Hemolytic anemia

Hemolytic anemia is a group of disorders in which red blood cells are destroyed faster than the bone marrow can replace them. Normal red cells live about 120 days; in hemolysis their lifespan is sharply shortened, and when marrow compensation falls behind, anemia develops.

Hemolysis occurs in two patterns. Intravascular hemolysis destroys cells within the bloodstream, releasing free hemoglobin — seen in mechanical valve shear, ABO-incompatible transfusion reactions, and paroxysmal nocturnal hemoglobinuria. Extravascular hemolysis, the more common pattern, occurs when macrophages in the spleen and liver remove abnormal or antibody-coated cells, as in hereditary spherocytosis and most autoimmune hemolytic anemias. Laboratory clues are shared: elevated lactate dehydrogenase (LDH), elevated indirect bilirubin, decreased haptoglobin (most marked in intravascular hemolysis), and a high reticulocyte count as the marrow pushes out young red cells. The peripheral smear often points to the cause — spherocytes, schistocytes, sickle cells, or bite cells.

Causes divide into inherited defects and acquired processes. Inherited forms include membrane defects (hereditary spherocytosis), enzyme deficiencies (G6PD deficiency, often triggered by oxidant drugs or fava beans), and hemoglobinopathies (sickle cell disease, thalassemia). Acquired forms include autoimmune hemolysis, mechanical destruction, infections such as malaria, and drug reactions — including immune hemolysis associated with certain antibiotics like penicillins and cephalosporins.

USMLE Step 1 tests hemolytic anemias heavily in hematology, expecting you to match smear findings, labs, and Coombs test results to specific causes. The PTCE touches the concept through drug-induced hemolysis as an adverse effect of antibiotics.