Surgery with emicizumab prophylaxis for two paediatric patients with severe haemophilia A with inhibitors
Corresponding Author
Marguerite Lockhart
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
Correspondence
Marguerite Lockhart, Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Avenue Albert Raimond, 42270 Saint priest en Jarez, France.
Email: [email protected]
Search for more papers by this authorBrigitte Tardy-Poncet
INSERM CIC 1408 Laboratory of Hematology, Saint-Etienne, France
Search for more papers by this authorAurélie Montmartin
Inserm U1059, Sainbiose Dysfonction Vasculaire et Hémostase, Université de Lyon, Saint-Etienne, France
Search for more papers by this authorPauline Noyel
Biology Laboratory University Hospital of Saint-Etienne, Saint-Etienne, France
Search for more papers by this authorSandrine Thouvenin
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
Search for more papers by this authorClaire Berger
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
EA SNA-EPIS 4607, Université Jean Monnet, Saint-Etienne, France
Search for more papers by this authorCorresponding Author
Marguerite Lockhart
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
Correspondence
Marguerite Lockhart, Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Avenue Albert Raimond, 42270 Saint priest en Jarez, France.
Email: [email protected]
Search for more papers by this authorBrigitte Tardy-Poncet
INSERM CIC 1408 Laboratory of Hematology, Saint-Etienne, France
Search for more papers by this authorAurélie Montmartin
Inserm U1059, Sainbiose Dysfonction Vasculaire et Hémostase, Université de Lyon, Saint-Etienne, France
Search for more papers by this authorPauline Noyel
Biology Laboratory University Hospital of Saint-Etienne, Saint-Etienne, France
Search for more papers by this authorSandrine Thouvenin
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
Search for more papers by this authorClaire Berger
Hematology and Oncology Pediatric Unit, Haemophilia CRC Hospital of Saint-Etienne, Saint-Etienne, France
EA SNA-EPIS 4607, Université Jean Monnet, Saint-Etienne, France
Search for more papers by this authorAbstract
Emicizumab is a prophylaxis for patients with severe haemophilia A with and without inhibitor. Despite weekly administration of emicizumab, coagulation states stay below normal value and cannot be assessed by standard haemostasis tests. In our two patients, we used the thrombin-generation assay (endogenous thrombin potential and Peak) to monitor the patient's clotting status. Under emicizumab, it is necessary to add a bypassing agent (BPA) such as rFVIIa (Novoseven) to avoid bleeding before surgery. The BPA dosage was based on a thrombin-generation assay and collegial consultation.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
REFERENCES
- 1Mannucci PM, Tuddenham EGD. The hemophilias — from royal genes to gene therapy. N Engl J Med. 2001; 344: 1773-1779.
- 2Baglin T. The measurement and application of thrombin generation. Br J Haematol. 2005; 130: 653-661.
- 3Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol. 2004; 127: 379-391.
- 4Owaidah T, Momen AA, Alzahrani H, et al. The prevalence of factor VIII and IX inhibitors among Saudi patients with hemophilia: Results from the Saudi national hemophilia screening program. Medicine (Baltimore). 2017; 96:e5456.
- 5Aledort L, Ljung R, Mann K, Pipe S. Factor VIII therapy for hemophilia A: current and future issues. Expert Rev Hematol. 2014; 7: 373-385.
- 6Scott LJ, Kim ES. Emicizumab-kxwh: first global approval. Drugs. 2018; 78: 269-274.
- 7Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017; 377: 809-818.
- 8Barg AA, et al. Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors—a single-center cohort. Pediatr Blood Cancer. 2019; 66:e27886.
- 9Nogami K. Bispecific antibody mimicking factor VIII. Thromb Res. 2016; 141: S34-S35.
- 10Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A with inhibitors. N Engl J Med. 2018; 379: 811-822.
- 11Le Quellec S. Clinical evidence and safety profile of emicizumab for the management of children with hemophilia A. Drug Des Devel Ther. 2020; 14: 469-481.
