HIT Antibodies w/Reflex to Serotonin Release Assay (SRA) (LAB29247)

HIT testing should only be pursued on patients with a 4T score of 4 or greater.


Clinical Background

Heparin-induced thrombocytopenia (HIT) is a rare but serious adverse reaction to heparin therapy that results in a drop in platelets and an increased risk for thrombosis. The pathophysiology is driven by circulating antibodies to platelet factor 4 which, in the presence of heparin, leads to the indiscriminate activation of platelets. Diagnosis at BJH involves a screening latex immunoassay (LIA) to detect these antibodies, followed by a reflex to the highly specific serotonin release assay (SRA).

A clinical scoring tool, the 4T score, is endorsed by the American Society of Hematology to identify patients for whom testing is indicated. A 4T score of less than 4 has a very high negative predictive value, effectively ruling out HIT in the majority of patients. However, these guidelines also recommend complete cessation of heparin products and initiation of an alternative anticoagulant when deciding to test for HIT. Heparin offers many advantages over these alternatives, complicating the management of these patients in the period between LIA and SRA results.

Compounding the issue is the imperfect specificity of the LIA screening test. Positive results on patients with a low pre-test probability often fail to confirm the diagnosis by SRA. By reserving testing for those at particularly increased risk of thrombotic complications of HIT, providers can provide more optimal anticoagulation to their patients.

Common Pitfalls
  • Performing the anti-PF4 immunoassay in patients with a 4T score <4 leads to false-positive results with significant downstream consequences.
Key Takeaways
  • Only order HIT testing for patients in whom the pre-test probability is high, as estimated by the 4T score or other similar predictors.
References
  1. Cuker et al; American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018; 2 (22): 3360–3392. doi: https://doi.org/10.1182/bloodadvances.2018024489.

Aliases: Anti-Platelet Factor 4 (PF4), Serotonin Release Assay (SRA), P-selectin expression assay (PEA)


Written by: Nicholas Spies, MD

Reviewed by: Nathan McLamb, MD

Last Edited: 2023-07-08

Last Reviewed: 2023-07-12