What is the best course of action for a patient with severe thrombocytopenia, anemia, impaired renal function, and abnormal RBC morphology?

Urgent Hematology Consultation and Immediate TMA Workup Required

This patient requires immediate hematology consultation and urgent evaluation for thrombotic microangiopathy (TMA), given the constellation of severe thrombocytopenia (platelet count 17,000), anemia (hemoglobin 8.9), impaired renal function (creatinine 1.30, eGFR 45), and critically—the presence of schistocytes on peripheral smear. 1, 2, 3

Immediate Diagnostic Priorities

Critical Laboratory Tests to Order NOW

• ADAMTS13 activity level and inhibitor titer must be drawn immediately before any treatment is initiated, as this distinguishes TTP (ADAMTS13 <10%) from atypical HUS (ADAMTS13 >10%) 1, 3
• Lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, and direct antiglobulin test (DAT) to confirm hemolysis 1, 2, 3
• Reticulocyte count to assess bone marrow response to hemolysis 1, 2
• PT, aPTT, fibrinogen, and D-dimer to exclude disseminated intravascular coagulation (DIC) 1, 3
• Complement levels (C3, C4, CH50) to evaluate for complement-mediated atypical HUS 1, 3

Do NOT Delay Treatment While Awaiting ADAMTS13 Results

A critical pitfall is delaying plasma exchange while waiting for ADAMTS13 results if TTP is clinically suspected—mortality increases significantly with treatment delays. 2, 3 The triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction (renal impairment in this case) constitutes a medical emergency. 1, 3, 4

Interpretation of Current Laboratory Findings

Evidence Supporting TMA Diagnosis

• Schistocytes present on smear (even "trace/few" amounts are significant—low schistocyte counts can occur in early or evolving TMA, and test sensitivity is poor) 2, 3
• Severe thrombocytopenia (17,000) with critically low platelet count 1
• Normocytic anemia (MCV 77.4, hemoglobin 8.9) with evidence of RBC destruction 1, 3
• Marked RBC morphology abnormalities: burr cells (1+), ovalocytes (2+), elliptocytes (3+), anisocytosis (3+), and hypochromasia strongly suggest uremic changes from renal dysfunction 2, 5
• Renal impairment (creatinine 1.30, eGFR 45) is a cardinal feature of TMA 1, 2, 6
• Low anion gap (5) may reflect hypoalbuminemia from critical illness 1

Additional Uremic Features

The burr cells (echinocytes) and crenated RBCs are classic findings in uremia and chronic kidney disease, which this patient clearly has. 2, 5 However, the presence of schistocytes elevates this beyond simple uremic changes to concern for active TMA. 2, 3

Management Algorithm Based on TMA Grade

If ADAMTS13 <10% (TTP Confirmed)

Grade 4 TTP Management (Life-threatening): 1, 3

• Immediately initiate therapeutic plasma exchange (PEX) according to existing guidelines—do not delay 1, 3, 4
• Administer methylprednisolone 1g IV daily for 3 days, with first dose given immediately after first plasma exchange 1, 3
• Continue daily plasma exchange until platelet count exceeds 100-150 × 10⁹/L for 2 consecutive days 3
• Consider rituximab for refractory cases 3

If ADAMTS13 >10% (Atypical HUS or Other TMA)

Grade 3-4 Atypical HUS Management: 1, 3

• Begin eculizumab therapy urgently: 900 mg weekly for four doses, then 1,200 mg week 5, followed by 1,200 mg every 2 weeks 3
• Administer meningococcal vaccination and long-term penicillin prophylaxis (required with eculizumab) 3
• Review all medications for potential TMA triggers and discontinue if possible 3
• Supportive care with close monitoring of renal function 1, 6

Transfusion Management

Red Blood Cell Transfusion

At hemoglobin 8.9 g/dL, transfusion is NOT routinely indicated unless the patient is severely symptomatic or has acute coronary syndrome. 1, 3 The transfusion threshold is <7 g/dL for stable patients without cardiac disease. 1, 3 If transfusion is required:

• Transfuse only to relieve symptoms or achieve hemoglobin 7-8 g/dL 3
• Do not transfuse more than the minimum necessary 3

Platelet Transfusion

Platelet transfusion is generally contraindicated in TTP unless there is life-threatening bleeding (e.g., CNS hemorrhage), as it may worsen microvascular thrombosis. 1, 3 With a platelet count of 17,000, the bleeding risk is significant, but in the context of suspected TTP, hold platelet transfusion unless active life-threatening bleeding occurs. 1, 3

For non-TTP TMA (atypical HUS or other causes), platelet transfusion may be considered if platelet count remains <10,000 or if there is active bleeding. 1

Renal Function Considerations

Nephrology Consultation Required

The combination of renal impairment (eGFR 45) with TMA findings mandates nephrology involvement. 2 Specific evaluations needed:

• Urinalysis for proteinuria, hematuria, and cellular casts to distinguish glomerular from tubular disease 2
• Dysmorphic RBCs, proteinuria, or cellular casts indicate glomerular pathology 2
• Assess need for renal replacement therapy if acute kidney injury progresses 1, 4

Uremic Contribution to Hematologic Abnormalities

Chronic kidney disease contributes to anemia through decreased erythropoietin production and shortened RBC lifespan. 5, 7 However, do not attribute all findings to uremia alone—the presence of schistocytes and severe thrombocytopenia indicates active TMA requiring urgent intervention. 2, 3

Monitoring Plan During Acute Phase

• Daily CBC with differential, platelet count, LDH, haptoglobin, and creatinine 3
• Daily peripheral smear review to assess schistocyte burden 2, 3
• Neurologic examination at least twice daily (TTP commonly presents with neurologic symptoms) 3
• Strict intake/output monitoring and assessment for fluid overload 1

Critical Pitfalls to Avoid

1. Do not dismiss "trace" or "few" schistocytes as insignificant—early TMA can present with minimal fragmentation, and test sensitivity is poor 2, 3

2. Do not delay plasma exchange while awaiting ADAMTS13 results if clinical suspicion for TTP is high (triad of hemolytic anemia, thrombocytopenia, neurologic symptoms) 2, 3

3. Do not transfuse platelets in suspected TTP unless life-threatening bleeding occurs 1, 3

4. Do not assume findings are solely due to uremia—the combination of schistocytes, severe thrombocytopenia, and renal dysfunction requires TMA workup 2, 3

5. Do not order contrast imaging before calculating eGFR, as renal dysfunction increases risk with contrast studies 2

Additional Workup Based on TMA Evaluation Results

If TMA Workup is Negative

• Consider bone marrow examination if cytopenias persist without clear secondary cause, as myelodysplastic syndrome requires dysplasia in ≥10% of cells in at least one lineage 2
• Evaluate for malignancy as a cause of microangiopathic changes (though less likely given clinical presentation) 2
• Assess for medication-induced causes: chemotherapy, sirolimus, tacrolimus, quinine, certain antibiotics 1

Iron Studies and Nutritional Assessment

Given the microcytosis (MCV 77.4), hypochromasia, and elevated RDW (20.6), obtain complete iron studies (serum ferritin, transferrin saturation, TIBC) and vitamin B12/folate levels once the acute TMA evaluation is complete. 8 However, this is secondary to the urgent TMA workup and should not delay emergency management. 2, 3