Plancher to collapse and die after an off-season workout on March 18.
The 2008-09 NCAA Sports Medicine Handbook urges athletic trainers to exercise caution when supervising athletes diagnosed with the blood disorder, as UCF officials confirm Plancher was in 2007. Sickle-cell trait can hamper the ability of cells to carry oxygen when triggered by physical stress, a condition called sickling.
"The harder and faster athletes go, the earlier and greater the sickling," the handbook states. "Sickling can begin in only two to three minutes of sprinting, or in any other all-out exertion of sustained effort, thus quickly increasing the risk of collapse. Athletes with sickle-cell trait cannot be conditioned out of the trait and coaches pushing these athletes beyond their normal physiological response to stop and recover place these athletes at an increased risk of collapse."
Even the most fit athletes with the trait can experience a collapse, the NCAA warns.
Plancher is the 10th athlete between the ages of 12 and 19 to die after intense physical exertion from complications related to sickle-cell trait, according to NATA, which in 2007 released a "consensus statement" in which it warned trainers across the country that athletes with the sickle-cell trait were at risk during "intense exertion." Scott Anderson, head athletic trainer at the University of Oklahoma and co-chair on the task force that produced the NATA statement, said there was a lack of knowledge about the trait within the athletic population so the goal was to educate across the board. NATA suggests screening athletes for the trait and says 64 percent of Division I-A schools who responded to a survey do test for it. UCF is among those schools.
Also see http://www.orlandosentinel.com/sports/orl-ucfbox1908jul19,0,1811971.story
Ereck Plancher's death has been linked to a single genetic flaw that millions of Americans share. It's called sickle-cell trait, and many of those who have it never know they do. That's because it rarely causes symptoms and is not even considered a medical condition or disease.
Yet an expert said Friday that some people with sickle-cell trait are vulnerable to sudden death under severe stress -- such as heat, physical exertion and dehydration. The reasons are not clear, however, and doctors say most with the trait have nothing to fear.
"It only very rarely leads to problems -- it's almost always benign," said Dr. James R. Eckman, an expert in sickle-cell trait and a professor of hematology and oncology at Emory University in Atlanta. "But under the extremes of human endurance, there can be problems. People need to understand this is a very unusual situation." There is one important caveat: Those with the trait can pass the errant gene on to their children. And if both parents have it, they have a one-in-four chance of having a child with full-scale sickle-cell disease. That's why African Americans and people in other risk groups are encouraged to find out whether they carry the gene. Beyond that, Eckman said, those with the trait do not have medical concerns in most circumstances.
One exception may be under extreme physical duress. Eckman said research suggests that exertion, dehydration and heat may trigger the distortion of red blood cells that can impede flow and starve organs of needed oxygen. But he said that risk is very small and can be reduced even further if athletes take basic precautions by drinking plenty of fluids and not overdoing it. And that's good advice for everyone -- even those without sickle-cell trait.
"Again, this is very rare," Eckman said. "In most cases, a person with sickle-cell trait does not have any symptoms, and they should be able to participate in all sports."
Sickle: A sickle crisis? (2008)
A Health outcomes study group in England, NCEPOD, was pleased to undertake a review of current haemoglobinopathy mortality, to obtain broad baseline data and make recommendations to alter practice. In this way, we hope to contribute to improving the quality of life of patients – whose numbers and attendances at health care centres are inevitably going to increase. A Full text PDF of the report and summary slides are available at http://www.ncepod.org.uk/2008sc.htm
New Grant RFP
Title: Meetings, Conferences, and Networks for Research Partnerships to Improve Functional Outcomes (R13)
Details at http://grants.nih.gov/grants/guide/pa-files/PAR-08-207.html
In 2004, the NIH Rehabilitation Coordinating Committee developed a program announcement (PAR-04-077) entitled “Research Partnerships to Improve Functional Outcomes” in order to stimulate multi-disciplinary research into the difficult problems of chronic disease and rehabilitation The goal of this initiative was to encourage applicants with clinical expertise in rehabilitation or management of chronic disease to partner with scientists outside their fields to develop innovative approaches to problems. Although the announcement did generate a number of responsive applications across a wide scope of research problems, most applicants had significant difficulties in articulating how the expertise of their teams would actually go about addressing their chosen problems. In other words, applicants were successful in recruiting appropriate multi-disciplinary teams, but not in working with them to forge coherent research plans.
