Outcome of Surgical Interventions in Patients with Haemophilia A and B Treated with Extended Half-Life (EHL) Factor Concentrates in a Single Centre

Abstract

Background

The prevention of intraoperative bleeding in patients with haemophilia is the key to a successful surgical procedure. Daily life of patients with haemophilia A and B significantly improved with prophylaxis with extended half-life factor concentrates (EHL-FVIII and EHL-FIX). The aim of this study was to investigate the efficacy and safety of EHL factor concentrates during surgery.

Methods

In a retrospective chart review all surgical interventions in our hospital in patients with haemophilia A and B treated with EHL-FVIII or EHL-FIX undergoing surgery between 2016 and 2022 were included. Patients with inhibitors against FVIII or FIX were excluded.

Results

A total of 88 surgical interventions (41 minor, 47 major) in 52 patients with haemophilia were performed. The interventions consisted of 70 surgeries in 42 patients with haemophilia A and 18 surgeries in 10 patients with haemophilia B. The replacement therapy during the surgeries was performed with four different EHL FVIII and three different EHL FIX concentrates. Bolus injections were performed directly before surgery and continued after surgery with variable intervals ranging from 8 to 48 hours. The median dose before major surgery was 32.31 IU/kg FVIII and 47.06 IU/kg FIX and before minor surgery was 27.78 IU/kg FVIII and 33.78 IU/kg factor IX. There were 11 complications including 4 bleeding complications during/after surgery. No thromboembolic event and no inhibitor against FVIII or FIX were detected during follow-up.

Summary

The replacement therapy with EHL factor concentrates in surgical interventions in patients with haemophilia A and B is safe and effective.

