Fcγ RII a proteolysis as a diagnostic biomarker for heparin‐induced thrombocytopenia

Summary Background A significant challenge in the management of heparin‐induced thrombocytopenia ( HIT ) patients is making a timely and accurate diagnosis. The readily available enzyme immunoassays ( EIA s) have low specificities. In contrast, platelet activation assays have higher specificities, but they are technically demanding and not widely available. In addition, ~ 10% of samples referred for HIT testing are initially classified as indeterminate by the serotonin release assay ( SRA ), which further delays accurate diagnosis. HIT is characterized by platelet activation, which leads to F cγ RII a proteolysis. This raises the possibility that identification of the proteolytic fragment of F cγ RII a could serve as a surrogate marker for HIT . Objectives To determine the specificity of platelet F cγ RII a proteolysis induced by sera from patients with HIT , and to correlate the results with those of the SRA . Methods/Patients Sera from HIT patients and control patients with other thrombocytopenic/prothrombotic disorders were tested for their ability to proteolyse F cγ RII a. The results were correlated with anti‐platelet factor 4 ( PF 4)/heparin antibodies ( EIA ), and heparin‐dependent platelet activation ( SRA ). Results Only HIT patient samples (20/20) caused heparin‐dependent Fcγ RII a proteolysis, similar to what was shown by the SRA . None of the samples from the other patient groups or hospital controls caused Fcγ RII a proteolysis. Among nine additional samples that tested indeterminate in the SRA , F cγ RII a proteolysis resolved five samples that had a positive anti‐ PF 4/heparin EIA result; three had no F cγ RII a proteolysis, and two were shown to have heparin‐dependent F cγ RII a proteolysis Conclusions This study suggests that heparin‐dependent F cγ RII a proteolysis is at least as specific as the SRA for the diagnosis of HIT .