title: Management of von Willebrand disease with factor VIII/von Willebrand factor concentrates: results from current studies and surveys.
abstract: Until the mid 1980s, cryoprecipitate had been the mainstay of treatment of patients with von Willebrand disease (VWD) who were unresponsive to desmopressin. The advent of virally inactivated factor VIII/von Willebrand factor (FVIII/VWF) concentrates, originally developed for the treatment of patients with hemophilia, provided improved therapy for VWD. These products were therefore introduced in clinical practice in most European hemophilia centers; one concentrate (Humate-P) was approved for management of VWD in the USA. The 1980s saw the first clinical studies of FVIII/VWF concentrates in patients with VWD, but a standardized procedure for ex vivo effects of these virus-inactivated plasma concentrates in VWD patients became available only in 1992. Study results have shown that the commercially available VWF-containing concentrates are effective in clinical practice (bleeding and surgery), producing responses that may differ depending on the patient's VWD subtype; infusion results in correction of factor VIII activity (FVIII:C) and ristocetin cofactor activity of VWF (VWF:RCo), whereas bleeding time is not consistently corrected. Several studies have demonstrated that FVIII/VWF concentrates have variable VWF multimer patterns relative to normal human plasma. New products should be validated by current methodologies before introduction in clinical practice. Data on several intermediate-purity and high-purity FVIII/VWF concentrates have been reported, and a large prospective study of an intermediate-purity FVIII/VWF concentrate (Haemate P/Humate-P) is currently in progress. In the latter study, for the first time, the appropriate dosage to prevent bleeding during surgery is being calculated on the basis of scheduled pharmacokinetic assessments in each patient. Although thrombotic events are rare in patients with VWD receiving repeated infusions of FVIII/VWF concentrates, there is some concern that sustained high concentrations of FVIII:C may increase the risk of postoperative venous thromboembolism. On the basis of these observations, the dosage and timing of FVIII/VWF administration should be planned to keep FVIII:C concentrations between 50 U/dl and 150 U/dl in the postoperative period.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Dermatology, Fondazione Ospedale Policlinico, Mangiagalli e Regina Elena, and University of Milan, Italy. Augusto.Federici@unimi.it
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Federici
mesh_terms: D016913:Blood Component Transfusion / Q000592:standards; D019468:Disease Management; D005169:Factor VIII / Q000627:therapeutic use*; D006801:Humans; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000628:therapy*; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII