全膝关节置换术（TKA）为膝关节炎终末期的最佳治疗措施，失血量大是TKA围术期面临的重大难题。氨甲环酸作为抗纤溶系统止血药物，在TKA围术期被广泛应用，但给药方案尚未统一。而前期研究表明氨甲环酸的使用将增加TKA术后血栓发生风险，因此其给药方案亟需优化。本课题拟针对TKA围术期氨甲环酸暴露水平、D-二聚体等纤溶系统标记物的经时过程展开定量研究。通过引入疾病进程模型描述TKA围术期纤溶系统的自发进展。在此基础上，利用前述经时数据，建立基于群体的药动学-药效学-疾病进程模型，描述氨甲环酸的抗纤溶过程，考察相关因素对个体间变异的影响。最终预测不同给药剂量、时机、时程下氨甲环酸的效应，优化给药方案。通过考察围术期出血量、输血率及血栓发生等，验证优化方案的安全有效性。为TKA围术期氨甲环酸的合理应用提供重要理论依据。

Total knee arthroplasty (TKA) is the best therapeutic measure for end-stage osteoarthritis patients. Large blood loss is a major problem during TKA perioperative period. Tranexamic acid, an antifibrinolytic hemostatic, now widely used perioperatively in TKA patients, is effective for decreasing perioperative blood loss. But various of different regimens of tranexamic acid are used in clinic. On the other hand, using tranexamic acid perioperatively would increase the risk of venous thrombosis event after the surgery. So that, optimal dosage regimen is needed. The present study is going to determine the time course of the drug concentration and fibrinolytic biomarkers. Disease model is used to describe the time course of fibrinolytic biomarkers during TKA perioperative period. Further, in order to evaluate the patient-related factors on inter-individual variance and to obtain optimal dose, timing and frequence, population pharmacokinetic/pharmacodynamic/disease model is developed to predict the time course of biomarkers and their change in different dosage regimen. Intraoperative and postoperative blood loss, perioperative blood transfusion and postoperative thrombosis are recorded to evaluate the safety and efficacy of the optimal regimen. Afterall, the present study is to provide the important theoretical basis for the reasonable application of tranexamic acid during TKA perioperative period.