Keywords

surgery in haemophilia - extended half-life concentrates - haemophilia A and B

Publication History

Received: 05 November 2024

Accepted: 05 May 2025

Article published online:
07 August 2025

• References

• 1 Kerr CB. Operative surgery in haemophilia. Aust N Z J Surg 1964; 33: 241-259
• 2 Mensah PK, Gooding R. Surgery in patients with inherited bleeding disorders. Anaesthesia 2015; 70 (Suppl. 01) 112-120 , e39–e40
• 3 Srivastava A, Santagostino E, Dougall A. et al; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26 (Suppl. 06) 1-158
• 4 Windyga J, Guillet B, Rugeri L. et al. Continuous infusion of factor VIII and von Willebrand factor in surgery: trials with pdFVIII LFB or pdVWF LFB in patients with bleeding disorders. Thromb Haemost 2022; 122 (08) 1304-1313
• 5 National registers of authorised medicines. European Medicines Agency. Accessed at: https://www.ema.europa.eu/en/medicines/national-registers-authorised-medicines
• 6 Mahdi AJ, Obaji SG, Collins PW. Role of enhanced half-life factor VIII and IX in the treatment of haemophilia. Br J Haematol 2015; 169 (06) 768-776
• 7 Lehtinen AE, Baghaei F, Astermark J, Holme PA. Surgical outcomes in patients with haemophilia A or B receiving extended half-life recombinant factor VIII and IX Fc fusion proteins: real-world experience in the Nordic countries. Haemophilia 2022; 28 (05) 713-719
• 8 https://www.ema.europa.eu/en/documents/product-information/elocta-epar-product-information_en.pdf
• 9 https://www.ema.europa.eu/en/documents/product-information/adynovi-epar-product-information_en.pdf
• 10 https://www.ema.europa.eu/en/documents/product-information/jivi-epar-product-information_en.pdf
• 11 https://www.ema.europa.eu/en/documents/product-information/esperoct-epar-product-information_en.pdf
• 12 https://www.ema.europa.eu/en/documents/product-information/idelvion-epar-product-information_en.pdf
• 13 https://www.ema.europa.eu/en/documents/product-information/refixia-epar-product-information_en.pdf
• 14 https://www.ema.europa.eu/en/documents/product-information/alprolix-epar-product-information_en.pdf
• 15 Lison S, Weiss G, Spannagl M, Heindl B. Postoperative changes in procoagulant factors after major surgery. Blood Coagul Fibrinolysis 2011; 22 (03) 190-196
• 16 Coppola A, Windyga J, Tufano A, Yeung C, Di Minno MN. Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery. Cochrane Database Syst Rev 2015; 2015 (02) CD009961
• 17 Mahlangu JN, Ragni M, Gupta N. et al. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A. Thromb Haemost 2016; 116 (01) 1-8
• 18 Powell JS, Josephson NC, Quon D. et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood 2012; 119 (13) 3031-3037
• 19 Solimeno LP, Escobar MA, Krassova S, Seremetis S. Major and minor classifications for surgery in people with hemophilia: a literature review. Clin Appl Thromb Hemost 2018; 24 (04) 549-559
• 20 Small RG, Witt RE. Major and minor surgery. JAMA 1965; 191: 180-182
• 21 Newsome K, McKenny M, Elkbuli A. Major and minor surgery: terms used for hundreds of years that have yet to be defined. Ann Med Surg (Lond) 2021; 66: 102409
• 22 Hermans C, Altisent C, Batorova A. et al; European Haemophilia Therapy Standardisation Board. Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations. Haemophilia 2009; 15 (03) 639-658
• 23 Pavlova A, Oldenburg J. Defining severity of hemophilia: more than factor levels. Semin Thromb Hemost 2013; 39 (07) 702-710
• 24 Levy JH, Dutton RP, Hemphill III JC. et al; Hemostasis Summit Participants. Multidisciplinary approach to the challenge of hemostasis. Anesth Analg 2010; 110 (02) 354-364
• 25 Müller J, Goldmann G, Marquardt N, Pötzsch B, Oldenburg J. Extended half-life factor VIII/factor IX products: assay discrepancies and implications for hemophilia management. Hamostaseologie 2020; 40 (S 01): S15-S20
• 26 Iorio A. Using pharmacokinetics to individualize hemophilia therapy. Hematology (Am Soc Hematol Educ Program) 2017; 2017 (01) 595-604
• 27 Kleiboer B, Layer MA, Cafuir LA. et al. Postoperative bleeding complications in patients with hemophilia undergoing major orthopedic surgery: a prospective multicenter observational study. J Thromb Haemost 2022; 20 (04) 857-865
• 28 Eckhardt CL, van der Bom JG, van der Naald M, Peters M, Kamphuisen PW, Fijnvandraat K. Surgery and inhibitor development in hemophilia A: a systematic review. J Thromb Haemost 2011; 9 (10) 1948-1958
• 29 Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8 (01) 202-204
• 30 Rodriguez-Merchan EC. Surgical wound healing in bleeding disorders. Haemophilia 2012; 18 (04) 487-490
• 31 Monroe DM, Hoffman M. The clotting system—a major player in wound healing. Haemophilia 2012; 18 (Suppl. 05) 11-16
• 32 Sun J, Hua B, Livingston EW. et al. Abnormal joint and bone wound healing in hemophilia mice is improved by extending factor IX activity after hemarthrosis. Blood 2017; 129 (15) 2161-2171
• 33 Hirose J, Takedani H, Nojima M, Koibuchi T. Risk factors for postoperative complications of orthopedic surgery in patients with hemophilia: second report. J Orthop 2018; 15 (02) 558-562
• 34 Ozelo MC. Surgery in patients with hemophilia: is thromboprophylaxis mandatory?. Thromb Res 2012; 130 (Suppl. 01) S23-S26
• 35 Krekeler S, Alesci S, Miesbach W. [Incidence of thromboembolic events after major operations in patients with haemophilia]. Hamostaseologie 2012; 32 (Suppl. 01) S45-S47
• 36 Takedani H, Ohnuma K, Hirose J. Deep venous thrombosis was not detected after total knee arthroplasty in Japanese patients with haemophilia. Haemophilia 2015; 21 (05) 585-588
• 37 Zhang Q, Zhao L, Riva N. et al. Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study. BMC Musculoskelet Disord 2024; 25 (01) 326
• 38 Hermans C. Perioperative thromboprophylaxis in patients with hemophilia and von Willebrand disease undergoing major orthopedic surgery. Paper presented at: Hematology Education: The Education Program for the Annual Congress of the European Hematology Association. 2015 ;9(1): 69-74
• 39 Schutgens REG, Jimenez-Yuste V, Escobar M. et al. Antithrombotic treatment in patients with hemophilia: an EHA-ISTH-EAHAD-ESO clinical practice guidance. HemaSphere 2023; 7 (06) e900
• 40 Santagata D, Abenante A, Squizzato A. et al. Rates of venous thromboembolism and use of thromboprophylaxis after major orthopedic surgery in patients with congenital hemophilia A or B: a systematic review. J Thromb Haemost 2024; 22 (04) 1117-1131