Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII
Background: The incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with...
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Elsevier
2024-10-01
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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/S2475037924002711 |
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| author | Sylvain Lamoine Vincent Jury Virginie Fourneyron Jonathan Douxfils Dorian Teissandier Laurie Talon Thomas Sinegre Aurélien Lebreton |
| author_facet | Sylvain Lamoine Vincent Jury Virginie Fourneyron Jonathan Douxfils Dorian Teissandier Laurie Talon Thomas Sinegre Aurélien Lebreton |
| author_sort | Sylvain Lamoine |
| collection | DOAJ |
| description | Background: The incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with emicizumab (routine prophylaxis), factor (F)VIII products, and DOAC. Their concomitant presence constitutes a hemostatic challenge. Recent international guidelines stated that data are scarce on the hemostatic balance of plasma samples from patients with HA receiving emicizumab and DOAC. Objectives: The aim of this observational study was to assess the coagulation of FVIII-deficient plasma spiked with DOAC and emicizumab and to evaluate the effects of FVIII addition. Methods: Prothrombin time, activated partial thromboplastin time, and thrombin generation (TG) using the calibrated automated thrombogram method were evaluated in aliquots of a commercial severe HA plasma supplemented with emicizumab (0, 12.5, 25, 50, and 100 ng/mL), DOAC (0, 50, 100, 200, and 400 ng/mL of apixaban, rivaroxaban, edoxaban, or dabigatran) and FVIII (0%, 5%, 15%, 50%, and 100%). Results: DOAC rapidly induced a TG decrease. Emicizumab could counter this effect only for the lowest DOAC dose. FVIII addition to the FVIII-deficient plasma containing a DOAC and emicizumab improved TG and countered the anticoagulant effect of DOAC at ≤100 ng/mL. Conclusion: Our findings indicate that FVIII can be safely used with emicizumab to counter the anticoagulant effect of DOAC at ≤100 ng/mL. The TG assay is an efficient tool to monitor plasma containing anti-FXa DOAC, but not dabigatran (anti-FIIa). |
| format | Article |
| id | doaj-art-cd2213ce0bf847a7b9aadd36b2934e9d |
| institution | OA Journals |
| issn | 2475-0379 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-cd2213ce0bf847a7b9aadd36b2934e9d2025-08-20T02:02:55ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792024-10-018710257610.1016/j.rpth.2024.102576Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIIISylvain Lamoine0Vincent Jury1Virginie Fourneyron2Jonathan Douxfils3Dorian Teissandier4Laurie Talon5Thomas Sinegre6Aurélien Lebreton7Hematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Correspondence Sylvain Lamoine, Hematology Department, University Hospital of Clermont-Ferrand, 1 rue Lucie et Raymond Aubrac, Clermont-Ferrand 63000, France.Hematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, FranceHematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, FranceHematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Department of Pharmacy, Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium; QUALIresearch, QUALIblood s.a., Namur, BelgiumEmergency Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, FranceHematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, FranceHematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, FranceHematology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, FranceBackground: The incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with emicizumab (routine prophylaxis), factor (F)VIII products, and DOAC. Their concomitant presence constitutes a hemostatic challenge. Recent international guidelines stated that data are scarce on the hemostatic balance of plasma samples from patients with HA receiving emicizumab and DOAC. Objectives: The aim of this observational study was to assess the coagulation of FVIII-deficient plasma spiked with DOAC and emicizumab and to evaluate the effects of FVIII addition. Methods: Prothrombin time, activated partial thromboplastin time, and thrombin generation (TG) using the calibrated automated thrombogram method were evaluated in aliquots of a commercial severe HA plasma supplemented with emicizumab (0, 12.5, 25, 50, and 100 ng/mL), DOAC (0, 50, 100, 200, and 400 ng/mL of apixaban, rivaroxaban, edoxaban, or dabigatran) and FVIII (0%, 5%, 15%, 50%, and 100%). Results: DOAC rapidly induced a TG decrease. Emicizumab could counter this effect only for the lowest DOAC dose. FVIII addition to the FVIII-deficient plasma containing a DOAC and emicizumab improved TG and countered the anticoagulant effect of DOAC at ≤100 ng/mL. Conclusion: Our findings indicate that FVIII can be safely used with emicizumab to counter the anticoagulant effect of DOAC at ≤100 ng/mL. The TG assay is an efficient tool to monitor plasma containing anti-FXa DOAC, but not dabigatran (anti-FIIa).http://www.sciencedirect.com/science/article/pii/S2475037924002711direct oral anticoagulantemicizumabhemophilia Amonitoringthrombin |
| spellingShingle | Sylvain Lamoine Vincent Jury Virginie Fourneyron Jonathan Douxfils Dorian Teissandier Laurie Talon Thomas Sinegre Aurélien Lebreton Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII Research and Practice in Thrombosis and Haemostasis direct oral anticoagulant emicizumab hemophilia A monitoring thrombin |
| title | Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII |
| title_full | Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII |
| title_fullStr | Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII |
| title_full_unstemmed | Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII |
| title_short | Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII |
| title_sort | thrombin generation to evaluate the complex hemostatic balance of hemophilia a plasma containing direct oral anticoagulant and supplemented by factor viii |
| topic | direct oral anticoagulant emicizumab hemophilia A monitoring thrombin |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924002711 |
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