What tests should be ordered for a 66-year-old man with abdominal pain, distention, and an enlarged liver, who has a platelet count of 680,000, and is being treated with low molecular weight heparin (LMWH) for suspected thrombosis?

Testing for Suspected Heparin-Induced Thrombocytopenia in a Patient with Thrombosis and Thrombocytosis

Testing for anti-PF4 antibodies should be ordered immediately for this patient with thrombosis and elevated platelet count on LMWH therapy, as this represents a possible atypical presentation of heparin-induced thrombocytopenia (HIT). 1

Clinical Assessment

This 66-year-old man presents with several concerning features:

• Abdominal pain and distention
• Enlarged liver
• Thrombocytosis (platelet count 680,000, persistently elevated at 600,000)
• Confirmed thrombosis on Doppler ultrasound
• Currently receiving LMWH

While classic HIT typically presents with thrombocytopenia, this patient's presentation raises concern for an atypical manifestation of HIT or another thrombotic disorder.

Diagnostic Algorithm

Step 1: Assess Clinical Probability of HIT

• Apply the 4T score to stratify risk 1:
  • Thrombocytopenia: 0 points (patient has thrombocytosis, not thrombocytopenia)
  • Timing: Unclear from information provided
  • Thrombosis: 2 points (confirmed thrombosis)
  • Other causes: Need to evaluate

Even with an atypical presentation (thrombocytosis rather than thrombocytopenia), the presence of thrombosis in a patient receiving heparin warrants investigation.

Step 2: Order Appropriate Laboratory Tests

1. Anti-PF4 antibody testing (immunological assay) 1

   • This is the first-line test for suspected HIT
   • High sensitivity allows rapid exclusion of HIT if negative

2. Peripheral blood smear examination 1

   • Essential to evaluate for:
     • Platelet clumping/aggregates
     • Morphological abnormalities
     • Evidence of other hematologic disorders

3. Basic coagulation studies 1

   • PT, aPTT, fibrinogen, D-dimers
   • To assess for DIC or other coagulopathies

4. If anti-PF4 antibodies are positive, order:

   • Functional platelet activation assay (serotonin release assay or heparin-induced platelet activation test) 1
   • These tests have higher specificity for clinically significant HIT

Important Considerations

Atypical Presentations of HIT

• While HIT classically presents with thrombocytopenia, cases with normal or elevated platelet counts have been reported 2
• The diagnosis should not be excluded based solely on the absence of thrombocytopenia, especially when thrombosis is present

Risk of Delayed Diagnosis

• Failure to diagnose HIT can lead to catastrophic thrombotic complications
• If clinical suspicion is high, anti-PF4 testing should be performed regardless of platelet count 1

Alternative Diagnoses to Consider

• Myeloproliferative neoplasm (given the marked thrombocytosis)
• Antiphospholipid syndrome 1
• Cancer-associated thrombosis with reactive thrombocytosis
• Thrombotic thrombocytopenic purpura

Management Implications

If HIT is suspected:

• Discontinue all heparin products immediately (including LMWH)
• Initiate alternative non-heparin anticoagulation (argatroban, bivalirudin, danaparoid, or fondaparinux) 1
• Do not start warfarin until platelet count has normalized, as this can precipitate venous limb gangrene or skin necrosis 3

Common Pitfalls to Avoid

1. Failing to consider HIT in patients without thrombocytopenia
2. Delaying anti-PF4 antibody testing while waiting for platelet count to decrease
3. Continuing heparin while awaiting test results in a patient with high clinical suspicion
4. Starting warfarin before adequate alternative anticoagulation and platelet count recovery

The combination of thrombosis and markedly elevated platelets in this patient receiving LMWH requires prompt investigation with anti-PF4 antibody testing and peripheral blood smear examination to guide appropriate management.