symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. Mechanism The administration of heparin can cause the development of HIT antibodies, suggesting heparin may act as a hapten, thus may be targeted by the immune system. In HIT, the immune system forms antibodies against heparin when it is bound to a protein called platelet factor 4 (PF4). These antibodies are usually of the IgG class and their development usually takes about 5 days. However, those who have been exposed to heparin in the last few months may still have circulating IgG, as IgG-type antibodies generally continue to be produced even when their precipitant has been removed. This is similar to immunity against certain microorganisms, with the difference that the HIT antibody does not persist more than three months. HIT antibodies have been found in individuals with thrombocytopenia and thrombosis who had no prior exposure to heparin, but the majority are found in people who are receiving heparin. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. In addition, the reticuloendothelial system (mostly the spleen) removes the antibody-coated platelets, further contributing to the thrombocytopenia. Formation of PF4-heparin antibodies is common in people receiving heparin, but only a proportion of these develop thrombocytopenia or thrombosis. This has been referred to as an "iceberg phenomenon". Diagnosis HIT may be suspected if blood tests show a falling platelet count in someone receiving heparin, even if the heparin has already been discontinued. Professional guidelines recommend that people receiving heparin have a complete blood count (which includes a platelet count) on a regular basis while receiving heparin. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood