hemolysis

Hemolysis is the destruction of red blood cells (RBCs) leading to the release of hemoglobin into plasma and a reduction in circulating RBCs. It can occur intravascularly, within blood vessels, or extravascularly, mainly in the spleen and liver. In intravascular hemolysis, free hemoglobin binds to haptoglobin and, if overwhelmed, appears in plasma and urine, while plasma haptoglobin levels fall. Extravascular hemolysis involves phagocytosis of RBCs by macrophages with less free hemoglobin but increased bilirubin.

Causes of hemolysis are diverse and are often categorized as physiological or pathological. Pathological hemolysis may be immune-mediated (autoimmune hemolytic anemia, alloimmune reactions after transfusion or hemolytic disease of the newborn, drug-induced), mechanical (prosthetic heart valves, microangiopathic processes such as thrombotic microangiopathy), infectious (malaria), chemical or toxic (lead, certain drugs, venom), or hereditary (RBC membrane disorders such as spherocytosis or elliptocytosis; enzymopathies like G6PD deficiency; hemoglobinopathies such as sickle cell disease).

Clinical features include pallor, fatigue, jaundice, and dark urine from hemoglobin or bilirubin. Chronic hemolysis may cause iron deficiency and pigment gallstones. Laboratory findings depend on the mechanism: anemia with reticulocytosis; elevated LDH and indirect bilirubin; decreased haptoglobin in intravascular hemolysis; possible hemoglobinemia or hemoglobinuria; and peripheral blood smear findings such as schistocytes (microangiopathic), spherocytes (hereditary spherocytosis or autoimmune hemolysis), or bite cells (G6PD deficiency). A direct antiglobulin test (Coombs test) helps identify immune causes and is typically positive in autoimmune and alloimmune hemolysis.

Treatment targets the underlying cause and provides supportive care. This may include transfusion for symptomatic anemia, stopping offending drugs, corticosteroids or immunosuppressants for autoimmune forms, splenectomy for certain membrane disorders, rituximab for AIHA, and complement inhibition (e.g., eculizumab) for paroxysmal nocturnal hemoglobinuria. Monitoring and management of complications such as iron overload, iron deficiency, and pigment gallstones are important.