Simultaneous binding of heparin and platelet factor-4 to platelets: further insights into the mechanism of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor-4 (PF4) and heparin. Although it has been 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 platelets. We have analyzed the effect of each ligand on the platelet binding of the other. We particularly focused on the result when heparin and PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT-IgG increased on the platelet surface. We found that when the molar concentration of PF4 approximates or exceeds that of heparin, the ligands bind simultaneously to the cells and HIT-IgG binds also. However, when heparin is in molar excess, both PF4 binding and HIT-IgG binding are diminished. Our data are consistent with the hypothesis that heparin-PF4 complexes bind via their heparin component to heparin binding sites on the platelet membrane rather than by their PF4 component to PF4 sites. The conditions promoting the binding of the complexes also lead to binding of HIT-IgG.
Horne
M K
MK
Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hutchison
K J
KJ
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006493:Heparin / Q000009:adverse effects* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D008024:Ligands; D009994:Osmolar Concentration; D010978:Platelet Factor 4 / Q000378:metabolism*; D013552:Swine; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*; D013997:Time Factors
D007074:Immunoglobulin G; D008024:Ligands; D010978:Platelet Factor 4; D006493:Heparin