Snapshot A 8-year-old African American boy presents with his mother to urgent care for severe pain in his hands and feet. He reports that he has had on and off pain for as long as he can remember, but this time the pain is unremitting and not responsive to pain medications at home. He had been playing outside in the snow when the pain started. His past medical history includes a blood disorder but his parents cannot remember what this was called, as it was diagnosed in a foreign hospital. On physical exam, he is noted to be pale and he has palpable splenomegaly. A peripheral blood smear shows sickled red blood cells. He is started on intravenous pain medications. 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) login to view 1 more bullet heterozygotes (HbSA) login to view 2 more bullets hemoglobin SC disease (HbSC) login to view 3 more bullets Genetics inheritance pattern autosomal recessive mutations chromosome 11 ß-globin gene Epidemiology Demographics blacks are most commonly affected Risk factors family history ETIOLOGY 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 login to view 2 more bullets clinical severity is determined by presence of other Hb mutations sickled RBCs undergoes hemolysis every 17 days (1/7th that of normal RBC lifespan) login to view 1 more bullet sickled RBCs have a tendency to aggregate in the microvascular circulation, which can lead to: login to view 1 more bullet Presentation Clinical presentation acute events anemia vaso-occlusive events login to view 18 more bullets chronic events pain hemolytic anemia login to view 1 more bullet neurologic deficits stunted growth and development renal disease login to view 3 more bullets 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 Serum labs decreased hemoglobin and hematocrit increased reticulocyte count mildly elevated fetal hemoglobin (HbF) 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 login to view 4 more bullets Medical supportive care indications login to view 1 more bullet modalities login to view 3 more bullets exchange transfusion indications login to view 1 more bullet hydroxyurea indications login to view 2 more bullets 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 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 Acute sickle hepatic crisis secondary to occlusion the hepatic sinusoids associated with an increased mortality in the mother and fetus Prognosis Overall survival is reduced Prognosis is better with comprehensive care and clinical monitoring