Accuracy of the functional, flow cytometer-based Emo-Test HIT Confirm® for the diagnosis of heparin-induced thrombocytopenia

Abstract

Introduction: Rapid functional assays have been proposed to overcome the limitations of washed platelet assays in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT). Data on the diagnostic accuracy are, however, scarce and conflicting. We aimed to study the diagnostic accuracy of a rapid, flow cytometer-based assay and to explore sources of variability.

Material and methods: Frozen serum samples of 103 consecutive patients, evaluated for suspected HIT at our institution in 2017, and characterized with 4Ts score, IgG-PF4/heparin ELISA (GTI), HemosIL®Acustar (IgG), as well as heparin-induced platelet activation test (HIPA), were further tested using HIT Confirm, determining P-selectin release of donor platelets after incubation with patient's serum. The diagnosis of HIT was defined as a positive HIPA result.

Results: HIT was confirmed in 15 out of 103 patients corresponding to a prevalence of 14.6%. HIT Confirm was positive in 11 patients (10.7%), negative in 88 patients (85.4%), and inconclusive in 4 patients (3.9%). According to the intention-to-diagnose principle, the number of true positives was 9, the number of true negatives 83, the number of false negatives was 6, the number of false positives 5. This corresponds to a sensitivity of 60.0%, and a specificity of 94.3%. Modifications of the test did not improve sensitivity.

Conclusions: The rapid, flow cytometer-based assay HIT Confirm is able to verify HIT in positive patient samples but cannot rule-out HIT in clinical practice. Other rapid functional assays shall be studies in appropriately designed diagnostic accuracy studies.

Keywords: Flow cytometry/ methods; Heparin/ adverse effects; Thrombocytopenia/ chemically induced; Thrombocytopenia/ diagnosis.