Platelet aggregation studies for the diagnosis of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious clinical disorder characterized by the sudden onset of thrombocytopenia and is often associated with paradoxic thrombosis in patients receiving heparin. The diagnosis of HIT has been hampered by problems with the laboratory methods used to establish the diagnosis. The authors evaluated the role of the source of heparin and donor platelets on the results of an ex vivo platelet aggregation assay for the diagnosis of HIT. Bovine lung and porcine mucosal heparins were equally effective at mediating ex vivo platelet aggregation induced by 17 of 17 known HIT-positive plasma samples. Plasma from 11 patients with a history of thrombocytopenia, exposure to heparin, and previously negative aggregation assays remained negative with both heparins on repeat testing. High concentrations of either heparin inhibited the aggregation response of normal platelets to HIT-positive samples but also inhibited the aggregation response of normal platelets to adenosine diphosphate (ADP) and collagen. Thus the inhibitory effect of high heparin concentrations was not specific for HIT. Platelets from different donors varied in their response to HIT-positive plasma and heparin; three donors were identified whose platelets did not respond to any HIT-positive plasma. The rest of the donors' platelets responded to HIT-positive plasma but varied in the degree of aggregation. These findings indicate that the source of heparin used for ex vivo assays does not affect the assay results but that selection of donors does have a significant impact on the outcome. Under appropriate conditions, platelet aggregation appears to be a sensitive and specific assay for the diagnosis of HIT.