What is the diagnosis for an elderly female patient with anemia and schistocytes on peripheral blood smear?

Diagnosis: Thrombotic Microangiopathy (TMA) - Most Likely Malignant Hypertension or Occult Malignancy

In an elderly female with hemoglobin 10.2 g/dL and schistocytes on peripheral smear, the diagnosis is microangiopathic hemolytic anemia (MAHA) with thrombotic microangiopathy (TMA), requiring urgent evaluation to distinguish between malignant hypertension, thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS), and occult malignancy. 1, 2

Immediate Diagnostic Workup

Order these tests urgently before any treatment:

• ADAMTS13 activity level and inhibitor titer - this is the single most critical test to differentiate TTP from other causes 1
• Complete blood count with platelet count 1
• Lactate dehydrogenase (LDH) and haptoglobin 1, 2
• Direct antiglobulin test (Coombs) - must be negative to confirm MAHA 2
• Peripheral blood smear review for schistocyte quantification 1
• Creatinine and urinalysis for hematuria/proteinuria 1
• Blood pressure measurement and funduscopic examination 3
• Prothrombin time, PTT, and fibrinogen to exclude DIC 1

Differential Diagnosis Framework

The triad defining TMA consists of non-immune microangiopathic hemolysis, thrombocytopenia, and organ involvement (typically renal). 1 However, up to 50% of cases at onset do not show all three features clearly. 2

Primary Considerations Based on Clinical Context:

1. Malignant Hypertension (Most Common in Elderly)

• TMA associated with malignant hypertension typically shows only moderate thrombocytopenia and few schistocytes compared to TTP/HUS 3
• Look for severe blood pressure elevation with advanced retinopathy on funduscopic exam 3
• ADAMTS13 activity will be normal or only slightly reduced (not <10%) 3
• Blood pressure lowering will improve TMA within 24-48 hours 3

2. Thrombotic Thrombocytopenic Purpura (TTP)

• Diagnosed if ADAMTS13 activity <10% 1
• More severe thrombocytopenia and abundant schistocytes than malignant hypertension 3
• Neurological symptoms common 3

3. Atypical Hemolytic Uremic Syndrome (aHUS)

• Diagnosed if ADAMTS13 activity >10% with clinical TMA 1
• Predominantly renal involvement 1

4. Occult Malignancy

• Gastric, breast, prostate, lung cancers and lymphoma commonly associated with MAHA 4
• Colon signet-ring cell carcinoma can present with MAHA as initial manifestation 4
• Consider age-appropriate cancer screening in elderly patients 4

Critical Pitfalls to Avoid

Do not dismiss the diagnosis based on "rare" or "few" schistocytes alone - 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 Malignant hypertension characteristically shows fewer schistocytes than TTP. 3

Do not delay plasma exchange while awaiting ADAMTS13 results if TTP is strongly suspected clinically - mortality increases with delayed treatment. 1 However, given the moderate anemia (Hgb 10.2) and elderly age, malignant hypertension or malignancy-associated MAHA may be more likely than acute TTP.

Do not assume all three features (anemia, thrombocytopenia, organ dysfunction) must be present - initial presentation may be incomplete. 2

Management Algorithm

If Blood Pressure Severely Elevated with Retinopathy:

• Initiate controlled blood pressure lowering 3
• Monitor for TMA improvement within 24-48 hours 3
• This suggests malignant hypertension as the cause 3

If ADAMTS13 <10% (Confirms TTP):

• Immediately initiate therapeutic plasma exchange 1
• Administer methylprednisolone 1g IV daily for 3 days 1
• Platelet transfusion is contraindicated unless life-threatening bleeding 1

If ADAMTS13 >10% with Clinical TMA (Suggests aHUS):

• Begin eculizumab therapy 1
• Administer meningococcal vaccination and long-term penicillin prophylaxis 1

If No Clear Cause Identified:

• Screen for occult malignancy with age-appropriate studies including colonoscopy, CT chest/abdomen/pelvis, and mammography 4
• Consider hematology consultation 1

Transfusion Guidelines

RBC transfusion should only be done to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients. 1 Given the current Hgb of 10.2 g/dL, transfusion is likely not indicated unless symptomatic. 1

Platelet transfusion is generally contraindicated in TTP unless life-threatening bleeding. 1

Monitoring During Acute Phase

• Daily CBC with differential, LDH, haptoglobin, and creatinine 1
• Serial blood pressure measurements if malignant hypertension suspected 3
• Platelet count monitoring to assess response to therapy 1