Department of Clinical Haematology, The Alfred Hospital, Melbourne, Victoria, Australia.
Department of Clinical Haematology, The Alfred Hospital, Melbourne, Victoria, Australia; Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Thromb Res. 2024 May;237:148-153. doi: 10.1016/j.thromres.2024.03.031. Epub 2024 Mar 29.
Optimal management of cardiovascular disease (CVD) in people with haemophilia (PWH) is a growing issue, given the continuing improvement in life expectancy among PWH. The evolving treatment paradigms targeting higher trough levels and the advent of non-factor replacement therapies (NFRT) means much of the 'protection' PWH were thought to have against CVD may be lost. There is a paucity of evidence regarding the safety of using anticoagulants in PWH. We designed a study assessing the thrombin generation (TG) of PWH of different severities and treatments, compared to non-haemophilia patients receiving a Factor Xa (FXa) inhibitor (apixaban or rivaroxaban), healthy controls, and assessing TG parameters of adding FXa inhibitor to the plasma of PWH receiving emicizumab prophylaxis. In total, 40 patients were included. TG was initiated with 5pM tissue factor (TF) using the calibrated automated thrombinoscope. Compared to those with mild haemophilia, patients receiving a FXa inhibitor had higher endogenous thrombin potential (ETP) (1278.42 vs 1831.36) and velocity index (40.71 vs 112.56), but both had a similar peak height (154.0 vs 262.63) and time to peak (both 5.83). People with severe haemophilia receiving emicizumab had significantly improved TG parameters compared to those not receiving emicizumab - ETP 1678.11 vs 809.96 and peak height 233.8 vs 92.05; however, when FXa inhibitor was added their TG parameters deteriorated to the severe haemophilia range (ETP 1179.60 and peak height 103.05). TG may provide additional useful information regarding the use of anticoagulants in PWH.
在接受因子 Xa（FXa）抑制剂（阿哌沙班或利伐沙班）治疗的非血友病患者、健康对照者中，评估不同严重程度和治疗方案的血友病患者的凝血酶生成（TG），并评估 FXa 抑制剂添加到接受emicizumab 预防治疗的血友病患者血浆中的 TG 参数。共有 40 名患者入组。使用校准的自动凝血酶仪，以 5pM 组织因子（TF）启动 TG。与轻度血友病患者相比，接受 FXa 抑制剂治疗的患者内源性凝血酶潜能（ETP）更高（1278.42 对 1831.36）和速度指数更高（40.71 对 112.56），但两者的峰值高度相似（154.0 对 262.63），达峰时间相似（均为 5.83）。接受emicizumab 治疗的重度血友病患者的 TG 参数明显优于未接受 emicizumab 治疗的患者-ETP 为 1678.11 对 809.96，峰值高度为 233.8 对 92.05；然而，当添加 FXa 抑制剂时，他们的 TG 参数恶化到重度血友病范围（ETP 为 1179.60，峰值高度为 103.05）。TG 可能为血友病患者使用抗凝剂提供额外的有用信息。
