Microangiopathic Hemolytic Anemia (MAHA) with Thrombotic Microangiopathy (TMA)
This patient has microangiopathic hemolytic anemia (MAHA) with thrombotic microangiopathy (TMA), evidenced by schistocytes on peripheral smear, anemia with elevated reticulocyte count (1.3%), and normal iron stores (ferritin 120). 1
Diagnostic Reasoning
The presence of schistocytes is pathognomonic for microangiopathic hemolytic anemia, indicating mechanical fragmentation of red blood cells within the circulation 1, 2. The elevated reticulocyte count (1.3%) confirms an appropriate bone marrow response to hemolysis, excluding primary bone marrow failure or nutritional deficiencies as the primary cause 3.
Key laboratory findings supporting MAHA/TMA include:
- Schistocytes on peripheral smear - the hallmark finding that triggers immediate TMA evaluation 1
- Anemia (Hb 10.2 g/dL) with elevated reticulocyte count indicating hemolysis 4
- Normal ferritin (120) excluding iron deficiency 5
- Normal B12 (440) and folate (12) excluding megaloblastic anemia 5
- Normal MCV (90) making B12/folate deficiency unlikely despite the values 5
A critical pitfall: Do not dismiss TMA based on "rare" schistocytes alone, as low schistocyte counts can occur in early or evolving TMA, and the absence of abundant schistocytes does not exclude TMA due to low test sensitivity. 1
Immediate Diagnostic Workup Required
Order these tests urgently to determine the specific TMA subtype and guide treatment:
- ADAMTS13 activity level and inhibitor titer - distinguishes TTP (if <10%) from other TMAs 1
- Lactate dehydrogenase (LDH) - typically elevated in hemolysis 1, 4
- Haptoglobin - decreased in intravascular hemolysis 1, 4
- Direct antiglobulin test (DAT) - should be negative in MAHA, distinguishing from immune hemolysis 1, 4
- Platelet count - thrombocytopenia is part of the TMA triad 1
- Creatinine and urinalysis - assesses renal involvement (organ damage) 1
- Prothrombin time, PTT, fibrinogen - excludes DIC 1, 2
- Complement levels (C3, C4, CH50) - if atypical HUS suspected 1
Management Algorithm Based on ADAMTS13 Results
If ADAMTS13 Activity <10% (TTP):
Do not delay plasma exchange while awaiting ADAMTS13 results if TTP is strongly suspected clinically, as mortality increases with delayed treatment. 1
- Immediately initiate therapeutic plasma exchange (PEX) 1
- Administer methylprednisolone 1g IV daily for 3 days, with first dose given immediately after first plasma exchange 1
- Continue daily plasma exchange until platelet count exceeds 100-150 × 10⁹/L for 2 consecutive days 1
- Platelet transfusion is contraindicated unless life-threatening bleeding 1
If ADAMTS13 Activity >10% (Atypical HUS or Other TMA):
- Begin eculizumab therapy urgently (900 mg weekly for four doses, 1,200 mg week 5, then 1,200 mg every 2 weeks) 1
- Administer meningococcal vaccination and long-term penicillin prophylaxis 1
- Review all medications for potential TMA triggers and discontinue if possible 1
For Less Severe Cases (Grade 2):
- Administer prednisone 0.5-1 mg/kg/day 1
- Monitor hemoglobin levels weekly during steroid tapering 1
- Obtain hematology consultation 1
Transfusion Guidelines
- RBC transfusion only to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients 1
- Do not transfuse more than the minimum necessary 1
- Avoid platelet transfusion in TTP unless life-threatening bleeding 1
Monitoring During Acute Phase
- Daily CBC with differential, LDH, haptoglobin, and creatinine 1
- Regular platelet counts to evaluate response to therapy 1
- Blood pressure measurement and funduscopic examination to exclude malignant hypertension as a cause 1
Alternative Diagnoses to Consider
While MAHA/TMA is the primary diagnosis, evaluate for:
- Malignant hypertension - typically shows only moderate thrombocytopenia and fewer schistocytes, with normal or slightly reduced ADAMTS13 activity 1
- DIC - would show more pronounced coagulopathy with elevated fibrin degradation products 2
- Myelodysplastic syndrome - unlikely given elevated reticulocyte count and presence of schistocytes, but bone marrow examination may be needed if TMA workup is negative 5