Implementation of Whole-Blood Impedance Aggregometry for Heparin-Induced Thrombocytopenia Functional Assay and Case Discussion

Jing Jin, CLS; Steven Andrew Baker, MD, PhD; Evan T. Hall, MD; Saurabh Gombar, MD, PhD; Adelaide Bao; James L. Zehnder, MD


Am J Clin Pathol. 2019;152(1):50-58. 

In This Article

Abstract and Introduction


Objectives: The diagnosis of heparin-induced thrombocytopenia (HIT) ideally requires a functional assay to confirm. 14C-serotonin release assay (SRA) as "gold standard" is technically challenging and unsuitable for routine use. We conducted a study to assess the performance of whole-blood impedance aggregometry (WBIA) as a simple and rapid HIT functional assay.

Methods: Platelet factor 4 (PF4)/immunoglobulin G (IgG) antibody, WBIA, and SRA were tested on 70 patients suspected of having HIT. Patients with a 4Ts score of 4 or more, positive PF4/IgG, and positive SRA were considered HIT positive; others were designated HIT negative.

Results: WBIA had 85.7% (6/7) sensitivity and 98.4% (61/62) specificity, which were not statistically different compared with SRA. Sixty-two of 70 patients had concordant results (five positive and 57 negative) by both WBIA and SRA. Eight discordant cases revealed the importance of recognizing donor effect, interferences, and the presence of heparin-independent or non-heparin-dependent antibodies in functional assays.

Conclusions: Implementation of WBIA could facilitate timely diagnosis and management of HIT.


Heparin-induced thrombocytopenia (HIT) is an immune-mediated immunoglobulin G (IgG) response to platelet factor 4 (PF4)—heparin complexes occurring in approximately 1% of patients exposed to unfractionated heparin.[1] HIT remains an important cause of in-hospital morbidity and mortality and is associated with substantially higher cost.[2] Thus, prevention and early diagnosis of HIT are key to minimizing morbidity, mortality, and costs associated with heparin use. HIT is a clinicopathologic diagnosis ideally combining pretest probability assessment with rapid and accurate confirmatory testing. Immunologic methods for detection of PF4 antibodies are widely available but are associated with low specificity, limiting their utility. Based on the work of Sheridan et al[3] and Warkentin,[4] the gold-standard functional assay for HIT is the serotonin release method. However, because of the complexity of the method and use of radiolabeled 14C, this test is limited to a few large regional reference laboratories in North America.

Whole-blood impedance aggregometry (WBIA) has been proposed as a rapid and simple alternative to 14C-serotonin release assay (SRA).[5,6] We sought to prospectively determine the utility of this assay in HIT diagnosis using a combination of pretest probability, PF4/IgG enzyme immunosorbent assay (ELISA), WBIA, and SRA in a tertiary referral hospital setting.