SIMULTANEOUS BINDING OF HEPARIN AND PLATELET-FACTOR-4 TO PLATELETS - FURTHER INSIGHTS INTO THE MECHANISM OF HEPARIN-LNDUCED THROMBOCYTOPENIA

Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor-4 (PF4) and heparin, Although it has bee n assumed that these complexes bind to platelets and provide a target for the antibody, this has never been demonstrated. Furthermore, there is evidence suggesting that heparin-PF4 complexes do not bind to plat elets. We have analyzed the effect of each ligand on the platelet bind ing of the other. We particularly focused on the result when heparin a nd PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT-IgG increased on the plate let surface. We found that when the molar concentration of PF4 approxi mates or exceeds that of heparin, the ligands bind simultaneously to t he cells and HIT-IgG binds also. However, when heparin is in molar exc ess, both PF4 binding and HIT-IgG binding are diminished. Our data are consistent with the hypothesis that heparin-PP4 complexes bind via th eir heparin component to heparin binding sites on the platelet membran e rather than by their PF4 component to PF4 sites. The conditions prom oting the binding of the complexes also lead to binding of HIT-IgG. (C ) 1998 Wiley-Liss, Inc.