The present FOA attempts to address this problem by supporting meetings and workshops to bring together investigative teams to facilitate the process of developing appropriate research plans. We seek to help investigators who have the same interests in solving particular problems of rehabilitation and chronic disease, including mental disorders, and who have complementary research or clinical expertise and/or resources team up and form partnerships to coordinate, exchange, and disseminate information or to explore or clarify a defined subject, problem or area of knowledge. Proposed workshops and conferences should especially address issues in research methodology, including (but not limited to) selection of appropriate subjects, sample size, subject recruitment, measurement, trial design, and analytic strategies. It is anticipated that these workshops and conferences will help investigators become successful in submitting competitive applications for investigator-initiated research projects in the future.
Articles in the Medical Literature
Adams-Graves P, Lamar K, Johnson C, Corley P. Development and validation of SIMS: an instrument for measuring quality of life
of adults with sickle cell disease. Am J Hematol. 2008 Jul;83(7):558-62.http://www3.interscience.wiley.com/journal/117873602/abstract?CRETRY=1&SRETRY=0
Streetly A, Clarke M, Downing M, Farrar L, Foo Y, Hall K, Kemp H, Newbold J, Walsh P, Yates J, Henthorn J. Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005. J Med Screen. 2008;15(1):9-13.http://www.ncbi.nlm.nih.gov/pubmed/18416948?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Zempsky WT, Loiselle KA, McKay K, Blake GL, Hagstrom JN, Schechter NL, Kain ZN. Retrospective evaluation of pain assessment and treatment for acute vasoocclusive episodes in children with sickle cell disease. Pediatr Blood Cancer. 2008 Aug;51(2):265-8.http://www.ncbi.nlm.nih.gov/pubmed/18386784?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Taori KB, Chaudhary RS, Attarde V, Dhakate S, Sheorain V, Nimbalkar P, Wasnik PN. Renal Doppler indices in sickle cell disease: early radiologic predictors of renovascular changes. AJR Am J Roentgenol. 2008 Jul;191(1):239-42.http://www.ncbi.nlm.nih.gov/pubmed/18562752?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Klings ES, Anton Bland D, Rosenman D, Princeton S, Odhiambo A, Li G, Bernard SA, Steinberg MH, Farber HW. Pulmonary arterial hypertension and left-sided heart disease in sickle celldisease: clinical characteristics and association with soluble adhesion molecule expression.cAm J Hematol. 2008 Jul;83(7):547-53. http://www.ncbi.nlm.nih.gov/pubmed/18383329?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Field JJ, Glassberg J, Gilmore A, Howard J, Patankar S, Yan Y, Davies SC, Debaun MR, Strunk RC. Longitudinal analysis of pulmonary function in adults with sickle cell disease. Am J Hematol. 2008 Jul;83(7):574-6.http://www.ncbi.nlm.nih.gov/pubmed/18383325?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H, Witkop C, Bass EB, Segal JB. Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med. 2008 Jun 17;148(12):939-55. Epub 2008 May 5. Full Texthttp://www.annals.org/cgi/content/full/148/12/939
Brawley OW, Cornelius LJ, Edwards LR, Gamble VN, Green BL, Inturrisi C, James AH, Laraque D, Mendez M, Montoya CJ, Pollock BH, Robinson L, Scholnik AP, Schori M. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008 Jun 17;148(12):932-8. http://www.annals.org/cgi/content/full/148/12/932
