Ries M, Klinge J, Rauch R, Keuper H, Harms D
Klinik mit Poliklinik für Kinder und Jugendliche, Universität Erlangen-Nürnberg, Deutschland.
Biol Neonate. 1996;69(5):298-306. doi: 10.1159/000244324.
The fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Newborn's plasminogen differs from adult plasminogen in carbohydrate composition, cell binding and activation kinetics. The fetal plasminogen has an increased concentration of sialic acid similar to fetal fibrinogen. In a previously reported study on plasminogen activation kinetics, we demonstrated differences in the reaction kinetics between fetal plasmin and plasmin inhibitors as compared to the reaction between adult plasmin and inhibitors. Hitherto, there are no investigations on the role of alpha 2-antiplasmin in the inhibition of clot lysis in newborns. We studied the contributions of purified alpha 2-antiplasmin to the regulation of fibrin clot lysis by use of a microtiter clot lysis assay. The lysis time of clots without adding purified alpha 2-antiplasmin correlated to the activator dose. When purified alpha 2-antiplasmin was incorporated at final concentrations ranging from 10 to 40 micrograms/ml, strong dose-dependent inhibition resulting in a prolongation of 50% lysis time was observed. The inhibition in newborns at all alpha 2-antiplasmin concentrations was less pronounced than that of the adults if 50% lysis time was < 55 min. If 50% lysis time was > 55 min. the prolongation of 50% lysis time was more pronounced in newborn than in adult plasma. The fact that we have less effects of alpha 2-antiplasmin in newborn infants at short reaction times despite the lower plasminogen levels, is consistent with slower reaction kinetics between plasmin and alpha 2-antiplasmin in newborns. These differences raise an explanation for the findings of Idell et al. [Am J Respir Crit Care Med 1994; 149:767-775] in premature baboons with neonatal respiratory distress syndrome (RDS). The knowledge of different reaction kinetics between plasmin and alpha 2-antiplasmin and the role of alpha 2-antiplasmin in the inhibition of clot lysis in newborns can be helpful to elucidate the significance of the fetal fibrinolytic system in neonatal RDS and to establish treatment strategies for fibrinolytic therapy of progressive RDS.
纤维蛋白溶解系统参与多种生物学现象，与大龄儿童或成人相比，新生儿的生理情况有所不同。新生儿的纤溶酶原在碳水化合物组成、细胞结合和激活动力学方面与成人纤溶酶原不同。胎儿纤溶酶原的唾液酸浓度增加，类似于胎儿纤维蛋白原。在先前报道的一项关于纤溶酶原激活动力学的研究中，我们证明了胎儿纤溶酶与纤溶酶抑制剂之间的反应动力学与成人纤溶酶和抑制剂之间的反应存在差异。迄今为止，尚未有关于α2 -抗纤溶酶在新生儿凝血块溶解抑制中作用的研究。我们使用微量滴定凝血块溶解试验研究了纯化的α2 -抗纤溶酶对纤维蛋白凝块溶解调节的贡献。不添加纯化α2 -抗纤溶酶时凝块的溶解时间与激活剂剂量相关。当以10至40微克/毫升的终浓度加入纯化的α2 -抗纤溶酶时，观察到强烈的剂量依赖性抑制，导致50%溶解时间延长。如果50%溶解时间<55分钟，在所有α2 -抗纤溶酶浓度下，新生儿的抑制作用比成人弱。如果50%溶解时间>55分钟，新生儿血浆中50%溶解时间的延长比成人更明显。尽管新生儿纤溶酶原水平较低，但在短反应时间内α2 -抗纤溶酶对新生儿的影响较小，这一事实与新生儿纤溶酶和α2 -抗纤溶酶之间较慢的反应动力学一致。这些差异为伊德尔等人[《美国呼吸与危重症医学杂志》1994年；149:767 - 775]在患有新生儿呼吸窘迫综合征（RDS）的早产狒狒中的研究结果提供了解释。了解纤溶酶和α2 -抗纤溶酶之间不同的反应动力学以及α2 -抗纤溶酶在新生儿凝血块溶解抑制中的作用，有助于阐明胎儿纤维蛋白溶解系统在新生儿RDS中的意义，并为进行性RDS的纤维蛋白溶解治疗制定治疗策略。
