Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices
Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices
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DOI：
10.1007/s10047-017-1003-4
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发表时间：
2018-06-01
影响因子：
1.3
通讯作者：
Tatsumi, Eisuke
中科院分区：
文献类型：
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作者：
Mizuno, Toshihide;Tsukiya, Tomonori;Tatsumi, Eisuke
几种家畜被用于临床前研究，评估医疗器械的安全性和可行性；然而，动物模型与人类健康的相关性往往并不清楚。本研究的目的是比较动物模型的凝血参数，以确定哪种动物最能充分模拟人类的凝血参数。使用凝血激活剂，如组织因子（外源性凝血筛选试验，EXTEMA (R)）和部分凝血活酶磷脂（内在凝血筛选试验，IINTEMA (R)），通过体外血栓弹性成像评估全血中不同物种的凝血参数。测量使用了人类（n = 13）、小牛（n = 18）、山羊（n = 56）和猪（n = 8）的正常血液样本。犊牛的外在凝血时间（CT）和内在凝血时间（CT）较人类显著延长（分别为249.9 +/- 91.3和376.4 +/- 124.4 s vs. 63.5 +/- 11.8和192.5 +/- 29.0 s, p < 0.01）。家畜(EXTEMA （R): 77 ~ 87 mm, IINTEMA (R): 66 ~ 78 mm）的最大凝块硬度（MCF）显著高于人(EXTEMA (R): 59.1 +/- 6.0 mm, IINTEMA (R): 58.8 +/- 1.5 mm, p < 0.01)，犊牛和山羊的最大凝块硬度（MCF-t）时间比人和猪长（p < 0.01）。我们的研究结果表明，四种植物的外在凝血参数和内在凝血参数存在相关差异。这些交叉比较表明，有必要在临床前动物研究中阐明凝血特性的特征。
Several species of domestic animals are used in preclinical studies evaluating the safety and feasibility of medical devices; however, the relevance of animal models to human health is often not clear. The purpose of this study was to compare the clotting parameters of animal models to determine which animals most adequately mimic human clotting parameters. The clotting parameters of the different species were assessed in whole blood by in vitro thromboelastography using the clotting activators, such as tissue factor (extrinsic clotting screening test, EXTEMA (R)) and partial thromboplastin phospholipid (intrinsic clotting screening test, IINTEMA (R)). The measurements were performed using normal blood samples from humans (n = 13), calves (n = 18), goats (n = 56) and pigs (n = 8). Extrinsic clotting time (CT) and the intrinsic CT were significantly prolonged in calves compared to humans (249.9 +/- 91.3 and 376.4 +/- 124.4 s vs. 63.5 +/- 11.8 and 192.5 +/- 29.0 s, respectively, p < 0.01). The maximum clot firmness (MCF) in domestic animals (EXTEMA (R): 77-87 mm, IINTEMA (R): 66-78 mm) was significantly higher than that of humans (EXTEMA (R): 59.1 +/- 6.0 mm, IINTEMA (R): 58.8 +/- 1.5 mm, p < 0.01), and calves and goats exhibited longer time to MCF (MCF-t) than did humans and pigs (p < 0.01). Our results show that there are relevant differences in the four species' extrinsic and intrinsic clotting parameters. These cross-comparisons indicate that it is necessary to clarify characteristics of clotting properties in preclinical animal studies.