Harban FM, Connor P, Crook R, Bingham R. Cardiopulmonary bypass for surgical correction of congenital heart disease in children with sickle cell disease: a case series. Anaesthesia. 2008 Jun;63(6):648-51. Epub 2008 Feb 29.http://www.ncbi.nlm.nih.gov/pubmed/18312603?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Alvarez O, Lopez-Mitnik G, Zilleruelo G. Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer. 2008 Jun;50(6):1236-9. http://www.ncbi.nlm.nih.gov/pubmed/18293385?ordinalpos=17&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Singh SA, Koumbourlis AC, Aygun B. Resolution of chronic hypoxemia in pediatric sickle cell patients after treatment with hydroxyurea. Pediatr Blood Cancer. 2008 Jun;50(6):1258-60. http://www.ncbi.nlm.nih.gov/pubmed/18293380?ordinalpos=18&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Dyson, SM; Abuateya, H; Atkin, K; Culley, LA; Dyson, SE; and Rowley, DT (2008) Local authorities and the education
of young people with sickle cell disorders (SCD) in England International Studies in Sociology of Education 18 (1) 47-60. [
ISSN 0962-1214] doi:10.1080/09620210802196168 http://dx.doi.org/10.1080/09620210802196168
Abuateya, H; Atkin, K; Culley, LA; Dyson, SE and Dyson, SM (2008) Young People with Sickle Cell Disorder and Education:
A Knowledge Review Diversity in Health and Social Care 5 (2): 123-135. [ISSN 1743-1913]
Ask the Experts
Are there some famous people with sickle cell disease
All patients with sickle cell disease are heroes, but here are some who are in the public eye
* Miles Davis, jazz musician.
* Paul Williams, singer (The Temptations)
* Georgeanna Tillman, singer (The Marvelettes)
* Tionne "T-Boz" Watkins, singer (TLC)
* Prodigy, rapper (Mobb Deep).
* Hertz Nazaire - Artist
Let us know if there are others.
For more frequently asked questions please see: http://www.scinfo.org/faq.htm
Featured Web Links
A recommitment to sickle cell disease research - The NIH agenda full text athttp://bloodjournal.hematologylibrary.org/cgi/content/full/111/10/4852
Patient Advocate Foundation at http://www.patientadvocate.org/
A New and Improved HealthFinder.gov web site at http://beta.healthfinder.gov
New Pain Advocacy Resource at www.inthefaceofpain.com
Conferences and Activities of Interest to the Sickle Cell Community
www.sicklecelldisease.org Call for abstractshttp://www.sicklecelldisease.org/docs/2008%20Call%20for%20Abstracts%2004.09.08.doc
September 18, 2008 Chicago - Management of Sickle Cell Disease Conference 2008 “ Multidisciplinary Approach” Hilton Oak Lawn- Astoria Ballroom 9333 S Cicero Ave. Oak Lawn IL. 60453 Contact: Jo Ann Allen 312-345-1100.
Friday September 5, 2008 Annual Sickle Cell Golf Classic Ramblewood Golf & Country Club, 200 Country Club Parkway, Mt. Laurel, N.J. Tee Time: 11:00 am
Saturday September 20, 2008 Annual Sickle Cell Seminar Philadelphia International House 3701 Chestnut Street 10:00 am- 4:00 pm.
Saturday September 27, 2008 11th Annual Walter E. Brandon Sickle Walkathon & " Lighten the Load " CD Launch Party Philadelphia Carousel House
Belmont Avenue & North Concourse Drive 8:00 am- 2:00 pm
Saturday September 27, 2008 " Dancing with the Philadelphia Stars " 7:00 - 12:00 pm
For specific information about each event or sponsorship opportunities contact: Sickle Cell Disease Association of America, Philadelphia/ Delaware Valley Chapter215-471-8686 or visit our website at www.sicklecelldisorder.com
The Sickle Cell Thalassemia Patients Network , NY, The Sickle Cell Disease Association of America, of Southern, CT The Sickle Cell Disease Association of America, Philadelphia/Delaware Valley The Donna T. Darrien Memorial Foundation For Sickle Cell Inc. Newark, NJ
Celebrities Isaac Hayes and WBLS DJ Dr. Bob Lee For more information E-mail: firstname.lastname@example.org
Special Guest Speaker: Dr Michael R DeBaun Venue: Governor’s Hall, St Thomas Hospital , London . United Kingdom
· New Diagnosis Frontiers, including Mass spectrometry (MSMS) · Cutting Edge Research and Iron Chelation · Stem Cell Transplantation, Pre-implantation Genetic Diagnosis. · Asthma, Obstructive Sleep, Avascular Necrosis , Endocrine · NECPOD: Confidential Enquiry into Sickle Cell Disease
Contact: Mary.Abiri@gstt.nhs.uk, 44(0)2071887774, or Helen.Appleby@gstt.nhs.uk
Web Site: www.mysite.verizon.net/bizst88q/ Email: email@example.com phone 727-896-2355
Can Flying High Make you Sick?
