Sickle Cell Anemia - Hematology

Snapshot
A 4-year-old African American boy presents to the emergency room for sudden onset severe abdominal pain. He has a history of sickle cell anemia. On physical exam, he is pale, and he has a left upper quadrant palpable mass. Complete blood count is significant for hemoglobin of 7.3 g/dL. Serum unconjugated bilirubin and reticulocyte count are elevated. (Acute splenic sequestration)
Introduction

Overview sickle cell anemia is an autosomal recessive disease that results in abnormal hemoglobin characterized by hemoglobin S (HbS), resulting in hemolytic anemia and vaso-occlusion sickle cell disease is an overarching term including sickle cell anemia, as well as patients with a sickle mutation (HbS) and a different mutation in the ß-globin gene (e.g., ß-thalassemia or hemoglobin C disease) homozygosity (HbSS) sickle cell anemia heterozygotes (HbSA) sickle cell trait, usually asymptomatic and may confer some resistance to malaria may have painless hematuria as a result of renal papillary necrosis hemoglobin SC disease (HbSC) HbS and HbC hemoglobin C disease (HbC) point mutation in ß-globin gene where glutamic acid is replaced with lysine Epidemiology demographics blacks are most commonly affected risk factors family history Pathogenesis pathophysiology recall that hemoglobin (Hb) is a soluble tetramer composed of 2 α-globins and 2 ß-globins HbS results from point mutation of ß-globin gene that substitutes valine for glutamic acid due to hydrophobic interactions from valine, hemoglobin can polymerize in red blood cells this makes the hemoglobin tetramer poorly soluble and results in distortion of red blood cells (RBCs) into a sickle shape this form causes vaso-occlusion clinical severity is determined by presence of other Hb mutations elevated 2,3-diphosphoglycerate sickled RBCs undergoes hemolysis every 17 days (1/7^th that of normal RBC lifespan) hemolysis generates reactive oxygen species Genetics inheritance pattern autosomal recessive mutations chromosome 11 ß-globin gene Prognosis overall survival is reduced prognosis is better with comprehensive care and clinical monitoring
Presentation
Clinical presentation acute events anemia vaso-occlusive events acute painful episodes previously called “sickle cell crises” may occur on top of chronic pain triggers include cold temperature, stress, alcohol, and menses dactylitis acute pain in hands and feet particularly common in children acute chest syndrome cerebrovascular accidents myocardial infarction priapism renal infarction splenic infarction by 2-4 years of age, patients have functional asplenia venous thromboembolism chronic events pain hemolytic anemia contributing factors include low erythropoietin concentration (can be due to renal disease) and folate deficiency neurologic deficits stunted growth and development renal disease painless hematuria due to papillary infarcts medication toxicities urinary concentrating defect Physical exam splenomegaly jaundice pallor bone/joint tenderness
Imaging
Radiographs indications acute chest syndrome findings new pulmonary infiltrate of one or more lung segments
Studies
Prenatal testing currently not routinely used Newborn screening methodology varies by state but can be detected via high performance liquid chromatography (preferred), tandem mass spectrometry, DNA testing, or isoelectric focusing (gel electrophoresis) Serum labs decreased hemoglobin and hematocrit increased reticulocyte count decreased haptoglobin dramatically increased hemoglobin S (HbS) ~ 80% elevated fetal hemoglobin as well (HbF) ~ 16% normocytic anemia Peripheral blood smear Howell-Jolly bodies nuclear remnants of RBCs that have not been phagocytosed due to functional asplenia sickled cells
Differential
ß-thalassemia key distinguishing factors microcytic anemia no sickle cells on peripheral blood smear
Treatment
Lifestyle prophylactic treatments modalities daily folic acid penicillin until 5 years of age pneumococcal vaccine prevents pneumococcal sepsis Medical supportive care indications acute attacks modalities hydration oxygen analgesia exchange transfusion indications acute vaso-occlusive events hydroxyurea indications decreases frequency and severity of attacks increases production of fetal hemoglobin, which has a higher affinity for oxygen may consider addition of Gardos channel blocking agent prevents RBC dehydration by inhibiting K+ efflux Surgical hematopoietic cell transplantation indications the only curative treatment
Complications
Functional asplenia by an early age at increased risk for encapsulated bacterial infection (e.g., Streptococcus and Salmonella) may result in splenic sequestration of RBCs and extravascular hemolysis Aplastic crisis associated with parvovirus B19 infection or splenic sequestration crisis low reticulocyte count supplement with daily folic acid Chronic lung disease and pulmonary hypertention secondary to acute chest syndrome Renal disease can present as inability to concentrate urine, resulting in frequent urination Retinopathy secondary to retinal artery occlusion Cardiomyopathy left-sided diastolic dysfunction with or without pulmonary hypertension due to pulmonary hypertension, chronic anemia and hypoxemia with increased cardiac output, transfusion overload, and hypertension Cholelithiasis secondary to chronic hemolysis