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KMID : 0043320200430070714
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Archives of Pharmacal Research
2020 Volume.43 No. 7 p.714 ~ p.723
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Characterization of the von Willebrand factor/factor VIII complex produced by a novel purification process
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Ahn Jee-Won
Chang Eun-Sun
Jung You-Jin
Kim So-Ra
Seong Baik L.
Ha Suk-Hoon
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Abstract
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Factor VIII (FVIII) is a blood coagulation protein that circulates as a complex with von Willebrand factor (vWF) in the plasma. In the survey of inhibitors in plasma product exposed toddlers (SIPPET) study, plasma-derived FVIII containing vWF was less immunogenic in hemophilia A patients than products with only high-purity FVIII only or recombinant FVIII. The FVIII purified by the conventional purification process using anion-exchange (AEX) chromatography had a low vWF content. In this study, purified vWF was added to the purified FVIII to increase the vWF content. The purified vWF was recovered from the discarded washing solution of the AEX chromatography using cation-exchange (CEX) chromatography. The vWF/FVIII complex had an abundance of high molecular weight vWF similar to the normal plasma, and a low reactivity of FVIII inhibitors. Furthermore, its efficacy was observed in a mouse model of hemophilia A. Therefore, the vWF/FVIII complex produced by our new purification method could be an effective and less immunogenic therapeutic agent for the hemophilia A and von Willebrand disease.
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KEYWORD
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Factor VIII, von Willebrand factor, Hemophilia A, von Willebrand disease
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