Replacement Therapy with Virus—Inactivated Plasma Concentrates in von Willebrand Disease

Abstract

In von Willebrand disease, the goal of treatment is to correct the two laboratory hallmarks of abnormal hemostasis, i.e. the deficiency of factor VIII (FVIII) and the prolonged bleeding time (BT). Since desmopressin (DDAVP) is able to achieve both these goals in the majority of patients, it is the treatment of choice. Some patients, however, are not responsive or become refractory to DDAVP. In these, blood products maintain an important therapeutic role, and there is a need to assess the efficacy of the recently available virus-inactivated plasma concentrates, which contain both FVIII and von Willebrand factor and carry a low risk of transmitting blood-borne viruses. Our survey of the data reported in the literature indicates that all available concentrates are similarly effective in attaining high and sustained levels of FVIII after infusion. Although they often shorten or normalize the prolonged BT, that effect is less uniform. Since concentrates appear efficacious in the majority of clinical situations that require the use of blood products, they should be preferred, because of their greater safety, to cryoprecipitate produced by blood banks, which cannot be virus inactivated.

How I treat patients with von Willebrand disease

“…Therefore, virus-inactivated VIII-vWF concentrates, originally developed for the treatment of hemophilia A, are perceived as safer and are preferred in the management of patients with vWD unresponsive to desmopressin. 17 Two commercially available concentrates have been evaluated more extensively than others, and clinical studies have demonstrated their efficacy in preventing or stopping bleeding. 18,19 One, licensed in the United States and in several European countries for the treatment of vWD, contains relatively larger amounts of VIII:c than of vWF measured as vWF:RCoF (approximately 2-3 times more in terms of IU).…”

Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study

“…6 Thus, in 20% to 30% of patients, the replacement of VWF and FVIII with plasma-derived concentrates is the mainstay of treatment. 7 Cryoprecipitate, derived from fresh-frozen plasma thawed at 4°C, is no longer considered the optimal replacement because of the risk for transfusion-associated viral infection and the inconvenience of storage and preparation for use. Virally attenuated plasma-derived FVIII/VWF concentrates, originally developed for the treatment of hemophilia A, are used in desmopressinunresponsive patients.…”

Unexpected Bleeding Disorders

“…In some situations, such as post-operatively and in the presence of soft tissue hemorrhage, it appears that correcting factor VIII deficiency is more important than correcting vWF. 40 However, much of the experience leading to this conclusion was gained using products containing both factor VIII and vWF, and the latter was generally monitored by the skin bleeding time, which is no longer accepted as a valid marker of the therapeutic response. If one's treatment aim is to maintain factor VIII levels, less frequent dosing with VIII/vWF concentrates (typically once a day) will be needed, because of the prolonged half-life of factor VIII in vWD patients.…”