Summary of a workshop on potency and dosage of von Willebrand factor concentrates

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

“…Twelve patients with type 3 VWD were administered, in random order, one infusion of either A-SD or A-SD/HT at a dose of 60 VWF:RCof IU/kg, followed in 7 or more days by an identical infusion of the other preparation (median, 109 days; range, 7-186 days). This dosage was chosen because, on the basis of data available from the literature 13 and of pharmacokinetic studies conducted early during this study (data not shown), it was expected that plasma levels would be attained in excess of 100 IU/dL (100% of normal). For each infusion, blood samples for platelet count, plasma levels of VWF:RCof, FVIII:C, and VWF:Ag, and determination of VWF multimeric distribution at a central laboratory (Special Coagulation Laboratory, Pathology Specialty Services, Miami, FL) were obtained at baseline and at 0.25, 1, 3, 6, 12, 24, and 48 hours after infusion.…”

“…Therapy has been largely empirical, not tailored to different VWD types, and it has been based primarily on FVIII for dosing recommendations. 13 Therefore, the main objective of this prospective study was to assess the efficacy of a FVIII/VWF concentrate in patients known not to respond adequately to desmopressin or to have a contraindication to this compound; dosage was based on the content of VWF, the protein missing or dysfunctional in VWD.…”

How I treat patients with von Willebrand disease

“…Because VIII:c in vWD patients has a longer half-life than it does in patients with hemophilia A (24-26 vs 12-14 hours), 18,19 the infusion of one daily dose is sufficient to reach and maintain adequate plasma levels for the treatment of spontaneous bleeding episodes and to prevent excessive bleeding until healing is complete, depending on the site and extent of surgery. Because in the United States the Food and Drug Administration is requiring that plasma products licensed for treatment of vWD patients be labeled in terms of the actual defective protein to be replaced, 28 the solvent-detergent, heat-treated concentrate is labeled in terms of vWF:RCoF content. 19 The doses of this concentrate that I recommend for their demonstrated efficacy in a large, prospective clinical trial are 40 to 60 IU/kg (50-75 IU/kg in children because of the lower in vivo recovery), which usually results in vWF:RCoF plasma levels of 80 to 120 U/dL or higher.…”

Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica

“…1 A doença de von Willebrand (DvW) é a mais freqüente desordem da coagulação, sendo transmitida de forma autossômica dominante. É causada por uma anormalidade quantitativa ou qualitativa do fator de von Willebrand (.vW), que é uma glicoproteína multimérica de alto peso molecular, sintetizada pelas células endoteliais e megacariócitos [2][3][4][5] . As principais funções do .vW são: (a) mediar a interação entre as plaquetas e o colágeno subendotelial; (b) mediar a interação plaqueta-plaqueta, (c) atuar como carreador molecular do .VIII e estabilizador de sua atividade coagulante.…”

“…A deficiência do .vW resulta em alterações das fases primárias e secundárias da coagulação. 2,4,5 A nova classificação pela Sociedade Internacional para Trombose e Hemostasia ISTH identificou 3 tipos principais de DvW: (a) tipo 1 (cerca de 80% dos casos) deficiência parcial quantitativa de .vW; (b) tipo 2 anormalidade qualitativa do .vW com 2 subtipos principais: subtipo 2A com ausência de multímeros de alto peso molecular (HMW), e o subtipo 2B com aumento da afinidade do .vW à glicoproteína plaquetária 1 b e secundária perda de multímeros HMW, usualmente acompanhado de trombocitopenia; (c) tipo 3 deficiência severa de .vW com deficiência secundária de .VIII em vários graus. O padrão familiar não é repetitivo como na hemofilia, variando entre os membros de uma mesma família.…”