Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis

Abstract

In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.1% of the corresponding bands in normal human plasma. Use of this multimer analysis method for the characterization of five further commercial products revealed clear differences with respect to the high molecular weight vWF multimer content. Furthermore, there is a linear correlation (r2 = 0.73) between the content of high molecular weight vWF multimers and the specific activity of vWF (determined as vWF:RCoF/vWF:Ag). The method described here for analysis of the content of high molecular weight vWF multimers is a reliable and reproducible method to characterize this class of factor concentrates with respect to vWF multimer composition.

Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial

“…The ULMW multimers present in vivo are, however, transient, due to rapid proteolysis of the multimers by the plasma metalloprotease ADAMTS13. 5,[33][34][35] Proteolysis by ADAMTS13 occurs on endothelial cell membranes after VWF release from Weibel-Palade bodies, as well as in the plasma. 36 In pdVWF concentrates, the quantity of the larger, most hemostatically active multimers of VWF is decreased compared with human plasma as a result of prior exposure to ADAMTS13.…”

Clinical use of Haemate(R) P in inherited von Willebrand's disease: a cohort study on 100 Italian patients

“…Patients received 5.60×10 6 IU VWF:RCo in 1,424 infusions of Haemate ® P given three times (53.0%) or twice (47.0%) a week, with clinical responses rated as excellent/good response in 100%. Among patients receiving prophylaxis, 70% had VWD type 3 and received 54% of the overall product infused (Table 4).…”

“…5 Haemate ® P/Humate ® P, a pasteurized plasma-derived VWF/FVIII concentrate widely used in VWD, is characterized by a very high content of VWF (VWF:RCo IU, 2.4 for each IU of FVIII:C) with a relatively high percentage of large molecular weight VWF multimers. [6][7][8] Haemate ® P has also had an excellent safety record with regards to blood-borne infections over the past 25 years of clinical use. [9][10][11][12] Clinical efficacy data were collected for Haemate ® P through a large retrospective study organized by the Canadian Hemophilia Centers.…”

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

“…Nos pacientes do estudo foi usado o 8Y em uma paciente com o tipo 1 da doença, ao invés do DDAVP, devido ao longo tempo cirúrgico, intensidade da perda sangüínea trans-operatória e extensão da doença tumoral, tendo sido inclusive necessária a ressecção parcial de dura-máter e reconstrução da mesma e da base anterior do crânio e na criança de 2 anos com o tipo 3 da doença. 6,13,16,20,21 Em uma paciente com deficiência grave de fator X foi usado o complexo protrombínico (PPSB). O PPSB é um derivado plasmático que contém os fatores II, VII, IX e X, e proteínas C e S. É usado no tratamento de reposição da hemofilia B e nas demais deficiências.…”