Laboratory Methods for Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is associated with high morbidity and mortality. Because the pathophysiology of this complex disorder has remained unclear, so has the development of supportive diagnostic laboratory assays. The currently available laboratory methods for HIT include platelet-function assays such as the platelet aggregation assay, the serotonin release assay (SRA) and flow-cytometric assays, and antigen assays (enzyme-linked immunosorbent assays [ELISAs]) that quantitate the titer of anti-heparin-platelet factor 4 antibody. In a clinically defined HIT population, the aggregation and SRA are highly specific, but the aggregation is usually less sensitive than the SRA. The flow-cytometric assay has not been tested clinically, although it shows promising data. The ELISA has a higher sensitivity than the functional assays, but it gives a high frequency of false-positive results (e.g., patients with no clinical signs or symptoms of HIT, yet the ELISA titer is positive). False-negative results, in which patients are clinically HIT-positive yet have negative ELISA titers, are also observed. Positive aggregation and SRA results are generally associated with a higher antibody titer; however, a minimum critical titer is not identifiable. There is no direct correlation between the positive responses of any of these assays, and clinically positive patients can be missed by all assays. With these limitations, the combination of aggregation, SRA, and ELISA testing with multiple samples offers the best chance of identifying a positive HIT patient. Caution is advised for all assays, as none is optimal. The clinical impression remains the most important factor for the diagnosis of HIT.