A critical evaluation of assays for detecting antibodies to the heparin-PF4 complex

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic complication of heparin therapy. The syndrome is the result of the production of an antibody to the complex that forms between heparin and platelet factor 4 (H-PF4) released from activated platelets. IgG antibodies bind to platelet Fc receptors and cause platelet activation, resulting in thrombocytopenia and greatly increased risk of thrombosis. Tests for the H-PF4 antibody can be classified into functional assays (which rely on the demonstration of platelet activation) and immunoassays (which detect the presence of an antibody without regard for its functional ability). The functional assays have a greater specificity for clinical HIT, but require normal donor platelets and are relatively unstandardized. The immunoassays have the advantage of better standardization and do not require normal platelets, but may give positive results in the absence of clinical HIT. The choice of test is usually dictated by what is possible for a given laboratory in terms of instrumentation, expertise, and interest. For most institutions this will be a commercially available enzyme-linked immunosorbent assay. Although HIT is a true clinicopathological syndrome, there are several reasons why its diagnosis still rests primarily on clinical grounds. First, laboratory tests may not be available locally. Second, they may not be available in a sufficiently timely manner. Finally, available tests are not completely sensitive or specific for the condition. There is, therefore, a continuing need to develop more rapid testing strategies with greater specificity for clinical HIT.