Mk. Horne et Kj. Hutchison, SIMULTANEOUS BINDING OF HEPARIN AND PLATELET-FACTOR-4 TO PLATELETS - FURTHER INSIGHTS INTO THE MECHANISM OF HEPARIN-LNDUCED THROMBOCYTOPENIA, American journal of hematology, 58(1), 1998, pp. 24-30
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.