Pharmacy & Therapeutics - April 2008 - (Page 239) CONTINUING EDUCATION CREDIT Table 1 Prophylaxis of Complications from Sickle Cell Disease Complication Streptococcus pneumoniae sepsis Prophylactic Therapy Newborns to 3 years: • Penicillin VK, 125 mg orally twice daily 3 to 5 years: • Penicillin VK, 250 mg orally twice daily 2 years: • 23-valent Streptococcus pneumoniae polysaccharide vaccine (PPV23) Bone marrow aplasia and megaloblastic erythropoiesis 1 mg folic acid daily Stroke Pain episodes Exchange transfusions Hydroxyurea Initiation of treatment: • 10–15 mg/kg/day single daily dose for six to eight weeks Monitor: • complete blood count every two weeks • percent fetal hemoglobin every six to eight weeks • serum chemistries every two to four weeks Diagnosis Screenings for SCD at birth are now performed in most states in the U.S. The presence of hemoglobin S (HbS) with elevated fetal hemoglobin (HbF) and the absence of hemoglobin A indicate either sickle cell anemia or beta thalassemia. It is imperative that sickle cell anemia be detected early, because preventive care must begin by the time a child is two months of age to improve survival. The diagnosis of SCD is usually confirmed by electrophoresis. The sickle cell trait is also identified in screenings of newborns, who have a much lower percentage of hemoglobin S than other patients with SCD. Treatment Options The only cure for SCD is bone marrow transplantation, which usually necessitates a human lymphocyte antigen (HLA)- identical family member donor. There is an 85% diseasefree survival rate, with a 7% transplant-related mortality rate and a 9% graft failure rate.10 Barriers to the widespread use of bone marrow transplantation in patients with SCD include a lack of suitable bone marrow donors and the need to identify patients with an adequate risk-to-benefit ratio. For these reasons, drug therapy for SCD continues to be the primary mode of disease management, focusing on decreasing the complications of this disease (Table 1). Hydroxyurea Hydroxyurea, the only agent that the Food and Drug Administration (FDA) has approved for the management of SCD, is indicated for sickle cell patients who have had at least three painful crises in the previous 12 months. Hydroxyurea prevents the complications of SCD by increasing HbF and total hemoglobin concentrations, by decreasing the adhesion of sickled cells to the endothelium in vitro, and by increasing polymerization time.11 The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) was a randomized, double-blind, placebocontrolled clinical trial in which adult patients were assigned to receive hydroxyurea and placebo. Treatment with hydroxyurea resulted in a 44% difference in the median annual rate of painful crises: 2.5 crises per year in the hydroxyurea arm vs. 4.5 crises per year in the placebo arm. Because hydroxyurea reduced the frequency of episodes of pain, acute chest syndrome, and the need for blood transfusion, the study was stopped four months early.12 A nine-year follow-up of the participants in this trial showed a 40% reduction in mortality rates for patients taking hydroxyurea.13 In small clinical trials of hydroxyurea in children with SCD, the agent was found to be safe and efficacious, and these effects were sustained in long-term trials.14–16 AS AS AA AS AS SS Figure 1 Risk factors. Two parents with the sickle cell trait (AS) have a 25% chance of having a child without the sickle cell trait (AA), a 50% chance of having a child with the sickle cell trait (AS), and a 25% chance of having sickle cell disease (SS). In this inherited condition, both hemoglobin A and S are produced in the red blood cells (more A than S). Vol. 33 No. 4 • April 2008 • P&T® 239
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