From the Guidelines
To diagnose hemolysis, the most critical laboratory tests include CBC with evidence of anemia, macrocytosis, and evidence of hemolysis on peripheral smear, as well as LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin, as recommended in the 2021 ASCO guideline update 1. When evaluating a patient for hemolysis, it is essential to consider a comprehensive workup, including:
- History and physical examination to identify potential causes such as new drugs, insect bites, or infections
- Blood chemistry and CBC to assess for anemia and macrocytosis
- Peripheral smear to directly visualize evidence of hemolysis
- LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin to confirm hemolysis and assess its severity Additional tests may be necessary to determine the underlying cause of hemolysis, such as:
- Direct and indirect bilirubin to evaluate liver function
- Direct agglutinin test (DAT or Coombs test) to detect immune-mediated hemolysis
- PNH screening and bone marrow analysis to evaluate for bone marrow failure syndromes
- Evaluation for viral or bacterial causes of hemolysis, including mycoplasma and other infections
- Glucose-6-phosphate dehydrogenase level to assess for G6PD deficiency
- Assessment of common drug causes of hemolysis, such as ribavirin, rifampin, and NSAIDs, as outlined in the 2021 ASCO guideline update 1.
From the Research
Laboratory Tests for Diagnosing Hemolysis
The following laboratory tests are used to diagnose hemolysis:
- Reticulocytosis, which indicates an increase in immature red blood cells [ 2, 3, 4, 5 ]
- Increased lactate dehydrogenase (LDH), a marker of intravascular hemolysis [ 2, 3, 4 ]
- Increased unconjugated bilirubin, which can indicate hemolysis [ 2, 3, 4 ]
- Decreased haptoglobin levels, which can indicate hemolysis [ 2, 3, 4 ]
- Peripheral blood smear findings, which can help identify abnormal red blood cell morphologies [ 2, 3, 4 ]
- Direct antiglobulin test, which can help differentiate immune causes from nonimmune causes [ 2, 3, 4 ]
- Serum erythrocyte adenylate kinase (EAK) levels, which can be used to diagnose hemolysis [ 6 ]
- Genetic testing, such as Sanger sequencing or next-generation sequencing, which can be used to diagnose underlying genetic causes of hemolysis [ 5 ]
Additional Tests
Additional tests that may be used to diagnose hemolysis include:
- Hemoglobin levels, which can help define the clinical severity of hemolysis [ 4 ]
- Thrombocytopenia, which can suggest a possible thrombotic microangiopathy or Evans' syndrome [ 4 ]
- Hemosiderinuria, which can indicate intravascular hemolysis [ 4 ]
- Hyperferritinemia, which can be associated with chronic hemolysis [ 4 ]