Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ann Surg. 2012 Aug;256(2):306-12. doi: 10.1097/SLA.0b013e31824f9e7e.
We investigated the effect of human bile on the stability of plasma clots and of fibrin sealants.
Fibrin sealants are extensively used in liver surgery, for example, during liver resections. Although these sealants have been developed to induce hemostasis, in practice these products are actually mainly used to seal dissected bile ducts to prevent postsurgical bile leakage.
We performed in vitro assays in which clotting and lysis of human plasma clots or fibrin sealants was studied in presence or absence of human bile.
Addition of bile to human plasma resulted in a dose-dependent increase in clotting time, and a dose-dependent decrease in clot lysis time. Bile also accelerated lysis of in vitro clotted fibrin sealants. Immunodepletion of tissue-type plasminogen activator (tPA) resulted in partial depletion of the lysis promoting activity of bile. Immunodepletion of both tPA and lysine-binding proteins from bile fully abolished the lytic activity, suggesting that tPA and plasminogen present in human bile are responsible for the lysis-promoting effect. Surprisingly, addition of high dose plasminogen activator inhibitor type 1 (PAI-1) to bile did not attenuate the lytic activity toward fibrin sealants, which suggested that tPA in a biliary environment may be unsusceptible to PAI-1 inhibition. Indeed, bile acids were shown to prevent tPA from interacting with PAI-1, although preformed complexes were not destabilized upon addition of bile acids.
These combined results suggest that the presence of tPA and other fibrinolytic proteins in human bile results in lysis of plasma clots or fibrin sealants, which potentially could affect the efficacy of the latter products.
研究人胆汁对血浆凝块和纤维蛋白密封剂稳定性的影响。
纤维蛋白密封剂在肝外科中广泛应用，例如在肝切除术中。尽管这些密封剂是为了诱导止血而开发的，但实际上在实践中，这些产品主要用于密封解剖的胆管，以防止术后胆漏。
我们进行了体外检测，研究了人胆汁存在或不存在时人血浆凝块或纤维蛋白密封剂的凝固和溶解。
胆汁与人血浆混合后，凝血时间呈剂量依赖性增加，凝血溶解时间呈剂量依赖性减少。胆汁还加速了体外凝固的纤维蛋白密封剂的溶解。组织型纤溶酶原激活物(tPA)的免疫耗竭导致胆汁促溶解活性部分耗竭。从胆汁中免疫耗竭 tPA 和赖氨酸结合蛋白完全消除了溶血性活性，表明胆汁中存在的 tPA 和纤溶酶原是促进溶解的原因。令人惊讶的是，向胆汁中添加高剂量的纤溶酶原激活物抑制剂 1(PAI-1)并没有减弱对纤维蛋白密封剂的溶血性活性，这表明在胆汁环境中 tPA 可能不易受到 PAI-1 抑制。事实上，胆汁酸被证明可以防止 tPA 与 PAI-1 相互作用，尽管添加胆汁酸后不会破坏预形成的复合物。
这些综合结果表明，人胆汁中存在 tPA 和其他纤维蛋白溶解蛋白会导致血浆凝块或纤维蛋白密封剂溶解，这可能会影响后者产品的疗效。