By Kate McHugh, Ivanhoe Health Correspondent http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=16579
ORLANDO (Ivanhoe Newswire) -- Could that turning feeling in your stomach during an airplane flight be something other than nerves?
A new study in The New England Journal of Medicine tested the effects of exposure to high altitudes to see if acute mountain sickness -- a sensation felt by visitors to mountainous areas -- could be experienced by airplane passengers as well.
Researchers found oxygen in the blood decreased by 4.4 percent at 7,000 to 8,000 feet -- the altitude at which acute mountain sickness is experienced. However, only 7.4 percent of the participants reported complaints of mountain sickness. The symptoms were first felt after 3 to 9 hours of exposure to high altitudes.
So why are symptoms different when the altitudes are the same? Michael, Zimring, M.D., and director of the Center for Wilderness and Travel Medicine at the Mercy Medical Center in Baltimore, Maryland, has a theory -- and it's all about exertion.
"When you go up in a plane to 8,000 feet, you're sitting, you're doing nothing, you're not exerting energy, you don't need as much oxygen, so therefore you're not going to have a problem with a couple hour flight with altitude sickness," Dr. Zimring told Ivanhoe. "Whereas when you go up skiing, if you're young and active and healthy, you're going to be exerting yourself right away. That's where you get acute mountain sickness."
Dr. Zimring recommends all travelers drink lots of water to stay hydrated. He also says unhealthy patients with lung cancer, heart disease or sickle cell disease may experience altitude sickness in airplanes as well.
Sickle cell testing for athletes increases MU athletes do not have to be tested, but they can opt for test.
By ALEX LANGE http://www.columbiamissourian.com/stories/2007/07/13/sickle-cell-testing-athletes-increases/
It’s been two years since MU football player Aaron O’Neal died during a voluntary practice at Faurot Field. O’Neal’s death was initially attributed to lymphocytic meningitis by then-Boone County Medical Examiner Valerie Rao. A University Hospital neuropathologist who examined O’Neal’s brain later said sickle cell trait could have played a role. As a result, the sickle cell trait might factor into the wrongful death lawsuit brought by O’Neal’s parents against 14 current and former members of the athletic department. In the two years since O’Neal’s death, the number of MU student athletes who have asked to be tested for sickle trait has increased tenfold — from five to almost 50. But MU’s athletic department has not instituted mandatory testing for the trait, nor does the NCAA require it. “Testing is still not mandatory, and I don’t think that it is ever going to be mandatory,” said Rex Sharp, MU’s director of sports medicine. “I just don’t see that happening right now.” Sickle cell trait is a condition that can cause red blood cells to logjam in veins and arteries and block the vital flow of oxygen to muscle tissue during strenuous exercise.
Athletic trainers step up efforts to combat sickle cell trait
The National Athletic Trainers Assn., with more than 6,000 in attendance in Anaheim this week, on Wednesday took a first step toward making the athletic field safer for black athletes, as well as others who carry the potentially lethal sickle cell trait.
Having spearheaded a task force that included more than 20 organizations, the NATA recommended that colleges and high schools show greater awareness of the typically benign condition, which poses a grave risk during intense exertion of physical activity.
