What is the appropriate management for a patient with Mycoplasma pneumonia, severe anemia, elevated reticulocyte count, and low Haptoglobin?

Management of Mycoplasma-Induced Hemolytic Anemia

Stop the antibiotics immediately and initiate high-dose corticosteroids (prednisone 1-2 mg/kg/day orally or IV methylprednisolone if severe symptoms develop); rituximab is NOT indicated as first-line therapy for this acute cold agglutinin-mediated hemolytic anemia. 1, 2

Clinical Reasoning

This patient has developed cold agglutinin disease (CAD) secondary to Mycoplasma pneumoniae infection, evidenced by:

• Severe anemia (Hb 60 g/L) with active hemolysis 2
• Elevated reticulocytes and LDH with undetectable haptoglobin (0.3) 1, 2
• Normal platelets and WBC (excluding TTP/HUS or DIC) 1
• Temporal relationship to Mycoplasma infection 3, 4, 5

The yellowing of eyes (jaundice) with normal LFTs confirms hemolytic rather than hepatic pathology. 1

Immediate Management Algorithm

Step 1: Discontinue Potential Triggers

• Stop all antibiotics temporarily - while antibiotics don't cause the hemolysis, cold agglutinin disease can persist or worsen regardless of antibiotic continuation 1
• Evaluate if macrolide antibiotics were used (common for Mycoplasma) and consider drug-induced hemolysis in differential 1, 2

Step 2: Grade the Severity

This patient has Grade 3 hemolytic anemia (Hb <8.0 g/dL or <80 g/L), requiring aggressive intervention 1, 2

Step 3: Initiate Corticosteroid Therapy

• Start prednisone 1-2 mg/kg/day orally (or IV methylprednisolone if unable to take oral medications) 1, 2
• Expected response rate is 70-80% for autoimmune hemolytic anemia 2
• Mycoplasma-associated cold agglutinin hemolysis typically responds well to corticosteroids 3, 5

Step 4: Supportive Measures

• Folic acid 1 mg daily to support erythropoiesis 1, 2
• Avoid cold exposure - critical in cold agglutinin disease as cold triggers hemolysis 3
• Keep patient warm (room temperature >37°C, warm IV fluids) 3
• Consider RBC transfusion ONLY if symptomatic or Hb <7-8 g/dL; use blood warmer if transfusing 1, 2

Why NOT Rituximab First-Line?

Rituximab is reserved for refractory cases, not acute Mycoplasma-induced hemolysis 2. The evidence shows:

• Mycoplasma-associated hemolysis is typically self-limited and steroid-responsive 3, 5, 6
• Cold agglutinins in Mycoplasma infection are transient, resolving with treatment of underlying infection 3, 4
• Rituximab takes weeks to work and carries significant immunosuppression risks 2
• Case reports demonstrate excellent response to corticosteroids alone in Mycoplasma-CAD 3, 5

Monitoring Protocol

• Check hemoglobin weekly until steroid taper begins 2
• Monitor for steroid complications: hyperglycemia, hypertension, mood changes, insomnia 2
• Repeat cold agglutinin titer in 2-4 weeks (should decrease as Mycoplasma resolves) 3, 4
• If no improvement in 1-2 weeks, add IVIG 0.4-1 g/kg/day for 3-5 days 2

When to Consider Rituximab

Only escalate to rituximab if: 2

• No response to corticosteroids after 2 weeks
• IVIG failure
• Steroid-dependent hemolysis requiring >10-15 mg/day prednisone for >3 months
• Recurrent severe hemolysis after steroid taper

Critical Pitfalls to Avoid

• Do NOT delay corticosteroids - severe hemolysis (Hb 60 g/L) increases mortality risk 2
• Do NOT transfuse aggressively - transfuse only minimum units needed for symptoms, as transfused cells will also hemolyze 1, 2
• Do NOT use cold blood products - always use blood warmer in CAD 3
• Do NOT assume observation is safe at this hemoglobin level - Grade 3 anemia requires intervention 1, 2
• Watch for thrombotic complications - rare but reported with Mycoplasma-CAD (arterial thrombosis documented) 4

Antibiotic Resumption

Once hemolysis stabilizes on corticosteroids (typically 3-5 days), resume macrolide antibiotics (azithromycin or doxycycline) to complete Mycoplasma treatment 1, 6. The hemolysis is immune-mediated, not antibiotic-induced, but completing antimicrobial therapy helps resolve the underlying trigger. 3, 5, 6