What antibodies should be ordered to rule out heparin-induced thrombocytopenia (HIT)?

Antibody Testing for Heparin-Induced Thrombocytopenia

For patients with suspected heparin-induced thrombocytopenia (HIT), anti-PF4 antibody testing should be ordered as the first-line test, specifically using an IgG-specific ELISA assay due to its superior specificity while maintaining excellent sensitivity. 1

Diagnostic Algorithm for HIT

Step 1: Clinical Assessment

• Calculate the 4T score to determine pre-test probability of HIT 1, 2
• For intermediate (4-5) or high (6-8) probability scores, proceed with laboratory testing 1, 2
• In post-cardiac surgery patients, analyze the platelet count evolution profile instead of the 4T score, with a "biphasic" pattern strongly suggesting HIT 1

Step 2: Initial Laboratory Testing

• Order anti-PF4 antibody testing using an IgG-specific ELISA assay 1, 3
• IgG-specific assays provide better diagnostic information than polyspecific assays (IgG/A/M) with improved specificity 3, 4
• The negative predictive value of anti-PF4 ELISA is excellent (nearly 100%), effectively ruling out HIT if negative 1

Step 3: Interpretation of Results

• A negative anti-PF4 antibody test effectively rules out HIT due to its high sensitivity and negative predictive value 1, 5
• For positive anti-PF4 antibody results, consider the optical density (OD) value - higher values correlate with increased likelihood of true HIT 4, 6
• Note that anti-PF4 antibodies can appear without clinical HIT, particularly after cardiac surgery 1

Step 4: Confirmatory Testing

• If anti-PF4 antibody test is positive with intermediate or high clinical probability, order a functional assay for confirmation 1
• The serotonin release assay (SRA) is considered the gold standard functional test 1, 5
• Alternative functional tests include heparin-induced platelet activation (HIPA) test 1

Important Considerations

• Immunological tests (ELISA) should be performed as soon as possible to quickly rule out HIT and guide investigation toward other causes of thrombocytopenia 1
• While polyspecific assays (detecting IgG/A/M) have excellent sensitivity, they have lower specificity and can lead to overdiagnosis of HIT 3, 7
• IgG-specific assays are preferred as IgM and IgA antibodies alone are rarely associated with clinical HIT 3, 7
• The optical density value in ELISA testing correlates with the probability of having true HIT - higher values increase positive predictive value 4, 6

Common Pitfalls and Caveats

• Avoid ordering anti-PF4 antibody testing in patients with low clinical probability (4T score ≤3), as this leads to unnecessary testing and potential overdiagnosis 1, 8
• Do not delay discontinuation of heparin and initiation of alternative anticoagulation while waiting for laboratory results in patients with high clinical probability 2
• Be aware that functional tests (SRA, HIPA) are technically difficult, require specialized laboratories, and may not be readily available at all institutions 1, 5
• Remember that a positive anti-PF4 antibody test alone is insufficient for diagnosis, as these antibodies can appear without clinical HIT, particularly after cardiac surgery 1