Laboratory diagnosis of heparin-induced thrombocytopenia

The characteristics of the currently available platelet function assays (pl atelet aggregation, serotonin release, and flow cytometry) and enzyme-linke d immunosorbent assays that quantitate antiheparin-platelet factor 4 antibo dy titers were studied using sera collected from clinically diagnosed hepar in-induced thrombocytopenia patients, patients without heparin-induced thro mbocytopenia, patients with platelet immune disorders other than heparin-in duced thrombocytopenia, and normal individuals. The platelet aggregation as say was less sensitive than the serotonin release assay, which was less sen sitive than the enzyme-linked immunosorbent assay (p < 0.001). Yet heparin- induced thrombocytopenia was identified by platelet aggregation assay in ca ses where the serotonin release assay and/or the enzyme-linked immunosorben t assay were negative. Patients with heparin-induced thrombocytopenia and t hrombosis were more often positive than heparin-induced thrombocytopenia pa tients without thrombosis (p < 0.05). Positive platelet aggregation assay a nd 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 si gnificantly 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 f urther enhanced the positive response (p < 0.005). In patients without hepa rin-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 cl inically positive patients can be missed by all assays, and the presence of antibody alone does not determine clinical heparin-induced thrombocytopeni a. With these limitations, the combination of aggregation, serotonin releas e, and enzyme-linked immunosorbent assay testing with multiple samples offe rs the best chance of identifying a positive heparin-induced thrombocytopen ia patient. Caution is advised for all assays as none is optimal.