Differential effect of the ABO blood group on von Willebrand factor collagen binding activity and ristocetin cofactor assay

SummaryFive plasma preparations (11 lots) used in the treatment of von Willebrand’s disease (vWD) were evaluated. The collagen binding function of von Willebrand factor (vWF) containing preparations was compared with the ristocetin cofactor activity and the vWF antigen. Some preparations have higher ratio of functional activity (ristocetin cofactor and collagen binding) relative to the antigen than is found in normal plasma. The ristocetin cofactor activity and the collagen binding activity are tightly correlated (r = .95). Ultracentrifugal (UCF) analysis was used to compare the size distribution of vWf antigen, ristocetin cofactor and collagen binding activity. The sedimentation of all of the vWF parameters in the plasma products was slower than in plasma. In plasma products the ristocetin cofactor activity sediments the most rapidly, the collagen binding activity is slower and the antigen the slowest. The collagen/antigen ratio decreases with decreasing vWF size. Assignment of potency to vWF containing preparations utilizing the collagen binding activity may be more precise and as accurate as with the traditional ristocetin cofactor assay.

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Effect of ABO blood group on the collagen-binding assay for von Willebrand factor

American Journal of Hematology ◽

10.1002/ajh.10238 ◽

2002 ◽

Vol 71 (3) ◽

pp. 229-231 ◽

Cited By ~ 6

Author(s):

Erin Haley ◽

Nadiya Babar ◽

Cory Ritter ◽

Katharine A. Downes ◽

Deana Green ◽

...

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Binding Assay ◽

Abo Blood Group ◽

Collagen Binding ◽

Von Willebrand ◽

Willebrand Factor

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Effect of von Willebrand factor Y/C1584 on in vivo protein level and function and interaction with ABO blood group

Blood ◽

10.1182/blood-2006-07-035105 ◽

2006 ◽

Vol 109 (7) ◽

pp. 2840-2846 ◽

Cited By ~ 25

Author(s):

James Anthony Davies ◽

Peter William Collins ◽

Lee Sarah Hathaway ◽

Derrick John Bowen

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Qualitative Difference ◽

Binding Activity ◽

Abo Blood Group ◽

Entire Cohort ◽

And Function ◽

Von Willebrand ◽

Willebrand Factor

Abstract Blood group O and the cysteine allele of the Y/C1584 change in von Willebrand factor (VWF) are enriched in type 1 VWD, but neither causes disease. We investigated the effect of C1584, alone and in combination with the ABO blood group, on the level and properties of plasma VWF. A cohort of 5052 blood donors was recruited: 50 donors were heterozygous for Y/C1584 and 5002 were homozygous for Y/Y1584. Mean VWF antigen (VWF:Ag) for heterozygotes (82 ± 35 IUdL−1) was significantly lower than for homozygotes (111 ± 37 IUdL−1) (P < .001). For each ABO blood group, VWF:Ag was decreased among Y/C1584 heterozygotes compared with Y/Y1584 homozygotes; a larger decrease was observed for group O. Among donors with VWF:Ag levels of 50 IUdL−1 or lower, Y/C1584 heterozygosity was markedly enriched (18%) compared with the entire cohort (1.5%). Blood group O was enriched to a lesser extent (2.4%), but Y/C1584 in conjunction with group O was strikingly enriched (34.8%). VWF collagen binding activity (VWF:CB) and ristocetin cofactor activity (VWF:RCo) were significantly lower for Y/C1584 heterozygotes than for Y/Y1584 homozygotes, and a qualitative difference in Y/C1584 plasma VWF multimer profile was observed compared with that for Y/Y1584 VWF. The data support a multifactorial basis for low VWF levels in some individuals.

