Leebeek F W, Kluft C, Knot E A, de Maat M P, Wilson J H
Department of Internal Medicine II, University Hospital Rotterdam, Dijkzigt, The Netherlands.
Gastroenterology. 1991 Nov;101(5):1382-90. doi: 10.1016/0016-5085(91)90092-y.
The aim of this study was to assess the cause of enhanced fibrinolysis in cirrhosis by studying the balance between profibrinolytic and antifibrinolytic proteins in 24 patients with mild or severe cirrhosis. Antigen levels of both tissue-type plasminogen activator and plasminogen-activator inhibitor 1 were increased in mild and severe cirrhosis. Activity levels showed a very wide variability, but median activity levels of both proteins were normal. In most patients, the increase in tissue-type plasminogen activator was counterbalanced by the increased levels of plasminogen-activator inhibitor 1, but in a subgroup of patients the change in balance resulted in extremely high tissue-type plasminogen-activator levels. The specific activity of both proteins (activity/antigen quotient) was reduced in either mild or severe cirrhosis. This finding indicates either that more enzyme-inhibitor complexes circulate in the blood of patients with cirrhosis than in normal individuals or that dysfunctional molecules circulate. Plasminogen and alpha 2-antiplasmin antigen and activity levels were decreased in both mild and severe cirrhosis. The binding of alpha 2-antiplasmin to fibrin was decreased in severe cirrhosis, making fibrin clots more susceptible to lysis. Clot lysis experiments were performed to see if equal decreases in plasminogen and alpha 2-antiplasmin levels, as found in cirrhosis, result in a change in the rate of fibrinolysis. It was found that the proportionate decreases led to enhancement of fibrinolysis, indicating that the inhibitor depletion is more important than the proenzyme depletion. The authors conclude that enhanced fibrinolysis frequently found in cirrhosis may be attributed to an increased tissue-type plasminogen-activator activity relative to plasminogen-activator-inhibitor activity and decreased levels of alpha 2-antiplasmin, resulting in a reduced binding of alpha 2-antiplasmin to fibrin.
本研究旨在通过研究24例轻度或重度肝硬化患者纤溶酶原激活蛋白和抗纤溶蛋白之间的平衡，评估肝硬化患者纤溶增强的原因。轻度和重度肝硬化患者组织型纤溶酶原激活剂和纤溶酶原激活物抑制剂1的抗原水平均升高。活性水平表现出很大的变异性，但两种蛋白的中位活性水平正常。在大多数患者中，组织型纤溶酶原激活剂的增加被纤溶酶原激活物抑制剂1水平的升高所抵消，但在一部分患者中，平衡变化导致组织型纤溶酶原激活剂水平极高。轻度或重度肝硬化患者两种蛋白的比活性（活性/抗原商）均降低。这一发现表明，要么肝硬化患者血液中循环的酶-抑制剂复合物比正常个体更多，要么循环的是功能失调的分子。轻度和重度肝硬化患者纤溶酶原和α2-抗纤溶酶的抗原及活性水平均降低。重度肝硬化患者α2-抗纤溶酶与纤维蛋白的结合减少，使纤维蛋白凝块更易溶解。进行凝块溶解实验，以观察肝硬化患者纤溶酶原和α2-抗纤溶酶水平同等降低是否会导致纤溶速率改变。结果发现，成比例的降低导致纤溶增强，表明抑制剂耗竭比酶原耗竭更重要。作者得出结论，肝硬化患者常见的纤溶增强可能归因于组织型纤溶酶原激活剂活性相对于纤溶酶原激活物抑制剂活性增加以及α2-抗纤溶酶水平降低，导致α2-抗纤溶酶与纤维蛋白的结合减少。
