Siller-Matula Jolanta M, Plasenzotti Roberto, Spiel Alexander, Quehenberger Peter, Jilma Bernd
Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Thromb Haemost. 2008 Sep;100(3):397-404.
Many animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species, which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05). Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.
许多动物被用于血液凝固和纤维蛋白溶解的研究,但由于物种差异,动物模型与人类健康的相关性常常受到质疑。目的是找到一种最合适的动物物种,能够最充分地模拟人类的凝血特征。通过旋转血栓弹力图(ROTEM)在全血中评估体外有无凝血酶刺激时不同物种的凝血特征差异。在少血小板血浆中测量内源性凝血酶生成。对来自五个不同物种的血液进行测量:人类、大鼠、猪、绵羊和兔子。在人类和绵羊中,无论有无凝血酶刺激,凝血时间(ROTEM)都在相同范围内,与大鼠、猪和兔子(0.2 IU)相比,导致凝血时间缩短所需的凝血酶剂量低100倍(0.002 IU)(p<0.05)。同样,人类和绵羊的内源性凝血酶潜力(ETP)也在相同范围内。兔子和人类在有无凝血酶刺激时的最大血凝块硬度相似。人类和猪在有无凝血酶刺激时的最大溶解相似。无论有无凝血酶刺激,凝血特征都存在显著的物种差异。最重要的是,绵羊的凝血时间与人类最相似,因此可能是转化凝血研究的合适物种。此外,我们的研究结果证实了猪作为研究纤维蛋白溶解途径的实验物种的潜在用途,并支持兔子作为研究血小板的物种的用途。