ROLE OF COLLAGEN-ADHERENT PLATELETS IN MEDIATING FIBRIN FORMATION IN FLOWING WHOLE-BLOOD
ROLE OF COLLAGEN-ADHERENT PLATELETS IN MEDIATING FIBRIN FORMATION IN FLOWING WHOLE-BLOOD
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DOI：
10.1182/blood.v86.10.3815.bloodjournal86103815
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发表时间：
1995-11-15
期刊：
影响因子：
20.3
通讯作者：
BAUMGARTNER, HR
中科院分区：
文献类型：
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作者：
KIRCHHOFER, D;TSCHOPP, TB;BAUMGARTNER, HR
活化的血小板为凝固酶复合物提供组装位点，并以这种方式介导止血和血栓形成期间的凝固。在这项研究中，我们研究了血小板直接粘附到纤维胶原蛋白，一个主要的血栓形成成分的内皮下的促凝活性。为此，我们使用了一个人离体血栓形成模型，其中胶原蛋白涂层盖玻片暴露于流动的非抗凝血液（剪切速率，65/s）5.5分钟，这导致粘附血小板，血小板血栓和纤维蛋白的沉积。为了仅检查粘附血小板的促凝血活性，通过混合装置输注血小板GPIIb-IIIa复合物的选择性拮抗剂Ro 44-9883，导致血小板血栓形成的完全消除，但保留胶原粘附血小板层完整，与未输注抑制剂的对照实验（95 +/- 13 ng/mL）相比，该血小板层产生了增加的后室纤维蛋白肽A（FPA）水平（203 +/- 33 ng/mL）。纤维蛋白纤维的免疫组化染色进一步表明，粘附的血小板形成纤维蛋白纤维形成的细胞核，这种纤维蛋白沉积的增加是由内因子X介导的（F.X）粘附的单个血小板上的活化复合物，因为几乎完全抑制FPA生成（9 ng/mL）和纤维蛋白沉积（0.4% +/- 0.2%覆盖率）在GP IIb-IIIa拮抗剂和活性位点抑制的F. IXa共同输注后达到。在对照实验中沉积的大血小板血栓不含显著量的免疫可检测的纤维蛋白，除了在血栓基底处，粘附的血小板将血栓锚定到胶原蛋白表面。这些结果表明，胶原蛋白粘附的血小板通过为F，X活化复合物提供组装位点而在血栓形成的初始阶段是重要的凝血促进剂。(C)1995年，美国血液学会。
Activated platelets provide assembly sites for coagulation enzyme complexes and in this way can mediate coagulation during hemostasis and thrombosis. In this study, we examined the procoagulant activity of platelets adhering directly to fibrillar collagen, a main thrombogenic constituent of subendothelium. For this purpose, we used a human ex-vivo thrombosis model in which collagen-coated coverslips were exposed to flowing nonanticoagulated blood (shear rate, 65/s) for 5.5 minutes, which led to the deposition of adherent platelets, platelet thrombi, and fibrin. To examine the procoagulant activity of adherent platelets only, a selective antagonist of the platelet GPIIb-IIIa complex, Ro 44-9883, was infused via a mixing device, resulting in a complete abrogation of platelet thrombus formation but leaving the collagen-adherent platelet layer intact, This platelet layer generated increased postchamber fibrinopeptide A (FPA) levels (203 +/- 33 ng/mL) as compared with control experiments without infusion of inhibitor (95 +/- 13 ng/mL). Concomitantly, fibrin deposition measured by morphometric analysis of cross-sections was also increased, as was the platelet adhesion to collagen, An immunochemical staining of fibrin fibers further showed that the adherent platelets formed the nuclei for fibrin fiber formation, This increase in fibrin deposition was mediated by the intrinsic factor X (F.X) activation complex on adherent single platelets, because almost complete inhibition of FPA generation (9 ng/mL) and fibrin deposition (0.4% +/- 0.2% coverage) was achieved upon coinfusion of the GP IIb-IIIa antagonist and active site-inhibited F.IXa. The large platelet thrombi that were deposited in control experiments contained no significant amounts of immunodetectable fibrin except at the thrombus base, where adherent platelets anchored the thrombi to the collagen surface, These results suggest that the collagen-adherent platelets are important promoters of coagulation during the initial phase of thrombogenesis by providing assembly sites for the F,X activation complex. (C) 1995 by The American Society of Hematology.