Sidelmann Johannes J, Kluft Cornelis, Krug Andrea H, Winkler Ulrich, Jespersen Jørgen, Gram Jørgen B
J. J. Sidelmann, Unit for Thrombosis Research, Department of Public Health, Faculty of Health Science, University of Southern Denmark, Niels Bohrs Vej 9, DK-6700 Esbjerg, Denmark, Tel.: +45 79182415, Fax: +45 79182430, E-mail:
Thromb Haemost. 2017 Apr 3;117(4):700-705. doi: 10.1160/TH16-10-0748. Epub 2017 Feb 2.
Fibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism. The study included 70 women treated with seven different OC-formulations. Blood was collected at baseline and after six months of OCs. The plasma concentration of fibrinogen, thrombin-antithrombin complex (TAT), plasminogen, plasmin-antiplasmin complex (PAP), D-Dimer and thrombin generation measures were determined. Fibrin structure measures and fibrin clot lysis not affected by the plasma concentration of plasminogen activators and inhibitors were determined. OCs increased the concentration of fibrinogen, TAT, plasminogen, PAP and D-dimer significantly and affected measures of thrombin generation (p<0.001). The maximal optical density of fibrin (p<0.001), the fibrin fibre density (p=0.03), fibrin fibre diameter (p=0.003), fibrin mass-length ratio (p<0.001) and lysis per hour (p<0.001) increased significantly upon OC-treatment. Lysis per hour was not correlated to the concentration of plasminogen. We conclude that the effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC. These alterations may counterbalance the OC-induced increased thrombin generation and reduced coagulation inhibitory potential, contributing to maintenance of the haemostatic balance in women receiving OCs.
纤维蛋白代谢受多种因素影响。纤维蛋白形成的速度、基因多态性、纤维蛋白溶解特性以及纤维蛋白凝块的结构是纤维蛋白周转的决定因素。口服避孕药(OCs)通过增加凝血因子、纤溶酶原和组织纤溶酶原激活物活性的浓度,并降低止血抑制剂的浓度,对止血系统有显著影响。本研究探讨了OCs对纤维蛋白结构和纤维蛋白代谢的影响。该研究纳入了70名接受七种不同OC制剂治疗的女性。在基线时以及使用OCs六个月后采集血液。测定纤维蛋白原、凝血酶 - 抗凝血酶复合物(TAT)、纤溶酶原、纤溶酶 - 抗纤溶酶复合物(PAP)、D - 二聚体的血浆浓度以及凝血酶生成指标。测定不受纤溶酶原激活物和抑制剂血浆浓度影响的纤维蛋白结构指标和纤维蛋白凝块溶解情况。OCs显著增加了纤维蛋白原、TAT、纤溶酶原、PAP和D - 二聚体的浓度,并影响凝血酶生成指标(p<0.001)。经OC治疗后,纤维蛋白的最大光密度(p<0.001)、纤维蛋白纤维密度(p = 0.03)、纤维蛋白纤维直径(p = 0.003)、纤维蛋白质量 - 长度比(p<0.001)和每小时溶解率(p<0.001)显著增加。每小时溶解率与纤溶酶原浓度无关。我们得出结论,OCs对凝血系统的影响通过纤维蛋白结构的改变得到平衡,促进凝块溶解,并有助于接受OC治疗的女性中已存在的纤维蛋白溶解易感性。这些改变可能抵消OC诱导的凝血酶生成增加和凝血抑制潜能降低,有助于维持接受OC治疗女性的止血平衡。