Reed G L, Matsueda G R, Haber E
Massachusetts General Hospital, Boston 02114.
Thromb Haemost. 1992 Sep 7;68(3):315-20.
Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.
血小板凝块可抵抗纤溶酶原激活剂介导的纤维蛋白溶解。我们推测血小板因子XIII可能通过催化α2-抗纤溶酶（α2AP）与纤维蛋白的交联来增强富含血小板凝块的纤维蛋白溶解抗性。通过聚丙烯酰胺凝胶电泳和免疫印迹分析血浆凝块结构发现，与血小板减少的血浆凝块相比，富含血小板的血浆凝块中α2AP-纤维蛋白交联加速。一项对用纯化纤维蛋白原（缺乏因子XIII活性）、分离的血小板和特异性因子XIII抑制剂形成的凝块进行的类似研究表明，这种加速交联是由于血小板因子XIII的催化活性。此外，当洗涤后的血小板被凝血酶聚集时，有证据表明血小板因子XIII介导了血小板α2AP与血小板纤维蛋白（原）之间的交联。对与洗涤后的血小板聚集体相关的α2AP进行特异性抑制（通过单克隆抗体）可加速血小板聚集体的纤维蛋白溶解。因此，在富含血小板的血浆凝块以及凝血酶诱导的血小板聚集体中，血小板因子XIII可积极形成α2AP-纤维蛋白交联，这似乎增强了富含血小板凝块对纤维蛋白溶解的抗性。
