A novel PF4-dependent platelet activation assay identifies patients likely to have heparin-induced thrombocytopenia/thrombosis (HIT).
Chest. 2016 Feb 18;
Authors: Padmanabhan A, Jones CG, Curtis BR, Bougie DW, Sullivan MJ, Peswani N, McFarland JG, Eastwood D, Wang D, Aster RH
BACKGROUND: Almost without exception, patients with heparin-induced thrombocytopenia/thrombosis (HIT) have antibodies that recognize platelet factor 4 (PF4) in a complex with heparin; however many heparin-treated patients without HIT are also antibody-positive. A platelet activation test, the serotonin release assay (SRA), is useful for identifying a subset of antibodies that are platelet-activating and most likely to cause HIT. However, this "gold standard" assay for HIT diagnosis is technically demanding and is routinely available only through referral laboratories, limiting its availability for timely diagnosis and management.
METHODS: We compared diagnostic performance of the SRA with that of a recently developed, technically simple platelet activation assay, the PF4-dependent p-selectin expression assay (PEA), which uses platelets pre-treated with PF4 as targets for antibody detection. Archived serum samples from 91 patients on whom clinical information (HIT "4Ts" score) was available were utilized. Patients with an Intermediate 4Ts score and a PF4 ELISA OD>2.0 or a High 4Ts score and a PF4 ELISA OD >1.0 were considered "HIT-positive"; others were designated "HIT-negative".
RESULTS: The PEA had higher diagnostic accuracy (Area under the Curve, 0.92 vs. 0.82; p=0.02) than the SRA using this definition of HIT. Eleven of 16 sera that were PEA+/SRA- were HIT-positive. Studies done with identical target platelets and serially-diluted HIT patient samples showed that the PEA is inherently more sensitive than the SRA for the detection of platelet-activating antibodies.
CONCLUSIONS: The PEA is technically less demanding than the SRA and may be more accurate for the diagnosis of HIT.
PMID: 26905366 [PubMed - as supplied by publisher]