Horne M K, Hutchison K J
Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Am J Hematol. 1998 May;58(1):24-30. doi: 10.1002/(sici)1096-8652(199805)58:1<24::aid-ajh5>3.0.co;2-2.
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.
肝素诱导的血小板减少症（HIT）由针对血小板因子4（PF4）与肝素复合物的抗体介导。尽管一直认为这些复合物与血小板结合并为抗体提供靶点，但这从未得到证实。此外，有证据表明肝素 - PF4复合物不与血小板结合。我们分析了每种配体对另一种配体与血小板结合的影响。我们特别关注肝素和PF4处于等摩尔浓度时的结果，因为我们之前表明这是血小板表面HIT - IgG增加的条件。我们发现，当PF4的摩尔浓度接近或超过肝素时，这些配体同时与细胞结合，HIT - IgG也会结合。然而，当肝素摩尔过量时，PF4结合和HIT - IgG结合都会减少。我们的数据与以下假设一致：肝素 - PF4复合物通过其肝素成分与血小板膜上的肝素结合位点结合，而不是通过其PF4成分与PF4位点结合。促进复合物结合的条件也会导致HIT - IgG的结合。
