Sickle cell anemia

(NEJM 2017;376:1561 & Lancet 2017;390:311)

• Recessive β-globin mutation → structurally abnl hemoglobin (HbS). ~8% African Americans heterozygotes (“sickle trait”; usually w/o sx); ~1/400 homozygotes (sickle cell disease).

• ↓ O2 → HbS polymerizes → RBC sickles, ↓ RBC deformability → hemolysis & microvascular occlusion due to endothelial activ. & PMN adhesion (Blood 2013;122:3892)

• Anemia: chronic hemolysis ± acute aplastic (parvo. B19) or splenic sequestration crises

• Vaso-occlusion & infarction: acute chest syndrome & stroke (high mortality), pulmonary HTN, painful crises, splenic sequestration, renal papillary necrosis, avascular necrosis, dactylitis (hand–foot syndrome), priapism

• Infection: splenic infarction → overwhelming infection by encapsulated organisms; infarcted bone → osteomyelitis (Salmonella, Staph. aureus), can be life threatening

• Diagnosis: sickle-shaped RBCs and Howell-Jolly bodies on smear; Hb electrophoresis

• Treatment: hydroxyurea, folic acid; voxelotor (Hgb S polymerization inhibitor) ↓ hemolysis & ↑ Hgb (NEJM 2019;381:509)

• Vaccines: pneumo, meningo, H flu, HBV

• Pain & vaso-occlusive crises: analgesia (consider PCA; ask Pt what worked prev.), IVF, transfusion only if sx & Hgb below Pt’s baseline (often low) given alloimmunization & Fe accumulation (need chelation); Ppx w/ crizanlizumab (anti-P-selectin; NEJM 2017;376:429)

• Acute chest (fever, ↑ WBC, pulm. infilt., r/o other causes): O2, abx, IVF, exchange txfusion

• TIA/stroke: often exchange transfusion (goal Hgb 10) ± thrombolytics

• Gene therapy in development (NEJM 2021;384:205)