FIBRIN AND FIBRINOLYSIS IN THROMBOTIC DISEASE

项目5涉及实验室观察的转化研究 特别是关于可溶性纤维蛋白（SF）测量 在体外和高凝状态患者中， 纤维蛋白溶解和血栓预防治疗。瞄准1“以评估输入 体外基础和可溶性的诊断和预后的有效性 急性和慢性血栓前状态下的纤维蛋白测量” 包括三个不同的部分。第一个是关于 纤维蛋白原和纤维蛋白诱导的纤维蛋白衍生物以及 凝血酶、因子XIIIa和纤溶酶，尤其是SF，使用特异性 免疫学和功能学方法。第二种是利用这个 急性高凝综合征（DIC）患者的信息 急性脓毒症或多发性创伤以及接受内毒素的志愿者 输液在第三部分中，SF的预后重要性将是 在慢性高凝状态患者中进行评估，包括 易发生DVT的乳腺恶性肿瘤患者和 易复发MI或冠心病死亡的急性MI患者。目的2 “严格评估新的血栓预防和纤维蛋白溶解 治疗”包括三项随机试验。第一个扩展了我们的 中心静脉导管血栓的临床观察 低剂量华法林预防。纤溶研究评价纤溶酶原 扩大外周动脉闭塞（PAO）的UK治疗， 经导管输注尿激酶治疗DVT与尿激酶给药的比较 静脉注射一些研究正在进行中（纤溶酶原 补充UK用于PAO），最近已启动其他（SF 中心静脉导管的结构检查、预防 血栓形成，弥散性血管内凝血患者的SF研究，SF的预后价值 复发性冠状动脉事件，SF作为 乳腺恶性肿瘤的高凝状态），一项研究处于试点阶段 阶段，计划启动前瞻性研究（导管与IV 英国DVT管理）。这些翻译研究将 严格评价SF作为诊断和预后标志物的作用 用于微血管、动脉和静脉血栓性疾病， 有效预防DVT的既往观察结果 导管以及PAO和DVT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.