Department of Cardiologic, Thoracic, and Vascular Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy.
Thromb Res. 2010 Oct;126(4):e294-7. doi: 10.1016/j.thromres.2010.07.016. Epub 2010 Aug 11.
The imbalance in clotting homeostasis, tending towards hypercoagulation, is recognized as the real barrier to the long-term survival of porcine xenografts in pig-to-primate xenotransplatation. The present study aimed to validate in primate blood the applicability of whole blood rotation thromboelastometry, performed by ROTEM®, which evaluates the characteristics of clot formation by dynamic monitoring.
ROTEM® (Pentapharm GmbH, Munich, Germany) was used to investigate native coagulation (NATEM®), the intrinsic (INTEM®) and extrinsic (EXTEM®) pathways, the function of fibrinogen (FIBTEM®), and the presence of fibrinolysis in 40 naïve cynomolgus monkeys. Using classic validation approaches, the normal thromboelastographic profile was defined and the influence of haematocrit (Hct,%), platelet count (x10(9)/L), fibrinogen (mg/dl), and factor VIII (FVIII,%) was evaluated.
In all four (NATEM®, INTEM®, EXTEM®, FIBTEM®) assays considered, Clotting Time (CT, sec) and Clot Formation Time (CFT, sec) were shorter in primates than humans. Moreover, α-angle (°), Maximum Clot Firmness (MCF, mm), and MaxVel (mm/min) were also higher in primates than humans. No substantial difference was observed for Hct and platelet count between the two species. On the contrary, FVIII was higher in primates than in humans whereas, interestingly enough, fibrinogen levels were lower in monkeys than in humans.
ROTEM® depicts a hypercoagulable profile in primates as compared to humans. Taken together these data suggest that, with regard to coagulation, xenotransplantation in cynos may represent a much more difficult situation than xenotransplantation in humans.
在猪到灵长类动物的异种移植中，凝血平衡的失衡，倾向于过度凝血，被认为是猪异种移植物长期存活的真正障碍。本研究旨在验证全血旋转血栓弹性描记术（ROTEM®）在灵长类动物血液中的适用性，该方法通过动态监测评估血栓形成的特征。
使用 ROTEM®（Pentapharm GmbH，慕尼黑，德国）来研究 40 只未致敏食蟹猴的天然凝血（NATEM®）、内在（INTEM®）和外在（EXTEM®）途径、纤维蛋白原功能（FIBTEM®）和纤溶的存在。采用经典的验证方法，定义正常的血栓弹性描记图，并评估红细胞压积（Hct，%）、血小板计数（x10(9)/L）、纤维蛋白原（mg/dl）和因子 VIII（FVIII，%）的影响。
在所有四种（NATEM®、INTEM®、EXTEM®和 FIBTEM®）考虑的测定中，凝血时间（CT，秒）和血栓形成时间（CFT，秒）在灵长类动物中均短于人类。此外，α角（°）、最大血凝块强度（MCF，mm）和最大速度（MaxVel，mm/min）在灵长类动物中也高于人类。两种物种之间 Hct 和血小板计数没有实质性差异。相反，FVIII 在灵长类动物中高于人类，而有趣的是，纤维蛋白原水平在猴子中低于人类。
与人类相比，ROTEM®描绘了灵长类动物的高凝状态。综上所述，这些数据表明，就凝血而言，在食蟹猴中的异种移植可能比在人类中更为困难。
