What is the initial workup and treatment for a patient with hemolytic anemia?

Diagnostic Workup and Management of Hemolytic Anemia

The initial workup for hemolytic anemia must include CBC with peripheral blood smear, reticulocyte count, LDH, haptoglobin, bilirubin (direct and indirect), and direct antiglobulin test (DAT/Coombs test) to establish the presence and type of hemolysis. 1

Initial Diagnostic Evaluation

Laboratory Tests

• Complete blood count (CBC) with red cell indices
• Peripheral blood smear examination (looking for spherocytes, schistocytes, or other abnormal morphologies)
• Reticulocyte count
• Lactate dehydrogenase (LDH)
• Haptoglobin
• Bilirubin (direct and indirect)
• Direct antiglobulin test (DAT/Coombs test)
• Disseminated intravascular coagulation (DIC) panel (PT/INR, PTT, fibrinogen) 2, 1

Additional Testing Based on Initial Results

• Autoimmune serology
• Paroxysmal nocturnal hemoglobinuria (PNH) screening
• Glucose-6-phosphate dehydrogenase (G6PD) level
• Protein electrophoresis and cryoglobulin analysis
• Evaluation for viral/bacterial causes (mycoplasma, EBV, CMV)
• If microangiopathic hemolytic anemia is suspected: ADAMTS13 activity and inhibitor titer 2, 1

Diagnostic Algorithm

1. Confirm hemolysis: Elevated LDH, decreased haptoglobin, elevated indirect bilirubin, and reticulocytosis

2. Determine if immune or non-immune:

   • Positive DAT → Immune-mediated hemolysis
   • Negative DAT → Non-immune hemolysis

3. If immune-mediated:

   • Warm antibody (IgG) → Warm autoimmune hemolytic anemia
   • Cold antibody (IgM) → Cold agglutinin disease
   • Mixed antibody → Mixed-type autoimmune hemolytic anemia

4. If non-immune:

   • Examine peripheral smear:
     • Spherocytes → Hereditary spherocytosis or other membranopathies
     • Schistocytes → Microangiopathic hemolytic anemia (TTP, HUS, DIC)
     • Normal morphology → Consider enzymopathies (G6PD deficiency), mechanical hemolysis, or drug-induced hemolysis 1, 3, 4

Management Based on Severity

Grade 1 (Mild Hemolysis)

• Continue close clinical follow-up and laboratory evaluation
• Supplementation with folic acid 1 mg daily 2

Grade 2 (Moderate Hemolysis)

• If immune-mediated: Prednisone 0.5-1 mg/kg/day
• Monitor hemoglobin levels weekly until stable 2

Grade 3 (Severe Hemolysis)

• Consider hospital admission based on clinical judgment
• Obtain hematology consultation
• If immune-mediated: Prednisone 1-2 mg/kg/day (oral or IV depending on severity)
• RBC transfusion to maintain hemoglobin 7-8 g/dL (avoid overtransfusion)
• Folic acid supplementation 1 mg daily 2

Grade 4 (Life-threatening Hemolysis)

• Immediate hospital admission
• Urgent hematology consultation
• IV prednisone 1-2 mg/kg/day
• For refractory immune hemolysis: Consider rituximab, IVIG, cyclosporin A, or mycophenolate mofetil
• RBC transfusion as needed (coordinate with blood bank) 2

Special Considerations

Thrombotic Thrombocytopenic Purpura (TTP)

If TTP is suspected (schistocytes, severe thrombocytopenia, neurological symptoms):

• Immediate hematology consultation
• Plasma exchange according to established guidelines
• Consider rituximab 2

Drug-Induced Hemolysis

• Evaluate for common drug causes: ribavirin, rifampin, dapsone, interferon, cephalosporins, penicillins, NSAIDs, quinine/quinidine, fludarabine, ciprofloxacin, lorazepam, diclofenac, hydroxyurea 2, 5
• Discontinue suspected causative medications

Common Pitfalls to Avoid

• Overlooking drug-induced hemolysis
• Failing to check reticulocyte count (inadequate reticulocytosis may indicate bone marrow involvement or iron/vitamin deficiency)
• Missing microangiopathic hemolytic anemia (requires urgent intervention)
• Confusing hemolytic anemia with other causes of elevated LDH or bilirubin 1, 4

Monitoring

• Monitor hemoglobin levels weekly until the condition stabilizes or corticosteroid tapering is complete
• Follow LDH, haptoglobin, and bilirubin to assess response to treatment
• Adjust therapy based on clinical response and laboratory parameters 2