Von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease.
Therapy for von Willebrand disease (VWD) aims to restore the hemostatic function conferred by von Willebrand factor (VWF), which facilitates platelet adhesion and aggregation, and serves to increase potentially low coagulation factor VIII (FVIII) in plasma. In patients unresponsive to desmopressin (DDAVP), the preferred treatment is with plasma-derived VWF-containing FVIII concentrates. Only a few of the available VWF/FVIII concentrates have been licensed for use in VWD based on prospective studies. The efficacy of VWF/FVIII concentrates depends on the content and quality of VWF and FVIII. Several studies have demonstrated the variability of the VWF contents, as well as the differences in the VWF multimer patterns (including the high molecular weight VWF multimers that are most effective in restoring hemostasis), among these concentrates. Treating physicians should be aware of these disparities and the potential clinical implications for patients with different VWD subtypes. Dosing has traditionally been calculated based on the FVIII content of the products, although dosing based on VWF functional activity [e.g., VWF ristocetin cofactor activity (VWF:RCo)] addresses the primary protein deficiency in VWD patients. Several clinical studies have demonstrated the efficacy of concentrates dosed according to VWF:RCo. Dosing is generally consistent across VWD subtypes, although patients with severe phenotypes or undergoing major procedures may require more infusions or longer treatment duration. Other considerations for the use of VWF-containing concentrates include laboratory monitoring of efficacy and safety issues such as thrombosis risk and thromboprophylaxis.
Servicio de Hematología y Hemoterapia, Complexo Hospitalario Universitario Juan Canalejo, Departamento de Medicina, Universidad de Santiago de Compostela, A Corunna, Spain. jbatlle@canalejo.org
Javier
J
Batlle
María Fernanda
MF
López-Fernández
Esther Lourés
EL
Fraga
Angela Rodríguez
AR
Trillo
María Almudena
MA
Pérez-Rodríguez
D002986:Clinical Trials as Topic; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D004338:Drug Combinations; D005169:Factor VIII / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors; D014842:von Willebrand Diseases / Q000097:blood / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*
D004338:Drug Combinations; D006490:Hemostatics; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin