Evolution of replacement therapy for von Willebrand disease: From plasma fraction to recombinant von Willebrand factor

Authors: Peyvandi F, Kouides P, Turecek PL, Dow E, and Berntorp E.

Publication: Blood Reviews, May 2020

Affiliations: Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Dept Pathophysiol & Transplantat, Via Pace 9, I-20122 Milan, Italy; Univ Rochester, Sch Med, Mary M Gooley Hemophilia Ctr Inc, Rochester, NY USA; Baxalta Innovat GmbH, Vienna, Austria; Norfolk Ctr Canc Care & Hematol, Brockton, MA USA ; Lund Univ, Ctr Thrombosis & Hemostasis, Malmo, Sweden.

Abstract: The diagnosis and treatment of von Willebrand disease (VWD) are challenging, in part because patients exhibit a wide range of bleeding patterns and manifestations (e.g. epistaxis, gingival bleeding, heavy menstrual bleeding, gastrointestinal bleeds, postoperative bleeding, hemarthroses) and in part because many tests are required to make an accurate diagnosis. Factor replacement therapies for VWD are the mainstay of treatment for patients who do not respond to desmopressin. They have gradually evolved from crude preparations of plasma proteins to plasma-derived concentrates containing both von Willebrand factor (VWF) and factor VIII (FVIII). However, varying amounts and quality of VWF and varying content of FVIII have contributed to the lack of a standardized approach to replacement therapy. More recently, the treatment of VWD has undergone a slow yet significant change from plasma-derived VWF/FVIII concentrates with VWF:ristocetin cofactor (RCo)/FVIII ratios <= 1, to those with VWF:RCo/FVIII ratios > 10, to a recombinant VWF. This article reviews the evolution of factor replacement therapy for patients with VWD that has occurred over the last several decades. The availability of a greater variety of factor replacement therapies poses a challenge in terms of a standard algorithm of care but may help overcome the limitations of earlier treatments and allow treatment personalization according to individual patient needs.