凝血酶生成与半蜜珠单抗水平无相关性：监测半蜜珠单抗治疗的意义。

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-01-01 DOI:10.1016/j.rpth.2024.102658

Konrad van der Zwet , Mark Roest , Dana Huskens , Roger E.G. Schutgens , Lize F.D. van Vulpen , Kathelijn Fischer , Rolf T. Urbanus

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引用次数: 0

摘要

背景：Emicizumab是一种模拟因子(F)VIII的双特异性抗体，可显著改善a型血友病的治疗。虽然可以测量emicizumab的水平，但缺乏估计emicizumab止血功效的工具。凝血酶生成（TG）测定可以在FVIII预防中区分血友病A患者的出血表型，也可以在半蜜单抗治疗期间使用。目的：评估接受艾美珠单抗治疗的患者TG参数、艾美珠单抗水平和出血之间的关系。方法：进行单中心纵向队列研究，在半单抗治疗的稳态阶段收集样本。用组织因子(TF；TF-TG, 1 pM)和FXIa （FXIa- tg, 200 pM）。用质谱法测定Emicizumab浓度。只记录治疗后的出血。Pearson相关性（rho, r）被报道。结果：在中位1年的半单抗治疗期间，分析了来自49例患者的85个样本。大多数出血是外伤性的(97%；N = 30)，自发性出血1例。在12个月时，tnf - tg （r = 0.42）显示出临界相关性，FXIa-TG （r = 0.15）与半珠单抗浓度无相关性。虽然FXIa-TG在治疗为0和≥1的出血患者中显示出9%的内源性凝血酶电位（内源性凝血酶电位：957 vs 878 nM/min， P = 0.045），但fxia峰高度和TF-TG均未显示出与创伤性出血的任何关联。结论：TG参数与emicizumab血药浓度无临床相关性，与外伤性出血无相关性，且表现出相当大的患者内变异性。因此，TG被认为不能用于监测稳态emicizumab预防患者的凝血电位。

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No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy

Background

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.

Objectives

To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.

Methods

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, r) were reported.

Results

Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; n = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG (r = 0.42) showed a borderline correlation, and FXIa-TG (r = 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, P = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.

Conclusion

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.

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