A Very‐High‐Purity von Willebrand Factor Preparation Containing High‐Molecular‐Weight Multimers

Barington, Karina A.; Kaersgaard, P.

doi:10.1046/j.1423-0410.1999.7620085.x

Cited by 7 publications

(9 citation statements)

References 13 publications

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“…38,[66][67][68] More recent work with both factor concentrates and recombinant vWF has increased interest. 43,45,49,51,[69][70][71] Nevertheless, there has been some reluctance in universal acceptance by the general blood banking and concentrate therapy community, possibly because of standardization issues. For example, the Food and Drug Administration (FDA) is still to approve the vWF:CBA (and the vWF:RCof ) as vWF activity assays for the purpose of vWD diagnosis and concentrate analysis because of lack of standardization.…”

Section: The Vwf:cba-a Historical Perspectivementioning

confidence: 99%

von Willebrand Factor Collagen-Binding (Activity) Assay in the Diagnosis of von Willebrand Disease: A 15-Year Journey

Favaloro¹

2002

Semin Thromb Hemost

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The correct diagnosis and classification of von Willebrand disease (vWD) is crucial because the presenting biological activity of von Willebrand factor (vWF) determines both the hemorrhagic risk and the subsequent clinical management. A variety of laboratory assays may be employed, not necessarily restricted to assessments of vWF. This article discusses the relative strengths and limitations of various functional or discriminatory vWF assays with a special focus on the vWF:collagen-binding activity (vWF:CBA) assay. This is a functional vWF assay that relies on the property of vWF adhesion to collagen. The vWF:CBA was first described approximately 15 years ago. The journey from that time point has been an interesting one, and the vWF:CBA is now gaining more widespread acceptance. There are now many published studies confirming the superiority of the vWF:CBA over the vWF ristocetin cofactor (vWF:RCof) activity as a functional screening diagnostic test process for vWD. However, both tests may be required in order to appropriately diagnose all forms of vWD. The relationship of these assays with multimer analysis is also discussed. In summary, an optimized vWF:CBA detects primarily high-molecular-weight (HMW) vWF forms and probably only about 30% of the total plasma vWF pool detected by vWF antigen (vWF:Ag). Because these HMW vWF forms are missing in types 2A and 2B vWD, the vWF:CBA is extremely useful in the detection of these qualitative vWD subtypes. In addition, however, concordance of vWF:CBA with vWF:Ag in unison with low vWF levels may alternatively suggest a type 1 vWD, and an absence of both vWF:Ag and vWF:CBA will suggest type 3 vWD. The vWF:CBA is also being investigated in various disease states, as is its usefulness as an effective marker of functional HMW vWF in both desmopressin (DDAVP) and factor-concentrate therapy in vWD.

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Section: The Vwf:cba-a Historical Perspectivementioning

confidence: 99%

von Willebrand Factor Collagen-Binding (Activity) Assay in the Diagnosis of von Willebrand Disease: A 15-Year Journey

Favaloro¹

2002

Semin Thromb Hemost

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“…Most commercial factor concentrates currently utilise VWF:RCo to assess VWF function in comparison with VWF:Ag (e. g. [19][20][21][22][23][24][25][26][27][28][29][30][31]. VWF:CB has been previously tested with factor concentrates in a limited number of studies (9,11,14,15,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), most of which assessed pre-commercial factor preparations. Such pre-commercial studies largely confirm retention of VWF:CB according to retention of HMW VWF (e. g. 11,14,38,39).…”

Section: Discussionmentioning

confidence: 99%

A Comparative Multi-laboratory Assessment of Three Factor VIII/von Willebrand Factor Concentrates

Favaloro¹,

Bukuya²,

Martinelli³

et al. 2002

Thromb Haemost

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SummaryFive expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; X3), Biostate® (X3) and Humate/Haemate (X3). All laboratories blind tested for FVIII:C, VWF:Ag and VWF:CB, four tested for VWF:RCo, and one performed VWF:Multimers. The study yielded inter-laboratory CVs for VWF:Ag and FVIII:C around 10–15%, and for VWF:CB and VWF:RCo around 20%, significantly lower than those of previous multi-laboratory surveys. All three lots of AHF HP contained in the vicinity of 25 U/ml FVIII:C, around 60–75 U/ml of VWF:Ag, but only 30–45 U/ml of VWF:CB and 40–50 U/ml of VWF:RCo (thus, CB/Ag ratio around 0.5–0.6 and RCo/Ag ratio around 0.6–0.7). Study determined that FVIII:C and VWF:RCo levels were similar to manufacturer assigned levels. Some loss of the high molecular weight (HMW) multimers was observed, together with an intense low molecular weight (LMW) VWF band consistent with some reduction or proteolysis of HMW VWF. All three lots of Humate/Haemate contained in the vicinity of 23–32 U/ml of FVIII:C, 70–105 U/ml of VWF:Ag, 50–90 U/ml of VWF:CB and VWF:RCo (i. e. CB/Ag ratio around 0.6–0.9 and RCo/Ag ratio around 0.6–1.1). Study-determined FVIII:C and VWF:RCo levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was also observed with Humate/Haemate. All three lots of Biostate contained in the vicinity of 40–55 U/ml of FVIII:C, 105–170 U/ml of VWF:Ag, 90–150 U/ml of VWF:CB, and 90–135 U/ml of VWF:RCo (i. e. CB/Ag and RCo/Ag ratios around 0.7–1.0). Study-determined FVIII:C levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was not observed with Biostate. The defined pattern of increasing CB/ Ag from AHF HP to Humate/Haemate and Biostate was consistently observed in study data from each of the five laboratories. In conclusion, study findings indicate some differences in the retention of functional/ HMW VWF between factor concentrates, and this is expected to have significant implications in terms of clinical efficacy for therapy in VWD.

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“…This is evidenced by the standard for WorkBeads 40S yield of proteins complex (75.4 ± 5.2 for S/D treatment, p>0.5) and its specific activity (13.4 ± 0.3 IU/mg complex for S/D treatment, p>0.2). Moreover, both the specific activity of FVIII:C at the stage of cation exchange chromatography and the yield of protein at a single chromatographic stage are quite typical for the purification process of coagulation FVIII/vWF complex [47,48].…”

Section: Target Protein Yield and Activity After In-column Treatmentmentioning

confidence: 99%

The Simultaneous Human FVIII/vWF Purification and Virus Inactivation Combined in Chromatographic Column

Volkov¹

2017

J Biomol Res Ther

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A Very‐High‐Purity von Willebrand Factor Preparation Containing High‐Molecular‐Weight Multimers

Abstract: Very-high-purity, double virus-inactivated vWf preparations containing high molecular weight multimers were obtained on a production scale.

Cited by 7 publications

References 13 publications

von Willebrand Factor Collagen-Binding (Activity) Assay in the Diagnosis of von Willebrand Disease: A 15-Year Journey

von Willebrand Factor Collagen-Binding (Activity) Assay in the Diagnosis of von Willebrand Disease: A 15-Year Journey

A Comparative Multi-laboratory Assessment of Three Factor VIII/von Willebrand Factor Concentrates

The Simultaneous Human FVIII/vWF Purification and Virus Inactivation Combined in Chromatographic Column

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