- 12Young G, Sidonio RF, Liesner R, et al. HAVEN 2 updated analysis: multicenter, open-label, phase 3 study to evaluate efficacy, safety and pharmacokinetics of subcutaneous administration of emicizumab prophylaxis in pediatric patients with hemophilia A with inhibitors. Blood. 2017; 130: 85.
- 13Dargaud Y, Lambert T, Trossaert M. New advances in the therapeutic and laboratory management of patients with haemophilia and inhibitors. Haemophilia. 2008; 14: 20-27.
- 14Dargaud Y, Lienhart A, Negrier C. Prospective assessment of thrombin generation test for dose monitoring of bypassing therapy in hemophilia patients with inhibitors undergoing elective surgery. Blood. 2010; 116: 5734-5737.
- 15Dargaud Y, Lienhart A, Janbain M, Le Quellec S, Enjolras N, Negrier C. Use of thrombin generation assay to personalize treatment of breakthrough bleeds in a patient with hemophilia and inhibitors receiving prophylaxis with emicizumab. Haematologica. 2018; 103: e181-e183.
- 16Mathieu S, Crampe C, Dargaud Y, et al. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test. Blood Coagul Fibrinolysis. 2015; 26: 940-945.
- 17Barg AA, Livnat T, Budnik I, et al. Emicizumab treatment and monitoring in a paediatric cohort: real-world data. Br J Haematol. 2020; 191: 282-290.
- 18Coppola A, Di Capua M, Di Minno MN, et al. Treatment of hemophilia: a review of current advances and ongoing issues. J Blood Med. 2010; 1: 183-195.
- 19Hoffman M, Dargaud Y. Mechanisms and monitoring of bypassing agent therapy. J Thromb Haemost. 2012; 10: 1478-1485.
- 20 New Drug: Emicizumab for Haemophilia A. Aust. Prescr. 2019; 42: 29.
- 21Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019; 25: 979-987.
- 22Oldenburg J, Mahlangu JN, Bujan W, et al. The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 study. Haemophilia. 2019; 25: 33-44.
- 23Hartmann R, Feenstra T, Valentino L, Dockal M, Scheiflinger F. In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents. J Thromb Haemost. 2018; 16: 1580-1591.
- 24Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017; 377: 809-818.
- 25Kruse-Jarres R, Callaghan MU, Croteau SE, et al. Surgical experience in two multicenter, open-label phase 3 studies of emicizumab in persons with hemophilia A with inhibitors (HAVEN 1 and HAVEN 2). Blood. 2017; 130: 89.
- 26Kizilocak H, Marquez-Casas E, Phei Wee C, Malvar J, Carmona R, Young G. Comparison of bypassing agents in patients on emicizumab using global hemostasis assays. Haemophilia. 2021; 27: 164-172.
- 27Dargaud Y, Lienhart A, Meunier S, et al. Major surgery in a severe haemophilia A patient with high titre inhibitor: use of the thrombin generation test in the therapeutic decision. Haemophilia. 2005; 11: 552-558.
- 28Srivastava Y, Chandy M, Sunderaj GD, et al. Low-dose intermittent factor replacement for post-operative haemostasis in haemophilia. Haemophilia. 1998; 4: 799-801.
- 29Kizilocak H, Yukhtman CL, Marquez-Casas E, Lee J, Donkin J, Young G. Management of perioperative hemostasis in a severe hemophilia A patient with inhibitors on emicizumab using global hemostasis assays. Ther Adv Hematol. 2019; 10:2040620719860025.
- 30Santagostino E, Oldenburg J, Chang T, et al. Surgical Experience from Four Phase III Studies (Haven 1–4) of Emicizumab in Persons with Haemophilia A (PwHA) With or Without FVIII Inhibitors. Res Pract Thromb Haemost. 2019; suppl 1(3):116
