Heparin-Induced Thrombocytopenia: Frequency and Pathogenesis

Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening prothrombotic, immune-mediated adverse drug effect that occurs with unfractionated heparin and to a lesser extent with low molecular weight heparin. HIT results from a platelet-activating immune response triggered by the interaction of heparin with a specific platelet protein, platelet factor 4 (PF4). When PF4 interacts with polyanions, both molecules form multimolecular complexes. The size of the resulting complexes depends on grade of sulfation and chain length of the polyanion. Large molecules such as unfractionated heparin form bigger complexes whereas shorter polyanions most likely form smaller complexes. HIT typically begins 4 to 14 days after starting heparin. Laboratory assays for diagnosing HIT antibodies are available. However, for interpretation of HIT-antibody tests it is important to consider that not all anti-PF4-heparin antibodies are pathogenic. The PF4-dependent enzyme-linked immunoassays (ELISA) are very sensitive for detecting all antibody classes to the PF4-heparin complexes, but are less specific than functional assays for detecting clinically-relevant anti-PF4-heparin antibodies. This review summarizes data on pathogenesis and frequencies of HIT in different patient population.