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Acquired hemolytic anemias are disorders characterized by hemolysis of red blood cells (RBCs) not due to congenital or inherited disorders of hemoglobin synthesis or of the RBC membrane. Hemolysis of RBCs can take place within the intravascular space or in the extravascular spaces of the spleen and liver and can produce a spectrum of disease from mild, asymptomatic illness to severe hemodynamic compromise leading to critical ED encounters.

Clinical features of hemolytic anemia include those common to anemia in general: weakness, dizziness, shortness of breath, tachycardia, palpitations, chest pain, new or accentuated cardiac murmur, and pallor. RBC destruction generates free hemoglobin that is then broken down into bilirubin. Jaundice and darkened urine may develop when bilirubin production exceeds the liver’s ability to conjugate it for biliary and fecal excretion. Splenic enlargement may promote the storage and extravascular breakdown of RBCs.

Characteristic laboratory findings of acquired hemolytic anemia demonstrate hemolysis of RBCs, hemoglobin breakdown, and compensatory RBC production (Table 237-1).

TABLE 237-1Basic Tests and Findings in the Evaluation of Hemolytic Anemia


Immune-mediated acquired hemolytic anemia encompasses three main categories: autoimmune, alloimmune, and drug induced.


Individuals with autoimmune hemolytic anemia make antibodies against their own RBCs.1,2 Diagnosis requires evidence of an antibody on the patient’s RBCs, usually accompanied by an autoantibody in the plasma. The direct antigen test, also known as the direct Coombs test, is performed by combining the patient’s anticoagulated, washed RBCs with anti–immunoglobulin G and anti-C3d (complement) antibodies to detect the presence of immunoglobulin G and/or complement on the RBC surface. A positive direct antigen test consists of the detection of either immunoglobulin G or complement on the RBC surface; it does not require the detection of both. A positive direct antigen test is not specific for a diagnosis of autoimmune hemolytic anemia (Table 237-2), nor does the presence of immunoglobulin G and/or complement on a patient’s RBCs indicate the severity of disease; the direct antigen test is, however, a critical confirmatory screen. The indirect Coombs test looks for the presence of autoantibodies in the patient’s serum, testing against a panel of RBCs bearing specific ...

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