Common causes of hemolysis and hemolytic anemia in adults

Nonimmune causes

Hereditary

Enzyme deficiencies (G6PD, PK, 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

Thrombotic microangiopathies (TTP, HUS, CM-TMA, DITMA)

MDS (especially acquired mutations in EZH2 and U2AF1)

Mechanical RBC destruction (aortic stenosis, prosthetic valve leak)

Immune causes

Warm AIHA

Drug-induced immune hemolysis

Hemolytic transfusion reactions (ABO incompatibility, alloantibodies)

Paroxysmal cold hemoglobinuria (PCH)

Paroxysmal nocturnal hemoglobinuria (PNH)

Cold agglutinin disease (CAD)

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).

AIHA: autoimmune hemolytic anemia; CM-TMA: complement-mediated thrombotic microangiopathy; DITMA: drug-induced thrombotic microangiopathy; G6PD: glucose-6-phosphate dehydrogenase; HUS: hemolytic uremic syndrome; MDS: myelodysplastic syndrome; PK: pyruvate kinase; TTP: thrombotic thrombocytopenic purpura.

Graphic 72394 Version 21.0

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Common causes of hemolysis and hemolytic anemia in adults