The characteristics of the currently available platelet function assays (platelet aggregation, serotonin release, and flow cytometry) and enzyme-linked immunosorbent assays that quantitate antiheparin-platelet factor 4 antibody titers were studied using sera collected from clinically diagnosed heparin-induced thrombocytopenia patients, patients without heparin-induced thrombocytopenia, patients with platelet immune disorders other than heparin-induced thrombocytopenia, and normal individuals. The platelet aggregation assay was less sensitive than the serotonin release assay, which was less sensitive than the enzyme-linked immunosorbent assay (p < 0.001). Yet heparin-induced thrombocytopenia was identified by platelet aggregation assay in cases where the serotonin release assay and/or the enzyme-linked immunosorbent assay were negative. Patients with heparin-induced thrombocytopenia and thrombosis were more often positive than heparin-induced thrombocytopenia patients without thrombosis (p < 0.05). Positive platelet aggregation assay and serotonin release assay results were generally associated with a higher antibody titer; however, a minimum critical titer could not be identified. Over a 30-day period the percentage of positive responses did not change significantly even though clinical symptoms corrected in most heparin-induced thrombocytopenia patients. Multiple testing over several days enhanced the chance of detecting a positive, and combined results of the three assays further enhanced the positive response (p < 0.005). In patients without heparin-induced thrombocytopenia, false-positive results were obtained with the enzyme-linked immunosorbent assay. These data demonstrate that there is no direct correlation between the positive responses of these assays, that clinically positive patients can be missed by all assays, and the presence of antibody alone does not determine clinical heparin-induced thrombocytopenia. With these limitations, the combination of aggregation, serotonin release, and enzyme-linked immunosorbent assay testing with multiple samples offers the best chance of identifying a positive heparin-induced thrombocytopenia patient. Caution is advised for all assays as none is optimal.

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