What is the most likely diagnosis for a patient with anemia, schistocytes on peripheral blood smear, and lab results showing low hemoglobin, normal mean corpuscular volume (MCV), elevated ferritin, normal vitamin B12, and normal folate levels?

Microangiopathic Hemolytic Anemia (MAHA) with Thrombotic Microangiopathy (TMA)

The most likely diagnosis is thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), given the presence of schistocytes on peripheral smear combined with anemia and an elevated reticulocyte index indicating hemolysis. 1

Diagnostic Rationale

The clinical picture demonstrates the classic triad defining TMA: non-immune microangiopathic hemolysis, thrombocytopenia (implied by schistocytes), and organ involvement 1. The key diagnostic features include:

• Schistocytes on peripheral smear are the hallmark finding of microangiopathic hemolytic anemia and indicate endothelial injury with red blood cell fragmentation 1, 2
• Reticulocyte index of 1.3 suggests an appropriate bone marrow response to hemolysis, distinguishing this from hypoproliferative anemias 3
• Normal MCV (90) with anemia points toward a normocytic process consistent with hemolysis rather than nutritional deficiencies 3
• Normal ferritin (120), B12 (440), and folate (12) effectively exclude iron deficiency anemia, pernicious anemia, and megaloblastic causes 1

Critical Immediate Actions Required

Order ADAMTS13 activity level and inhibitor titer immediately before any treatment decisions, as this distinguishes TTP (ADAMTS13 <10%) from atypical HUS (ADAMTS13 >10%) 1. Additional urgent laboratory tests include:

• Complete blood count with platelet count to assess thrombocytopenia severity 1
• Lactate dehydrogenase (LDH) and haptoglobin to confirm hemolysis 1
• Direct antiglobulin test (DAT) to exclude immune-mediated hemolysis 1
• Creatinine and urinalysis for hematuria/proteinuria to assess renal involvement 1
• Prothrombin time, activated partial thromboplastin time, and fibrinogen to exclude disseminated intravascular coagulation 1

Management Algorithm Based on ADAMTS13 Results

If ADAMTS13 Activity <10% (TTP):

Immediately initiate therapeutic plasma exchange without waiting for confirmatory results if TTP is strongly suspected clinically, as mortality increases with delayed treatment 1. Concurrent therapy includes:

• 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
• Avoid platelet transfusion unless life-threatening bleeding occurs, as it is generally contraindicated in TTP 1

If ADAMTS13 Activity >10% (Atypical HUS):

• 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 initiate long-term penicillin prophylaxis 1
• Test complement levels (C3, C4, CH50) to confirm complement-mediated atypical HUS 1

Important Differential Considerations

While TMA is most likely, consider these alternative diagnoses if initial workup is negative:

• Malignancy-associated MAHA: Gastric, breast, prostate, lung cancers, and lymphoma can present with schistocytes 4. However, the normal ferritin and lack of other systemic symptoms make this less likely 1
• Vitamin B12 deficiency ("pseudo-TMA"): Can rarely present with schistocytes, hemolysis, and thrombocytopenia 5, 6. However, the normal B12 level (440) and normal MCV (90) make this diagnosis unlikely 1
• Myelodysplastic syndrome: Unlikely given the elevated reticulocyte count and presence of schistocytes, but bone marrow examination may be needed if TMA workup is negative 1

Critical Pitfalls to Avoid

Do not delay plasma exchange while awaiting ADAMTS13 results if clinical suspicion for TTP is high 1. The presence of schistocytes with hemolysis constitutes a medical emergency requiring immediate intervention.

Do not dismiss the diagnosis based on "rare" or few 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, 7.

Transfusion Guidelines

• RBC transfusion should only be administered to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients 1
• Transfuse only the minimum necessary volume 1

Monitoring During Acute Phase

Monitor daily: complete blood count with differential, LDH, haptoglobin, and creatinine 1. Reassess clinical status and laboratory parameters to guide continuation or modification of therapy.