hematology and oncology
Sickle Cell Disease
Treatment of Sickle Cell Disease
Broad-spectrum antibiotics (for infection) Analgesics and IV hydration (for vaso-occlusive pain crisis) Oxygen (for hypoxia) Sometimes transfusions Immunizations,folic acidsupplementation, andhydroxyurea(for health maintenance) Stem cell transplantation (for advanced complications) Treatment includes regular health maintenance measures as well as specific treatment of the complications as they arise. Complications are treated supportively. No effective in vivo anti-sickling drug is available. Splenectomy is valueless. Indications for hospitalization include suspected serious (including systemic) infection, aplastic crisis, acute chest syndrome, and, often, intractable pain or the need for transfusion. Fever alone may not be a reason to hospitalize. However, patients who appear acutely ill and have a temperature>38°C should be admitted so that cultures can be obtained and IV antibiotics can be given. Patients with suspected serious bacterial infections or acute chest syndrome require broad-spectrum antibiotics immediately. Painful crises are managed with liberal administration of analgesics, usually opioids. IVmorphine(continuous or bolus) is effective and safe;meperidineis avoided. During crises, pain and fever may persist for as long as 5 days. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often useful in reducing opioid requirements; however, they must be used cautiously in patients with renal disease. Although dehydration contributes to sickling and may precipitate crises, it is unclear whether vigorous hydration is helpful during crises. Nevertheless, maintaining normal intravascular volume has been a mainstay of therapy. Oxygen is given if needed to treat hypoxia. Transfusion is given in many situations in which its efficacy has not been demonstrated. However, chronic transfusion therapy is indicated for prevention of recurrent cerebral thrombosis, especially in children, in an effort to maintain the Hb S percentage less than 30%. In the acute setting, specific indications for transfusion include Acute splenic sequestration Aplastic crises Cardiopulmonary symptoms or signs (eg, high-output heart failure, hypoxemia with PO2<65 mm Hg) Preoperative use Priapism Life-threatening events that would benefit from improved oxygen delivery (eg, sepsis, severe infection, acute chest syndrome, stroke, acute organ ischemia) Sometimes pregnancy Transfusion is not helpful during an uncomplicated painful crisis. Simple transfusion can be done when the goal is to correct anemia, such as during aplastic crisis or splenic or hepatic sequestration. Exchange transfusion is done during severe acute events such as the acute chest syndrome or stroke in order to decrease the Hb S percentage and prevent ischemia. It can be done with modern apheresis machines. If the initial hemoglobin is low (<7 g/dL [<70 g/L]), this process cannot be initiated before first transfusing red cells. Partial exchange transfusion minimizes iron accumulation and hyperviscosity. Hematopoietic Stem Cell Transplantation remains the only curative treatment for sickle cell disease. Given the risks associated with this therapy, it is generally restricted to patients with advanced disease complications. Gene therapy or gene editing techniques that reduce the amount of Hb S are currently in clinical trials. This field is rapidly evolving and use of stem cell therapy to treat sickle cell disease will likely expand in the near future. For long-term management the following interventions have reduced mortality, particularly during childhood: Pneumococcal,Haemophilus influenzaeinfluenza (inactivated, not live), and meningococcal vaccines Early identification and treatment of serious bacterial infections Prophylactic antibiotics, including continuous prophylaxis with oral penicillin from age 4 months to 6 year Use ofhydroxyureaand folate supplementation Supplementalfolic acid, 1 mg orally once a day, is usually prescribed. Hydroxyurea, by increasing Hb F and thereby reducing sickling, decreases painful crises (by 50%) and decreases acute chest syndrome and transfusion requirements. It is indicated in patients with recurrent pain crises or other complications. The dose ofhydroxyureais variable and is adjusted based on blood counts and adverse effects.Hydroxyureacauses neutropenia and thrombocytopenia. It is also a teratogen and should not be given to females of child-bearing age. target vaso-occlusion and were found to decrease pain crises in controlled, randomized studies ( Treatment references ). Transcranial Doppler flow studies in children can help predict risk of stroke, and many experts recommend annual screening for children from age 2 to 16 years. Children at high risk appear to benefit from prophylactic, chronic exchange transfusions to keep Hb S at < 30% of total hemoglobin; Secondary Iron Overload is common and must be screened for and treated. For patients receiving frequent red cell transfusions, chelation therapy to prevent or delay complications due to iron overload should be considered. 1.Ataga KI, Kutlar A, Kanter J, et al:Crizanlizumabfor the prevention of pain crises in sickle cell disease.N Engl J Med376(5):429–439, 2017. doi: 10.1056/NEJMoa1611770 2.Niihara Y, Miller ST, Kanter J, et al: A phase 3 trial ofl-glutaminein sickle cell disease.N Engl J Med379(3):226–235, 2018. doi: 10.1056/NEJMoa1715971 3.Vichinsky E, Hoppe CC, Ataga KI, et al: A phase 3 randomized trial ofvoxelotorin sickle cell disease.N Engl J Med381(6):509–519, 2019. doi: 10.1056/NEJMoa1903212 