Thrombocytopenia is a well-recognized complication of heparin therapy, usually occurring within the first 10 days after heparin treatment has started . There are two forms of heparin-induced thrombocytopenia (HIT) (table 1):
- The most common form of thrombocytopenia, of no clinical consequence (type I heparin-induced thrombocytopenia), is typically characterized by a slight fall in platelet count that occurs within the first two days after heparin initiation and often returns to normal with continued heparin administration . The mechanism of the thrombocytopenia is nonimmune and appears to be due to a direct effect of heparin on platelet activation [3,4].
- The less common and more serious form (heparin-induced thrombocytopenia, type II; HIT-II) is an immune-mediated disorder characterized by the formation of antibodies against the heparin-platelet factor 4 complex. This disorder has also been called heparin-associated immune thrombocytopenia, heparin-associated thrombocytopenia and thrombosis (HITT), and white clot syndrome [2,5]. White clot syndrome refers to platelet-rich arterial thrombosis (rather than fibrin-rich venous thrombosis), which occurs with high frequency in patients who develop this disorder .
For the remainder of this review, the term HIT will refer only to the immune form (ie, type II). The clinical manifestations, diagnosis, prevention, and treatment of HIT will be reviewed here [2,6-10]. The clinical use of heparin and low molecular weight heparin is discussed separately. (See "Therapeutic use of heparin and low molecular weight heparin".)
INCIDENCE AND RISK FACTORS
A critical assessment of immune-mediated HIT suggests a frequency of 0.2 to 5.0 percent in patients exposed to heparin for more than four days [11-16], with an overall incidence of 2.6 percent noted in a meta-analysis . The incidence is closer to 0.2 percent for those treated with unfractionated heparin (UFH) for less than four days [17,18].
Of importance, two prospective observational studies showed a surprisingly high incidence of thrombocytopenia in patients treated with either unfractionated or low molecular weight heparin for ≥4 days, with 15 percent of patients showing a >50 percent reduction in baseline platelet counts in one study  and 42 percent in the other .