What do I need to order if I'm suspicious of heparin-induced thrombocytopenia (HIT)?

Diagnostic Workup for Suspected Heparin-Induced Thrombocytopenia (HIT)

When you suspect HIT, immediately calculate the 4T score and order anti-PF4 antibody testing (immunoassay/ELISA), while simultaneously stopping all heparin and starting therapeutic-dose alternative anticoagulation without waiting for laboratory results if the 4T score is intermediate (4-5) or high (≥6). 1, 2

Immediate Clinical Assessment

Calculate the 4T Score first to determine pre-test probability:

• Low probability (≤3 points): HIT is excluded; continue heparin and investigate other causes of thrombocytopenia 1, 2
• Intermediate probability (4-5 points): Stop all heparin immediately, order anti-PF4 antibodies, and start therapeutic-dose alternative anticoagulation 1, 2
• High probability (≥6 points): Stop all heparin immediately, order anti-PF4 antibodies, start therapeutic-dose alternative anticoagulation, and do not wait for lab confirmation 1, 2

The 4T score evaluates: magnitude of platelet count fall, timing of thrombocytopenia relative to heparin exposure, presence of thrombosis, and likelihood of other causes 3, 4

Laboratory Testing Algorithm

First-Line Test: Anti-PF4 Antibody Immunoassay (ELISA)

Order anti-PF4 antibody testing immediately as your initial laboratory test 1, 5:

• This detects antibodies against the heparin-platelet factor 4 complex 5, 6
• Results are typically available within 24-48 hours 5
• If negative with intermediate 4T score: HIT is excluded; you can resume heparin with close platelet monitoring 1
• If positive with intermediate or high 4T score: Proceed to functional testing for confirmation 1

Confirmatory Test: Functional Platelet Activation Assay

If anti-PF4 antibodies are positive, order a functional test to confirm the diagnosis 1:

• Serotonin Release Assay (SRA): Considered the gold standard with near 100% specificity 1, 5
• Heparin-Induced Platelet Activation (HIPA) test: Alternative functional assay 1
• These tests demonstrate that the patient's antibodies actually activate platelets in the presence of heparin 5, 6
• Positive functional test confirms HIT diagnosis 1

Critical caveat: Functional tests take several days and are only available in specialized laboratories, so never delay treatment while waiting for these results 1, 5

Additional Laboratory Monitoring

Order baseline coagulation studies before starting alternative anticoagulation 1:

• Baseline aPTT: Required before starting argatroban or bivalirudin, as you'll need to monitor aPTT at 1.5-3 times baseline 1, 7
• Baseline INR: Needed if transitioning to warfarin later 1
• Complete blood count: Document baseline platelet count and monitor every 2-3 days until recovery 1

Common Pitfalls to Avoid

Do not wait for laboratory confirmation before acting if clinical suspicion is intermediate or high—the thrombotic risk is too great 2, 4:

• Thrombosis occurs in 30-50% of HIT patients, with an odds ratio of 37 for developing new clots 4
• The median platelet nadir is 50-60 × 10⁹/L, but severe thrombocytopenia can occur 8

Do not order only the immunoassay and stop there if it's positive with intermediate probability 1:

• Anti-PF4 antibodies occur more frequently than actual HIT disease 4
• Functional testing distinguishes clinically significant antibodies from benign ones 1, 5

Do not forget to check for all sources of heparin exposure 2:

• Stop heparin flushes in IV lines 2
• Remove heparin-coated catheters 2
• Discontinue subcutaneous heparin prophylaxis 1
• Check for heparin in dialysis circuits 5

Do not order platelet transfusions unless there is active life-threatening bleeding or a high-risk invasive procedure 1:

• Platelet transfusions may paradoxically worsen thrombosis in HIT 1, 2

Timing Considerations

Recognize the typical timing patterns to strengthen your clinical suspicion 3, 8:

• Typical HIT: Platelet count drops 5-14 days after starting heparin 4, 8
• Rapid-onset HIT: Platelet drop within 24 hours if heparin exposure in the past 3 months (preformed antibodies) 8
• Delayed HIT: Can occur days to weeks after heparin discontinuation 8

Monitor platelet counts every 2-3 days from day 4 to day 14 in patients receiving heparin with >1% HIT risk 1