Heparin is not required for detection of antibodies associated with heparin-induced thrombocytopenia/thrombosis

Heparin-induced thrombocytopenia (HIT), with or without thrombosis, is a co mmon and often serious complication of heparin therapy. Platelet-activating , heparin-induced antibodies characteristic of HIT are thought to be specif ic for complexes formed between platelet factor 4 (PF4) and heparin, and su ch complexes are routinely used for antibody detection. We studied the bind ing of HIT antibodies to PF4 complexed with heparin fractions of uniform mo lecular size or linear polyanions other than heparin and found that many co mpounds other than heparin form complexes with PF4 that are suitable for an tibody detection, provided they carry strong negative charges spaced about 0.5 nm apart along the molecular backbone and are of sufficient length to s pan about 40% of the circumference of the PF4 tetramer, Polyvinyl phosphona te was among the compounds that were equivalent to heparin. Thus neither a polysaccharide chain nor sulfate side groups-the hallmarks of heparin struc ture-are required for HIT antibody detection. The findings support the view that antibodies associated with HIT are specific for conformational change s that take place in the positively charged PF4 molecule when it reacts wit h a suitable, linear polyanion.