FIBRIN AND FIBRINOLYSIS IN THROMBOTIC DISEASE

项目5涉及实验室观察的翻译研究。 特别是关于可溶性纤维蛋白(SF)的测量 体外和在高凝状态患者中的研究 纤溶和血栓预防治疗。目标1“评估内部 可溶性血凝素的体外基础及其诊断和预后有效性 急性和慢性血栓前状态的纤维蛋白测定 包括三个截然不同的部分。第一个是关于……的被动反应 纤维蛋白原和纤维蛋白衍生物诱导的纤维蛋白和 凝血酶、XIIIA因子和纤溶酶，特别是SF，使用特定的 免疫学和功能性方法。第二个利用了这一点 急性高凝综合征(DIC)患者的相关信息 急性脓毒症或合并多发创伤和接受内毒素治疗的志愿者 输液。在第三部分中，SF的预测重要性将是 对慢性高凝状态患者的评估，包括 易发生深静脉血栓的乳房恶性肿瘤患者和 易复发心肌梗死或冠状动脉死亡的急性心肌梗死患者。目标2 “严格评估新的血栓预防和纤溶药物 治疗“包括三个随机试验。第一个延长了我们的 中心静脉导管血栓形成的临床观察 小剂量华法林预防。纤溶研究评估纤溶酶原 扩大UK治疗外周动脉闭塞(PAO)和 经导管给药治疗深静脉血栓形成与经导管给药的比较 静脉注射。一些研究正在顺利进行(纤溶酶原 英国对PAO的补充)，其他已于最近启动(SF 中心静脉置管的结构调查及预防 血栓形成，弥散性血管内凝血患者的SF研究，SF对DIC预后的价值 冠脉再发事件和SF作为标记物 乳腺癌中的高凝状态)，其中一项研究正在进行中 阶段，计划启动一项前瞻性研究(导管与静脉 英国DVT管理局)。这些翻译研究将 严格评估SF作为诊断和预后标志物的作用 用于微血管、动脉和静脉血栓形成疾病，并应用我们的 关于有效预防DVT的先前观察结果 动脉血栓和深静脉血栓的溶栓治疗。

Project 5 deals with translational research of laboratory observations to the patient, specifically regarding soluble fibrin (SF) measurements in vitro and in patients with hypercoagulable states and novel fibrinolytic and thromboprophylactic treatments. Aim 1 "to asses the in vitro foundation and the diagnostic and prognostic validity of soluble of fibrin measurement in acute and chronic pro-thrombotic states" includes three distinct sections. The first deals with the reactive of derivatives of fibrinogen and fibrin induced and fibrin induced by thrombin, factor XIIIa and plasmin, especially SF, using specific immunologic and functional approaches. The second utilizes this information to acute hypercoagulable syndromes (DIC) in patients with acute sepsis or with multi-trauma and in volunteers receiving endotoxin infusion. In the third part, the prognostic importance of SF will be assessed in patients with chronic hypercoagulable states, including those with breast malignancy who are prone to develop DVT and those with acute MI who are predisposed to recurrent MI or coronary death. Aim 2 "to critically evaluate new thromboprophylactic and fibrinolytic therapies" includes three randomized trials. The first extends our observations on central venous catheter thrombi to a clinical trial of low-dose warfarin prophylaxis. Fibrinolytic studies evaluate plasminogen amplification of UK therapy for peripheral arterial occlusion (PAO) and catheter-delivery of UK for DVT in comparison with UK administered intravenously. Some studies are well underway (plasminogen supplementation of UK for PAO), others have been recently initiated (SF structural investigations, prophylaxis of central venous catheter thrombosis, SF studies in patients with DIC, prognostic value of SF for recurrent coronary artery events, and SF as a marker of hypercoagulability in breast malignancy), and one study is in the pilot phase, with plans to initiate a prospective study (catheter versus IV administration of UK for DVT). These translational studies will critically evaluate the role of SF as a diagnostic and prognostic marker for microvascular, arterial and venous thrombotic disease and apply our prior observations to effective prevention of DVT associated with catheters and to thrombolytic management of PAO and DVT.