ArticleJournal of thrombosis and haemostasis : JTH2021
Thrombin generation potential in the presence of concizumab and rFVIIa, APCC, rFVIII, or rFIX: In vitro and ex vivo analyses.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Laboratory Challenges in the Era of Novel Haemophilia Therapies.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Review
- Marstacimab, an antitissue factor pathway inhibitor, combined with bypassing agents: effects on thrombin generation and in hemostatically normal rats.Research and practice in thrombosis and haemostasis · 2025Article
- Evaluation of the interference of fitusiran and antithrombin lowering in plasma on routine coagulation assays.Research and practice in thrombosis and haemostasis · 2025Article
- Activated prothrombin complex concentrate in patients receiving emicizumab prophylaxis: from evidence to clinical practice.Research and practice in thrombosis and haemostasis · 2025Review
- Concizumab, a Non-Replacement Therapy for Persons with Hemophilia with Inhibitors.Journal of clinical medicine · 2025Review
- Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies.International journal of laboratory hematology · 2025Review
- Concizumab improves clot formation in hemophilia A under flow.Journal of thrombosis and haemostasis : JTH · 2024Article
- Concizumab: First Approval.Drugs · 2023Review
- Updates on Novel Non-Replacement Drugs for Hemophilia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review.Journal of thrombosis and haemostasis : JTH · 2022Review
- Concizumab as a Subcutaneous Prophylactic Treatment Option for Patients with Hemophilia A or B: A Review of the Evidence and Patient's Perspectives.Journal of blood medicine · 2022Review
- Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases.Frontiers in cardiovascular medicine · 2022Review
- Factor X and Combined Factor VIIa/Factor X Augment Coagulation Potential in a Plasma Model of Tissue Factor Pathway Inhibitor-Reduced Haemophilia State.Haemophilia : the official journal of the World Federation of HemophiliaArticle
- Global Hemostatic Methods to Tailor Treatment With Bypassing Agents in Hemophilia A With Inhibitors- A Single-Center, Pilot Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Transforming Hemophilia Treatment With Novel Rebalancing Agents: Clinical Studies and Practical Perspectives.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe anti-tissue factor plasma inhibitor monoclonal antibody concizumab is under clinical investigation for subcutaneous prophylaxis of hemophilia A/B (HA/HB) with or without inhibitors. Breakthrough bleeds while on concizumab prophylaxis may be treated with bypassing agents (recombinant activated factor VIIa [rFVIIa] and activated prothrombin complex concentrate [APCC]), or with factor VIII (FVIII) or factor IX (FIX).
objectivesTo evaluate the effect of combining concizumab with rFVIIa, APCC, rFVIII, and rFIX on thrombin generation (TG) potential.
methodsPooled HA plasma was spiked in vitro with concizumab alone or together with rFVIIa, APCC, or rFVIII. rFVIIa, APCC, and rFVIII were added ex vivo to plasma from HA patients receiving concizumab prophylaxis. Pooled HB plasma was spiked with concizumab alone or together with rFIX. TG potential was measured after initiation with tissue factor.
resultsConcizumab increased thrombin peak in a concentration-dependent manner. Adding rFVIIa, APCC, rFVIII, or rFIX caused a further increase in thrombin peak. The effects of concizumab and rFVIIa, APCC, rFVIII, or rFIX were mainly additive, with no or up to maximally ~25% extra effect caused by drug--drug interaction. No strong synergistic effects were observed upon combining concizumab with rFVIIa, APCC, rFVIII, or rFIX. The thrombin peak obtained with 0.5 IU/ml rFVIII or rFIX in the presence of concizumab was on occasion slightly higher, but mostly comparable to the thrombin peak with 1 IU/ml rFVIII or rFIX in the absence of concizumab.
conclusionrFVIIa, APCC, rFVIII, and rFIX enhanced plasma TG potential in the presence of concizumab. Dose levels of concomitant use should be adjusted accordingly to balance potential safety concerns while maintaining the necessary hemostatic effect. Please see the video in the Supplementary Material for an animated summary of the data presented.
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