Common causes of hemolysis and hemolytic anemia in adults

Nonimmune causes

Hereditary

Enzyme deficiencies (deficiencies of G6PD, pyruvate kinase, glucose-phosphate isomerase, 5' nucleotidase)

Hemoglobinopathies (sickle cell disease, thalassemias, unstable hemoglobins)

Membrane disorders (hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis)

Acquired

Liver disease

Hypersplenism

Infections (Bartonella, clostridial sepsis, malaria, babesiosis)

Oxidant agents (dapsone, nitrites, aniline dyes)

Toxins (lead, copper, snake and spider bites)

Infusion of a hypotonic solution

Microangiopathic hemolytic anemia (TTP, HUS, complement-mediated TMA, drug-induced TMA, aortic stenosis, prosthetic valve leak)

Immune causes

Warm autoimmune hemolytic anemia (warm AIHA)

Drug-induced immune hemolysis

Hemolytic transfusion reactions (ABO incompatibility, alloantibodies)

Paroxysmal cold hemoglobinuria (PCH)

Paroxysmal nocturnal hemoglobinuria (PNH)

Cold agglutinin disease

Intravenous immune globulin (IVIG) or anti-RhD immune globulin

Nonimmune causes generally have a negative Coombs test (negative direct antiglobulin test [DAT]); immune causes are typically DAT-positive. Refer to UpToDate for an approach to the evaluation. Any hemolytic anemia can lead to an underestimation of the hemoglobin A1C (HbA1C).

G6PD: glucose-6-phosphate dehydrogenase; TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic syndrome; TMA: thrombotic microangiopathy.

Graphic 72394 Version 18.0

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Common causes of hemolysis and hemolytic anemia in adults