Diagnosis of hereditary red blood cell (RBC) disorders associated with hemolysis or hemolytic anemia

DAT: direct antiglobulin test (direct Coombs test); G6PD: glucose-6-phosphate dehydrogenase; PK: pyruvate kinase; PNH: paroxysmal nocturnal hemoglobinuria; RBC: red blood cell; CBC: complete blood count; AIHA: autoimmune hemolytic anemia; LDH: lactate dehydrogenase.

• Increased reticulocyte count.
• High LDH and low haptoglobin (especially when a component of intravascular hemolysis is present); high bilirubin.
• Negative direct antiglobulin test (DAT; Coombs test).

The rest of the CBC is typically normal. If there is new onset hemolytic anemia and/or other cytopenias, the differential diagnosis expands to include disorders such as paroxysmal nocturnal hemoglobinuria (PNH).

¶ Up to 5 to 10% of AIHA is DAT-negative and requires more specialized testing. Refer to UpToDate for discussions of rare RBC enzyme disorders.

• Testing for a known familial condition if a relative has already been diagnosed with a specific disorder; this includes prenatal diagnosis of PK deficiency and evaluation of severe anemia in utero.
• Testing for a different enzyme disorder based on clinical presentation.
• Using genetic testing first, followed by enzyme activity if appropriate.

If initial testing is negative, evaluate for other disorders with the help of an expert in RBC enzyme disorders.