Subscribe to RSS
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/s-0039-3401001
Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors
Funding This research was supported by a research grant from Chugai Pharmaceutical Co. Ltd. H.K. has received honoraria from Bristol-Myers Squibb and research funding from Kyowa Hakko Kirin Co. Ltd., Zenyaku Kogyo, Fujifilm Corporation, Nippon Shinyaku Co. Ltd., Eizai Co. Ltd., Pfizer Inc., Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Celgene Corporation, Otsuka Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., and Sanofi K.K.Publication History
22 August 2019
25 October 2019
Publication Date:
05 December 2019 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00033990/201904/lookinside/thumbnails/10-1055-s-0039-3401001_190044cr-1.jpg)
Abstract
We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors.
-
References
- 1 Collins PW, Chalmers E, Hart DP. , et al. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia (4th ed.). UK Haemophilia Centre Doctors Organization. Br J Haematol 2013; 160 (02) 153-170
- 2 Mingot-Castellano ME, Álvarez-Román MT, López-Fernández MF. , et al. Spanish consensus guidelines on prophylaxis with bypassing agents for surgery in patients with haemophilia and inhibitors. Eur J Haematol 2016; 96 (05) 461-474
- 3 Srivastava A, Brewer AK, Mauser-Bunschoten EP. , et al; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (01) e1-e47
- 4 Dimichele DM. Management of factor VIII inhibitors. Int J Hematol 2006; 83 (02) 119-125
- 5 Kitazawa T, Igawa T, Sampei Z. , et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med 2012; 18 (10) 1570-1574
- 6 Yoneyama K, Schmitt C, Kotani N. , et al. A pharmacometric approach to substitute for a conventional dose-finding study in rare diseases: example of phase III dose selection for emicizumab in hemophilia A. Clin Pharmacokinet 2018; 57 (09) 1123-1134
- 7 Nogami K, Soeda T, Matsumoto T, Kawabe Y, Kitazawa T, Shima M. Routine measurements of factor VIII activity and inhibitor titer in the presence of emicizumab utilizing anti-idiotype monoclonal antibodies. J Thromb Haemost 2018; 16 (07) 1383-1390
- 8 Yada K, Nogami K, Ogiwara K. , et al. Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis. Int J Hematol 2019; 110 (04) 419-430