Sickle cell anemia is caused by a recessive beta-globin mutation leads to structurally abnormal hemoglobin (HbS). 8% of African Americans are heterozygotes (“sickle trait”; usually w/o sx). 1 in 400 are homozygotes (sickle cell disease)
Deoxygenated HbS polymerizes leading to RBC sickles and decreased RBC deformability which in turn leads to hemolysis and microvascular occlusion
Anemia is caused by chronic hemolysis +/- acute aplastic (parvo. B19) or splenic sequestration crises.
Vaso-occlusion and infarction lead to painful crises, acute chest syndrome, CVA, splenic sequestration, hand-foot syndrome, renal papillary necrosis, aseptic necrosis, priapism
Infection: splenic infarction leads to overwhelming infection by encapsulated organisms; infarcted bone leads to osteomyelitis (Salmonella, Staph. aureus).
Clinical Manifestations of Sickle Cell Anemia
| Acute | Chronic | |
| Pain | Acute vasoocclusive pain episodes, acute chest syndrome | Pain from tissue infarction, osteonecrosis, ulcers |
| Infection | Sepsis, pneumonia, meningitis | Leg ulcers, osteomyelitis |
| Anemia | Aplastic crisis, splenic sequestration crisis, hyperhemolytic crisis | Compensated hemolytic anemia, chronic hypersplenism |
| CNS | Ischemic stroke, hemorrhagic stroke, seizures, TIA | Silent cerebral infarctions, cognitive delay, behavioral issues |
| Pulmonary | Acute chest syndrome, asthma, pulmonary fat embolism, pulmonary thromboembolism | Pulmonary hypertension, sleep disordered breathing, chronic restrictive lung disease |
| Renal | Renal infarction, medication toxicity, hematuria, acute renal failure, acute nephrotic syndrome | Hypertension, chronic renal failure, concentrating defect, nephrogenic diabetes insipidus, renal medullary carcinoma |
| Skeletal | Dactylitis, avascular necrosis | Osteoporosis, osteomyelitis |
| Cardiac | Myocardial infarction, dysrhythmia, sudden death, autonomic dysfunction | Diastolic dysfunction, heart failure |
| Hepatobiliary | Hepatic sequestration crisis, cholecystitis, liver injury, acute intrahepatic cholestasis | Pigment gallstones |
| Ocular | Retinal artery occlusion, hyphema, retinal detachment | Proliferative retinopathy, blindness |
| Obstetric | Fetal and maternal complications | |
| Genitourinary | Priapism | Erectile dysfunction |
| Endocrine | Delayed puberty, reduced growth | |
| Other | Venous thromboembolism | Functional asplenia |
From uptodate.com