Pathophysiology and laboratory testing of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) type II is an immune-mediated reaction that generally occurs 5 to 14 days after initiation of heparin therapy. It is characterized by a severe decline in platelet count (by >50%) in association with a new thromboembolic complication. Type II HIT is mediated by antibodies, usually of the IgG class. The antibodies cause platelet activation in the presence of heparin or other polysulfated saccharides. The antigen in type II HIT frequently is a complex of platelet factor 4 (PF4) and heparin. In addition to stimulating platelet activation, type II HIT antibodies bind to PF4/heparin complexes on the surface of endothelial cells, leading to activation of the cells. Concomitant activation of platelets and endothelial cells together with enhanced thrombin generation are likely causes for the thromboembolic events. The percentage of patients receiving heparin who develop type II HIT antibodies is higher than the percentage of patients who develop clinical symptoms characteristic of type II HIT. Therefore, it is currently not indicated to screen asymptomatic patients for the development of HIT antibodies. If clinical symptoms of HIT appear, the clinical diagnosis should be confirmed, when possible, by a laboratory test for HIT antibodies. Assays for detection of HIT antibodies are either functional assays, which measure heparin-dependent platelet activation, or antigen assays based on the enzyme-linked immunosorbent assay (ELISA) technique. A reasonable approach to applying these laboratory tests is to use one assay technique as a screening test and reserve the other for testing samples that had negative screening results when the diagnosis of HIT is strongly suspected.
Chong
B H
BH
Department of Hematology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Eisbacher
M
M
D019411:Clinical Laboratory Techniques; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology
D010978:Platelet Factor 4; D006493:Heparin