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 p...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003534 |
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| author | Konrad van der Zwet Mark Roest Dana Huskens Roger E.G. Schutgens Lize F.D. van Vulpen Kathelijn Fischer Rolf T. Urbanus |
| author_facet | Konrad van der Zwet Mark Roest Dana Huskens Roger E.G. Schutgens Lize F.D. van Vulpen Kathelijn Fischer Rolf T. Urbanus |
| author_sort | Konrad van der Zwet |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b633d81a9f184c4f9fc877e702a64bde |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-b633d81a9f184c4f9fc877e702a64bde2025-01-04T04:56:47ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102658No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapyKonrad van der Zwet0Mark Roest1Dana Huskens2Roger E.G. Schutgens3Lize F.D. van Vulpen4Kathelijn Fischer5Rolf T. Urbanus6Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Correspondence Konrad van der Zwet, Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Room C01.428, PO Box 85500, 3508 GA Utrecht, The Netherlands.Synapse Research Institute, Maastricht, The NetherlandsSynapse Research Institute, Maastricht, The NetherlandsCenter for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsCenter for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsCenter for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Pednet Haemophilia Research Foundation, Baarn, The NetherlandsCenter for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsBackground: 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.http://www.sciencedirect.com/science/article/pii/S2475037924003534drug monitoringemicizumabhemophilia Amonoclonal antibodiesthrombin generation |
| spellingShingle | Konrad van der Zwet Mark Roest Dana Huskens Roger E.G. Schutgens Lize F.D. van Vulpen Kathelijn Fischer Rolf T. Urbanus No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy Research and Practice in Thrombosis and Haemostasis drug monitoring emicizumab hemophilia A monoclonal antibodies thrombin generation |
| title | No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy |
| title_full | No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy |
| title_fullStr | No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy |
| title_full_unstemmed | No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy |
| title_short | No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy |
| title_sort | no correlation between thrombin generation and emicizumab levels implications for monitoring emicizumab therapy |
| topic | drug monitoring emicizumab hemophilia A monoclonal antibodies thrombin generation |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003534 |
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