Heparin-induced thrombocytopenia

and Objectives. There are two types of heparin-induced thrombocytopenia (HI T). HIT I is characterized by a transitory, slight and asymptomatic-reducti on in platelet count, occurring in the first 1-2 days of therapy, that reso lves spontaneously; in contrast, HIT II, which has an immunologic origin, i s characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withd rawal. HIT II is the most frequent and danger of heparin therapy; in fact, in spite of it can be complicated by venous and arterial thrombosis. Theref ore, the recognition of CHIT II may be difficult due to the underlying thro mbotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical gui delines for the clinical diagnosis and treatment of HIT II. State of the Art. The prevalence of HIT II, as confirmed by laboratory test s, seems to be about 2% in receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The i mmunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-hep arin/PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-he parin/PF4 immunocomplex activates platelets mainly through binding with the Fc gamma RIIa (CD32) receptor. The onset of thrombocytopenia is independen t of the dosage, schedule and route of administration of heparin. Orthopedi c and cardiovascular surgery patients receiving post-surgical prophylaxis o r treatment for deep venous thrombosis are at higher risk of HIT II. Beside s thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses wh ich carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-depend ent anti bodies. Functional tests, such as platelet aggregation and C-14-se rotonin release assay and immunologic tests, such as the search for anti-PF 4/heparin complex antibodies by an ELISA method are available. If HITT II i s probable, heparin must be immediately suspended and an alternative antico agulant therapy should be initiated before resolution of thrombocytopenia a nd the following treatment with a vitamin K antagonist. The general opinion Is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direc t thrombin inhibitors such as hirudin. Perspectives. Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors tha t induce the occurrence of thrombotic complications. The best therapeutic s trategy remains to be confirmed in larger clinical trials. (C)2000, Ferrata Storti Foundation.