Heparin immune thrombocytopenia: evidence for a heparin-platelet complex as the antigenic determinant

Profound thrombocytopenia developed in a 57 yr old man during a course of heparin therapy. Cessation of the drug led to a prompt recovery in the platelet count. Heparin added to the patient's plasma in vitro, in a final concentration as low as 0.00074 units/ml, produced platelet aggregation. The addition of either the patient's plasma or heated serum to PRP containing heparin (added either in vitro or administered in vivo) resulted in platelet aggregation. Studies performed with radiolabeled heparin and washed platelets indicated that in the presence of the patient's plasma or serum, heparin became bound to the platelets. The factor in the patient's plasma associated with this binding was nondialyzable and heat-stable (56° C for 10 min) and was precipitated by half-saturated ammonium sulfate. Coincident with the heparin-induced platelet aggregation, this factor also became bound to the platelets. Immunologic examination of platelet lysates prepared from mixtures of patient's serum, washed platelets, and labeled heparin indicated that the factor was an immunoglobulin. Our findings are consistent with the hypothesis that the patient developed an antibody directed against an antigen complex consisting of both heparin and a platelet component. We propose that the antibody, reacting with the heparin-platelet complex, triggered the platelet release reaction leading to platelet aggregation, which resulted in the thrombocytopenia.