"You can take a body of athletic trainers, a body of team physicians, a body of family practice physicians, a body of coaches and athletes, if you ask them what are the non-traumatic causes of deaths for athletes, No. 1 they would say cardiac, No. 2 they would say heat stroke, but after that you'd probably get a lot of head scratching," said Scott Anderson, head athletic trainer at Oklahoma and co-chair of the task force. "Sickle cell trait is the third-leading cause of non-traumatic death at the secondary and collegiate level."
The inherited blood disorder ranks just ahead of asthma, the No. 4 killer.
"We have a lot of kids with asthma," said Lou Randall, who coached Riverside North to the Southern Section's Eastern Division football title. His program is comprised of about 60% black athletes and, statistically, would have about seven or eight players with the trait. "As far as I see, there's nothing in the medical history that shows" sickle cell trait. "I could be wrong. I look for what they're allergic to and if they've had any major injuries."
Randall isn't the only one in the dark.
Anderson cited the similarity in deaths of the first college football player to die of sickle cell trait, Colorado sophomore Polie Portier in 1974, and the most recent, Rice freshman defensive back Dale Lloyd in 2006.
"Thirty-two years later, the athlete, the coaches, the athletic trainer didn't know he had it. Nothing's changed," Anderson said. "There was no association with exertion rate and sickle cell trait. There's a lack of awareness of the syndrome or the risk."
Sickle cell trait is the inheritance of one gene for sickle hemoglobin and one for normal hemoglobin. Under extensive exertion, the sickle hemoglobin can change the shape of red blood cells to that of a quarter moon, or the shape of a farmer's sickle.
Although newborn children are screened for the trait, by the time they enter high school they are often unaware of their condition, which is why the NATA recommended secondary institutions and universities consider testing an athlete, Anderson said, essentially "for the cost of a pizza" from certain laboratories.
Over the past seven years, nine athletes — including a 14-year-old female basketball player and two 12-year-olds training for football — have died when their red blood cells began "sickling." The sickle-shaped cells create a logjam in the blood vessels which can lead to collapse from the rapid breakdown of muscles starved for blood.
Deadly sickling can begin in two to three minutes of any all-out exertion, such as running sprints or stadium steps, and poses a grave risk to athletes if they aren't allowed a longer recovery period between repetitions. Lloyd, the Rice football player, died after running 16 sprints of 100 yards.
One of the critical points of the consensus statement was that having the trait should not prevent an athlete from participation, however training should build up slowly with paced progressions. Athletes should ideally work at their own pace, engage in year-round strength and conditioning programs that meet sport-specific demands, and cease activity with the onset of symptoms such as muscle cramping, pain, swelling, weakness, tenderness, the inability to catch one's breath or fatigue.
About 8% of the general African-American population in the U.S. has the trait, and a study showed that 7% of African-American players in the NFL have it. Among those are Devard Darling, wide receiver for the Baltimore Ravens, whose twin brother, Devaughn, a freshman linebacker at Florida State, died of complications from sickle cell trait in 2001. Devard, one of the featured speakers Wednesday, also carries the trait.
"A lot of people who are in position to help, coaches at the secondary level, they aren't aware of the trait, aren't up to date with the protocols, the trauma," Darling said. "You can't bury your head in the sand and think nothing is happening. Kids are dying, and it's time for people to do something about it. Athletic trainers, they have to know. More important, the athletes have to know their bodies and have to know they carry the trait.
"It needs to be on every high school application."
More information is available at http://www.nata.org
Network Model Predicts Risk of Death in Sickle Cell (Boston) – Researchers from Boston University School of Medicine (BUSM) and Boston University School of Public Health (BUSPH) have developed a method to estimate sickle cell disease severity and predict the risk of death in people with this disease. The study appears online in the June issue of the journal Blood http://www.bu.edu/phpbin/news/releases/display.php?id=1367
Recovery Difficult, but New Treatment Gives Teen New Hope
Experimental bone marrow transplant rids girl's body of sickle cell
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