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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(08): 1304-1313
DOI: 10.1055/a-1865-6978
Coagulation and Fibrinolysis

Continuous Infusion of Factor VIII and von Willebrand Factor in Surgery: Trials with pdFVIII LFB or pdVWF LFB in Patients with Bleeding Disorders

Jerzy Windyga
1   Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
,
Benoît Guillet
2   Department of Hemophilia Treatment, CHU Rennes, University of Rennes, Inserm, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France
,
Lucia Rugeri 
3   Hematology Division, Hemophilia Comprehensive Care Center, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, Université Claude Bernard, Lyon, France
,
Alexandra Fournel
4   Hematology Department, CHRU Besançon, France
,
Ewa Stefanska-Windyga
1   Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
,
Valérie Chamouard
3   Hematology Division, Hemophilia Comprehensive Care Center, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, Université Claude Bernard, Lyon, France
,
Sonia Pujol
5   Clinical Development, Laboratoire français du Fractionnement et des Biotechnologies (LFB), Les Ulis, France
,
Céline Henriet 
5   Clinical Development, Laboratoire français du Fractionnement et des Biotechnologies (LFB), Les Ulis, France
,
Françoise Bridey
6   Formerly Clinical Development, LFB, Les Ulis, France
,
Claude Négrier
3   Hematology Division, Hemophilia Comprehensive Care Center, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, Université Claude Bernard, Lyon, France
› Author Affiliations Funding LFB (Les Ulis, France) sponsored the clinical studies presented in this article.
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Abstract

Background A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels.

Aim To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI.

Methods Three phase III trials were conducted. Adults with HA (FVIII:C < 1%) (studies 1 and 2) or VWD (VWF:RCo < 20%) (Study 3) received a preoperative bolus followed by CI of undiluted concentrate for at least 6 days. Bolus doses and CI rates were based on individual recovery and clearance, respectively. The initial infusion rate had to be higher for 48 hours for HA and 24 hours for VWD patients to anticipate potential fluctuations of factor concentrations during major surgery. Target levels of FVIII:C in HA and VWF:RCo in VWD were 80 and 70 IU/dL, respectively. Efficacy was assessed using a global hemostatic efficacy score.

Results Studies 1, 2, and 3 included 12, 4, and 6 patients, respectively. Efficacy outcomes were excellent/good in all 22 major surgeries including 18 orthopedic procedures. Most daily measured FVIII and VWF levels (92%) were on target. No safety concerns, thrombotic events, or inhibitors were identified.

Conclusion pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery.

Keywords

coagulation factor - hemophilia A - von Willebrand disease - surgical procedures

Author Contributions

J.W., C.N., and V.C. contributed in designing the studies, and analyzed and interpreted the data. B.G., L.R., A.F., and E.S.-W. contributed to patient enrolment and collected the data. S.P. and C.H. contributed to the analysis and wrote the manuscript. F.B. designed the studies, interpreted the data, and wrote the manuscript. All authors critically revised the manuscript and approved the final version.


Supplementary Material



Publication History

Received: 20 April 2021

Accepted: 22 December 2021

Accepted Manuscript online:
31 May 2022

Article published online:
24 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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