van der Zwet Konrad, Roest Mark, Huskens Dana, Schutgens Roger E G, van Vulpen Lize F D, Fischer Kathelijn, Urbanus Rolf T
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Synapse Research Institute, Maastricht, The Netherlands.
Res Pract Thromb Haemost. 2024 Dec 17;9(1):102658. doi: 10.1016/j.rpth.2024.102658. eCollection 2025 Jan.
Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.
To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.
A single-center longitudinal cohort study was conducted, with samples collected during the steady-state phase of emicizumab therapy. TG was measured using tissue factor (TF; TF-TG, 1 pM) and FXIa (FXIa-TG, 200 pM). Emicizumab concentrations were determined with mass spectrometry. Only treated bleeds were recorded. Pearson correlations (rho, ) were reported.
Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG ( = 0.42) showed a borderline correlation, and FXIa-TG ( = 0.15) showed no correlation with emicizumab concentrations. Although FXIa-TG showed a 9% higher endogenous thrombin potential in patients with zero vs ≥1 treated bleed (endogenous thrombin potential: 957 vs 878 nM/min, = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.
TG parameters showed no clinically relevant correlations with emicizumab plasma concentrations, were not associated with traumatic bleeding, and showed considerable intrapatient variability. Therefore, TG was not considered useful for monitoring coagulation potential in patients on steady-state emicizumab prophylaxis.
艾美赛珠单抗是一种模拟因子（F）VIII的双特异性抗体，显著改善了A型血友病的治疗。虽然可以测量艾美赛珠单抗水平，但缺乏评估其止血效果的工具。凝血酶生成（TG）测定可区分接受FVIII预防治疗的A型血友病患者的出血表型，也可用于艾美赛珠单抗治疗期间。
评估接受艾美赛珠单抗治疗的患者中TG参数、艾美赛珠单抗水平与出血之间的关联。
进行了一项单中心纵向队列研究，在艾美赛珠单抗治疗的稳态期采集样本。使用组织因子（TF；TF-TG，1 pM）和FXIa（FXIa-TG，200 pM）测量TG。用质谱法测定艾美赛珠单抗浓度。仅记录治疗过的出血事件。报告Pearson相关性（rho，）。
在艾美赛珠单抗治疗的中位1年期间，分析了来自49名患者的85份样本。大多数出血为创伤性（97%；= 30），而1次出血为自发性。在12个月时，TF-TG（= 0.42）显示出临界相关性，FXIa-TG（= 0.15）与艾美赛珠单抗浓度无相关性。虽然FXIa-TG显示，与有≥1次治疗出血的患者相比，未发生治疗出血的患者的内源性凝血酶潜力高9%（内源性凝血酶潜力：957 vs 878 nM/min，= 0.045），但FXIa峰值高度和TF-TG均与创伤性出血无任何关联。
TG参数与艾美赛珠单抗血浆浓度无临床相关相关性，与创伤性出血无关，且在患者内存在相当大的变异性。因此，TG不被认为对监测接受稳态艾美赛珠单抗预防治疗的患者的凝血潜力有用。
