Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin
Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin
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DOI：
10.1016/s0049-3848(01)00247-x
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发表时间：
2001-05-01
影响因子：
7.5
通讯作者：
Tobelem, G
中科院分区：
文献类型：
--
作者：
Dupuy, E;Soria, C;Tobelem, G
纤维蛋白原在止血、血栓形成和血管疾病中起着复杂的作用。高纤维蛋白原血症是一种独立的血管危险因素，异常纤维蛋白原血症可诱发血栓形成。无纤维蛋白原血症通常导致出血素质，而意外的缺血性病变则令人关注。我们报告一例无纤维蛋白原血症患者，其在30岁时出现与髂动脉和髂内动脉严重狭窄相关的足部缺血性病变。髂动脉病变的活检显示明显的肌内膜增生。我们进行了标准的止血分析，并分析了患者以及经或未经蛇毒酶处理的正常对照血浆中血小板和凝血因子的活化标志物以及凝血酶生成的动力学。闭塞性动脉病变归因于穿透血管腔的破坏性血肿。与未经处理的正常血浆相比，在无纤维蛋白原血症患者和去纤维蛋白的正常血浆中，加入钙后凝血酶浓度显著升高。凝血酶 - 抗凝血酶复合物（T - AT）显著增加，而F1 + 2凝血酶原片段保持在正常范围。这些结果表明凝血激活和体内循环凝血酶的存在。凝血酶激活血小板，血小板分泌平滑肌细胞生长因子并导致内膜增生。血管壁内的反复出血可能导致损伤和局部凝血酶生成。未被血凝块捕获的凝血酶可用于血小板激活以及平滑肌细胞迁移和增殖。内膜上缺乏保护性纤维蛋白帽可能是内膜易损和栓塞的原因。在这种矛盾的情况下，无纤维蛋白原血症似乎是一种血管危险因素。（C）2001爱思唯尔科学有限公司。保留所有权利。
Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor. (C) 2001 Elsevier Science Ltd. All rights reserved.