From the Guidelines
Additional Tests for Suspected Hemolytic Anemia
The patient with suspected hemolytic anemia characterized by hyperbilirubinemia, macrocytosis, and an elevated reticulocyte count should undergo comprehensive diagnostic workup including history and physical examination, blood chemistry, CBC with peripheral smear, LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin 1.
- Key tests include:
- Autoimmune serology to evaluate for autoimmune causes of hemolysis
- Paroxysmal nocturnal hemoglobinuria (PNH) screening to rule out PNH
- Direct and indirect bilirubin, direct agglutinin test, and bone marrow analysis if no obvious cause is found
- Evaluation for viral or bacterial causes of hemolysis, including mycoplasma
- Protein electrophoresis and cryoglobulin analysis
- Glucose-6-phosphate dehydrogenase level to assess for G6PD deficiency
- Assessment of methemoglobinemia
- It is also essential to evaluate for common drug causes of hemolysis, such as ribavirin, rifampin, dapsone, and NSAIDs 1.
- If the patient is refractory, work-up for bone marrow failure syndrome should be considered, including B12, folate, copper, parvovirus, iron, thyroid, and infection evaluation 1.
From the Research
Diagnostic Approach
To diagnose hemolytic anemia characterized by hyperbilirubinemia, macrocytosis, and an elevated reticulocyte count, the following tests are indicated:
- Reticulocyte count to confirm reticulocytosis 2, 3
- Peripheral blood smear to identify abnormalities in red blood cell morphology 2, 4, 5
- Measurement of unconjugated bilirubin and lactate dehydrogenase to assess the degree of hemolysis 2, 6, 5
- Direct antiglobulin test to detect anti-erythrocyte antibodies 4
- Haptoglobin levels to confirm decreased haptoglobin 2, 5
Additional Tests
Based on the initial findings, additional tests may be necessary to determine the underlying cause of hemolytic anemia, including:
- Genetic testing, such as Sanger sequencing or next-generation sequencing, to identify genetic causes of hemolytic anemia 3
- Erythrocyte adenylate kinase (EAK) levels to confirm the presence of hemolysis 6
- Tests to rule out other conditions, such as liver disease or myocardial infarction, that may cause similar laboratory findings 6
Specific Conditions
Certain conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis, may require specific diagnostic tests and management strategies 5