Thrombin generation (TG) assays are used widely to investigate both diseases and drugs that impact thrombosis and bleeding. TG assays were also instrumental in the identification of thrombogenic impurities in immune globulin products, which were associated with thrombotic adverse events in patients. TG assays are therefore now used by quality control laboratories of plasma derivative drug manufacturers and regulatory agencies responsible for the safety testing and release of immune globulin products. In this protocol, we describe a robust and sensitive version of the TG assay for quantitative measurement of thrombogenic activity in immune globulin products. Compared with the version of the assay commonly used in clinical laboratories that compares individual patient plasma samples with normal donor samples, our TG assay is suitable for quick (170–260 min) semiautomated analysis of multiple drug samples against the World Health Organization international standard for factor XIa. Commercially available reagents can be used for the assay, and it does not require specialized equipment. The protocol can be easily adapted for the measurement of the procoagulant activity of other biopharmaceuticals, e.g., coagulation factors.

凝血酶生成 (TG) 测定广泛用于研究影响血栓形成和出血的疾病和药物。TG 检测也有助于鉴定免疫球蛋白产品中的血栓形成杂质，这些杂质与患者的血栓形成不良事件有关。因此，TG 检测现在被血浆衍生物药物制造商的质量控制实验室和负责免疫球蛋白产品安全测试和发布的监管机构使用。在本协议中，我们描述了一种强大且灵敏的 TG 检测版本，用于定量测量免疫球蛋白产品中的血栓形成活性。与临床实验室常用的将个体患者血浆样本与正常供体样本进行比较的检测方法相比，我们的 TG 测定适用于根据世界卫生组织国际标准因子 XIa 对多种药物样品进行快速（170-260 分钟）半自动分析。可以使用市售试剂进行检测，不需要专门的设备。该协议可以很容易地适应其他生物药物促凝活性的测量，例如凝血因子。