BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD.Chronic kidney disease is defined as abnormalities of kidney structure or function, present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD.Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, and increases in prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. OBJECTIVES: To assess the effectiveness of any intervention in preventing or reducing kidney complications or chronic kidney disease in people with SCD (including red blood cell transfusions, hydroxyurea and angiotensin-converting enzyme inhibitor (ACEI)), either alone or in combination with each other. AUTHORS' CONCLUSIONS: In young children aged 9 months to 18 months, we are very uncertain if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration, but it may improve young children's ability to concentrate urine and may make little or no difference on the incidence of acute chest syndrome, painful crises and hospitalisations. We are very uncertain if giving ACEI to adults with normal blood pressure and microalbuminuria has any effect on preventing or reducing kidney complications.This review identified no trials that looked at red cell transfusions nor any combinations of interventions to prevent or reduce kidney complications. Due to lack of evidence this review cannot comment on the management of either children aged over 18 months or adults with any known genotype of SCD.We have identified a lack of adequately-designed and powered studies, and no ongoing trials which address this critical question. Trials of hydroxyurea, ACEI or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction kidney complications in people with SCD. Abstract source Full text

BACKGROUND: Persons with sickle cell disease (SCD) are particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review first published in 2002, and previously updated, most recently in 2014. OBJECTIVES: To assess the effects of antibiotic prophylaxis against pneumococcus in children with SCD in relation to:1. incidence of infection;2. mortality;3. drug-related adverse events (as reported in the included studies) to the individual and the community;4. the impact of discontinuing at various ages on incidence of infection and mortality. MAIN RESULTS: Five trials were identified by the searches, of which three trials (880 children randomised) met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with SCD (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-quality evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-quality evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five. Overall, the quality of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). Abstract source Full text

Acute painful episodes are the most common reason for emergency department visits among patients with sickle cell disease (SCD). Early and aggressive pain management is a priority. Emergency providers (EPs) must also diagnose other emergent diagnoses in patients with SCD and differentiate them from vaso-occlusive crisis. EPs should be aware of cognitive biases that may misdirect the diagnostic process. Administration of intravenous fluids should be used judiciously. Blood transfusion may be considered. Coordination of care with hematology is an important part of the effective emergency department and long-term management of patients with SCD. Abstract source Full text

We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels. Hydroxyurea was associated with a significant reduction in the incidence of acute chest syndrome (-29.3%, p<0.001), vaso-occlusive crisis (-34.1%, p<0.001), hospitalization (-53.2%, p<0.001), and bone necrosis (-6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (βS/βS, βS/β0 or βS/β+) and duration of treatment (< or >=10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681). Abstract source Full text

Matthew Karafin, MD, MS is the associate medical director, Medical Sciences Institute, BloodCenter of Wisconsin. He is also an assistant professor of pathology at Medical College of Wisconsin. Dr. Karafin’s major responsibilities include Transfusion service work and instruction of medical students, residents, and fellows in general pathology and Transfusion Medicine. He oversees the Blood Bank and Therapeutic apheresis services for Froedtert Hospital/Medical College of Wisconsin and also directly supervises pathology residents on their coagulation rotations. Research Interests: - Transfusion Therapy in Sickle Cell Disease - Human Alloimmunization - Red Cell Genotyping - Immunohematology - Transfusion-Associated Hemolysis Online profile

Dr. King is a pediatric hematologist and oncologist. She focuses her research on educational outcomes of two populations of children with chronic diseases: children with sickle cell disease (SCD) and children with brain tumors. She is investigating variables related to academic achievement and self-sufficiency, including socioeconomic status and family dynamics. Dr. King’s research focuses on factors that impact a child’s opportunity to learn. From a biological standpoint, she studies how chronic diseases such as sickle cell disease or brain tumors alter cognition. In addition, Dr. King studies the environment’s influence on children’s development and participation. The goal of this work is to determine targets for intervention that will have the greatest impact on development and education. She is also working on a public health project to educate African Americans about their sickle trait status and is partnering with a local federally-qualified health center and local churches to complete education, trait testing and genetic counseling. Online profile

Cindy Neunert, MD is a practicing pediatric hematologist-oncologist in New York, NY. Dr. Neunert graduated from Eastern Virginia Medical School in 2001 and has been in practice for 16 years. Dr. Neunert also specializes in Pediatrics. Interests/Specialties:- Pediatric Hematology-Oncology- Pediatrics Conditions:- Sickle Cell Anemia- Pediatric Hematology-Oncology- Anemia, Iron Deficiency- Pediatric Leukemia- Bleeding/Clotting Disorder- Pediatric Hemophilia- Pediatric Vascular Anomalies Online profile

If you suffer from sickle cell anemia and your symptoms are so severe you are unable to work, you may be eligible to receive monthly Social Security disability benefits. The Social Security Administration (SSA) oversees Social Security Disability Insurance (SSDI), which is a program that pays monthly benefits to those who have become unable to work because of medical conditions if specific requirements are met and you are deemed completely disabled. The most commonly diagnosed blood disorder, sickle cell anemia impacts one out of every 500 African Americans and one out of every 1,000 to 1,400 Hispanic Americans throughout the country. In sickle cell anemia, your red blood cells are misshapen because they contain abnormal kinds of hemoglobin. These defectively shaped cells can block off your smaller blood vessels, and in turn, cause strokes or tissue damage. Other problems, such as severe anemia, gallstones, jaundice, leg and arm pain, or damage to the liver, spleen, or kidneys may also result. The levels of severity can vary. Abstract source

A. What hematological disorders do we evaluate under these listings? - We evaluate non-malignant (non-cancerous) hematological disorders, such as hemolytic anemias (107.05), disorders of thrombosis and hemostasis (107.08), and disorders of bone marrow failure (107.10). These disorders disrupt the normal development and function of white blood cells, red blood cells, platelets, and clotting-factor proteins (factors). - We evaluate malignant (cancerous) hematological disorders, such as lymphoma, leukemia, and multiple myeloma, under the appropriate listings in 13.00, except for two lymphomas associated with human immunodeficiency virus (HIV) infection. We evaluate primary central nervous system lymphoma associated with HIV infection under 114.11B, and primary effusion lymphoma associated with HIV infection under 114.11C. B. What evidence do we need to document that you have a hematological disorder? We need the following evidence to document that you have a hematological disorder: - A laboratory report of a definitive test that establishes a hematological disorder, signed by a physician; or - A laboratory report of a definitive test that establishes a hematological disorder that is not signed by a physician and a report from a physician that states you have the disorder. Abstract source

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg/day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events, clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N=104) or placebo (N=103). Malaria incidence did not differ between children on hydroxyurea [0.05 episodes/child/year, 95% CI (0.02, 0.13)] versus placebo [0.07 episodes/child/year (0.03, 0.16)]; the hydroxyurea/placebo malaria incidence rate ratio was 0.7 [(0.2, 2.7), p=0.61]. Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%, p=0.001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious adverse events, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (two hydroxyurea, one placebo, none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or adverse events. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. Abstract source Full text