Device manufacturers and regulatory agencies currently utilize expensive and often inconclusive in vivo vascular implant models to assess implant material thrombogenicity. We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane™ 80A polyurethane, Pebax®), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood‐contact use conditions and the variables: material (M), material surface modification (SM) with heparin, model (Mo), time (T), blood donor (D), exposure ratio (ER; cm² material/ml blood), heparin anticoagulation (H), and blood draw/fill technique (DT). Two models were used: (1) a gentle‐agitation test tube model and (2) a pulsatile flow closed‐loop model. Thrombogenicity measurements included thrombin generation (thrombin‐antithrombin complex [TAT] and human prothrombin fragment F1.2), platelet activation (β‐thromboglobulin), and platelet counts. We report that: (a) thrombogenicity was strongly dependent (p < .0001) on M, H, and T, and variably dependent (p < .0001 – > .05) on Mo, SM, and D (b) differences between positive control, test, and negative control materials became less pronounced as H increased from 0.6 to 2.0 U/ml, and (c) in vitro‐to‐in vivo case comparisons showed consistency in thrombogenicity rankings on materials classified to be of low, moderate, and high concern. In vitro methods using fresh human blood are therefore scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity.

中文翻译：

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医疗器械材料血栓形成性评估的体外方法：使用条件和生物分析概念验证方法。


设备制造商和监管机构目前利用昂贵且通常不确定的体内血管植入模型来评估植入材料的血栓形成性。我们报告了一种体外血栓形成性评估方法，其中将测试材料（聚乙烯、Elasthane™ 80A 聚氨酯、Pebax®）以及阳性对照（硼硅酸盐玻璃）和阴性对照（无材料）暴露于新鲜人血，并注意普通血液。接触使用条件和变量：材料 (M)、肝素材料表面改性 (SM)、模型 (Mo)、时间 (T)、献血者 (D)、暴露比 (ER；cm ²材料/ml 血液)、肝素抗凝 (H) 和抽血/填充技术 (DT)。使用两种模型：（1）温和搅拌试管模型和（2）脉动流闭环模型。血栓形成性测量包括凝血酶生成（凝血酶抗凝血酶复合物 [TAT] 和人凝血酶原片段 F1.2）、血小板活化（β-凝血球蛋白）和血小板计数。我们报告：(a) 血栓形成强烈依赖于 ( p < .0001) M、H 和 T，并且不同程度地依赖于 ( p < .0001 – > .05) Mo、SM 和 D (b) 之间的差异随着 H 从 0.6 U/ml 增加到 2.0 U/ml，阳性对照、测试和阴性对照材料变得不那么明显，并且 (c) 体外与体内病例比较显示，被分类为低、中度材料的血栓形成性排名具有一致性，并受到高度关注。因此，与筛选血管内材料和装置的血栓形成性的体内方法相比，使用新鲜人血的体外方法在科学上是合理的且具有成本效益。