von Willebrand Disease—Therapeutic Options Virally Inactivated FVIII/VWF Concentrates: Antihemophilic Factor/von Willebrand Factor Complex (Human) (Humate-P, Alphanate, Fanhdi)
Mannucci PM. Blood 2001;97:1915–1919
Mannucci PM. N Engl J Med 2004;351:683–694
Indications for FVIII/VWF concentrates:
Demonstration of inadequate response to a test dose of DDAVP (“severe” type 1, type 2, type 3)
Patients in whom DDAVP is contraindicated
Prediction of prolonged treatments with desmopressin (potential or actual tachyphylaxis)
Problem with FVIII/VWF concentrates:
High plasma levels of FVIII are a strong risk factor for venous thrombosis
Venous thrombosis in VWD: 4 cases after treatment with a VWF/FVIII concentrate used to ensure competent hemostasis during invasive and surgical procedures
Venous thromboembolism in VWD: 7 cases in 12,640 yearly treatments over 10 years
Makris M et al. Thromb Haemost 2002;88:387–388
Mannucci PM. Thromb Haemost 2002;88:378–379
Virally Inactivated Antihemophilic Factor/von Willebrand Factor Complex (Human) (FVIII/VWF) Concentrates
Humate-P, Alphanate, and Fanhdi are approved in the United States and in some European countries for use in VWD and are labeled with VWF:RCo units. Ristocetin cofactor units are used to calculate dose (refer to product-specific labeling)
Humate-P (CSL Behring)
Pasteurized
Average VWF:RCo-to-factor VIII ratio: 2.4:1
Efficacy and safety established in 2 prospective and several retrospective studies
Lethagen S et al. J Thromb Haemost 2007;5:1420–1430
Thompson AR et al. Haemophilia 2004;10:42–51
Alphanate (Grifols) and Fanhdi (Grifols)
Virally inactivated by solvent/detergent and heating
VWF:RCo-to-FVIII ratio: varies by product lot (Alphanate)
Efficacy and safety established by 2 prospective studies and a few retrospective studies
Bello IF et al. Haemophilia 2007;13(Suppl 5):25–32
Mannucci PM et al. Blood 2002;99:450–456
Other FVIII/VWF concentrates
Various products, virus-inactivated
Several small retrospective studies
Monitoring Replacement Therapy
Surgical procedures: Measure plasma levels of FVIII and/or VWF:RCo every 12 hours on the day of surgery, then every 24 hours or as dictated by clinical circumstances
It is not usually necessary to monitor replacement therapy in patients with spontaneous minor bleeding
Every physician encounter: Careful clinical follow-up because bleeding may not correlate well with factor levels; careful clinical monitoring is needed