Standardization of Platelet Activation Tests for the Diagnosis of Heparin-Induced Thrombocytopenia: Communication from the ISTH-SSC Subcommittee on Immune-Mediated Platelet Disorders.

Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated adverse effect of heparin therapy, characterized by thrombocytopenia and a paradoxical increase in thrombotic risk. HIT results from platelet-activating immunoglobulin G antibodies targeting complexes of platelet factor (PF)4 and heparin, leading to FcγRIIA-mediated multicellular activation and a hypercoagulable state. Accurate diagnosis requires both immunological detection of antiplatelet factor 4/heparin antibodies and platelet activation confirmation of their potential pathogenicity. Immunoassays, while highly sensitive, lack clinical specificity due to their inability to distinguish between pathogenic and nonpathogenic antibodies. Platelet activation assays, although essential for definitive diagnosis, remain poorly standardized and are not widely available. This study addresses critical preanalytical and analytical variables influencing the accuracy of platelet activation HIT testing. It discusses key methodological considerations across various platelet activation assays, including the serotonin release assay, heparin-induced platelet activation, platelet aggregation tests, flow cytometry-based assays, and the heparin-induced multielectrode aggregometry method. Emphasis is placed on sample collection, donor selection, platelet preparation, heparin concentrations, and interpretation of results, including control strategies and troubleshooting indeterminate outcomes. The document also outlines assay-specific procedures and performance characteristics, highlighting the strengths and limitations of each method. By implementing standardized protocols and improving assay harmonization, diagnostic accuracy can be enhanced, ultimately improving clinical outcomes for suspected patients with HIT. This work reflects a collaborative expert consensus and aims to support laboratories in optimizing the application of platelet activation assays in HIT diagnostics.