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Collagen Binding Assay for von Willebrand Factor (VWF:CBA): Detection of von Willebrands Disease (VWD), and Discrimination of VWD Subtypes, Depends on Collagen Source

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613768 ◽

2000 ◽

Vol 83 (01) ◽

pp. 127-135 ◽

Cited By ~ 92

Author(s):

Emmanuel Favaloro

Keyword(s):

Von Willebrand Factor ◽

Binding Activity ◽

Type Iii Collagen ◽

Type I ◽

Collagen Concentration ◽

Collagen Binding ◽

Type Iii ◽

Von Willebrand ◽

Willebrand Factor ◽

Ristocetin Cofactor

SummaryA large number of different collagen preparations [n = 21] have been assessed for their ability to both detect von Willebrands Disease (VWD), and discriminate different VWD subtypes. Collagen preparations were tested at a range of concentrations and included: Type I, III and IV, and various mixtures of these, as aqueous supplied preparations and/or reconstituted from bulk lyophilised stock. Tissue sources for collagens ranged from human placenta to calf skin to equine tendon. Three of the collagen preparations tested did not support von Willebrand factor (VWF) binding in an ELISA process (therefore unable to detect VWD). The ability of the remaining preparations to detect VWF was variable, as was their ability to discriminate VWD subtypes. Detection of VWF and discrimination of VWD subtypes was not mutually inclusive. Thus, some collagen preparations provided excellent detection systems for VWF, but comparatively poorer discrimination of Type 2 VWD, while others provided good to acceptable detection and discrimination. Subtype discrimination was also dependent on the collagen concentration, and some batch to batch variation was evident with some preparations (particularly Type I collagens). Overall, best discrimination was typically achieved with Type I/III collagen mixtures, or Type III collagen preparations (where effectiveness was highly dependent on concentration). Good discrimination was also achieved with a commercial Type III collagen based VWF:CBA kit method. Results of the various ‘VWF:CBA assays’ are also compared with those using the Ristocetin Cofactor (VWF:RCof) assay (by platelet agglutination) and that using a commercial ‘VWF:RCof-alternative/ activity’ ELISA procedure. These latter methodologies tended to be less sensitive to VWF-discordance when compared to that detected by the majority of the VWF:CBA procedures. Abbreviations: FVIII:C Factor VIII: coagulant (assay); HMW High Molecular Weight [VWF]; PNP Pooled Normal Plasma; RIPA Ristocetin induced platelet aggregation procedure; VWD von Willebrands disease; VWF von Willebrand Factor; VWF:Ag von Willebrand Factor Antigen (assay); VWF: CBA Collagen Binding [Activity] Assay for VWF; VWF:RCof Ristocetin Cofactor Assay for VWF

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Decreased half-life time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: normalization after cytoreduction of the increased platelet count

British Journal of Haematology ◽

10.1046/j.1365-2141.1997.4823285.x ◽

1997 ◽

Vol 99 (4) ◽

pp. 832-836 ◽

Cited By ~ 36

Author(s):

Perry J. J Van Genderen ◽

Fransisco J Prins ◽

Irene S. Lucas ◽

Desiree Van De Moesdijk ◽

Huub H. D. M. Van Vliet ◽

...

Keyword(s):

Platelet Count ◽

Von Willebrand Factor ◽

Half Life ◽

Life Time ◽

Binding Activity ◽

Essential Thrombocythaemia ◽

Collagen Binding ◽

Von Willebrand ◽

Willebrand Factor

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ABO blood group also influences the von Willebrand factor (VWF) antigen level in heterozygous carriers of VWF null alleles, type 2N mutation Arg854Gln, and the missense mutation Cys2362Phe

Blood ◽

10.1182/blood-2002-04-1168 ◽

2002 ◽

Vol 100 (5) ◽

pp. 1927-1928 ◽

Cited By ~ 14

Author(s):

Giancarlo Castaman ◽

Jeroen C. J. Eikenboom

Keyword(s):

Missense Mutation ◽

Blood Group ◽

Von Willebrand Factor ◽

Null Alleles ◽

Abo Blood Group ◽

Antigen Level ◽

Heterozygous Carriers ◽

Von Willebrand ◽

Willebrand Factor

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Standardization and comparison of nonautomated assays to measure the collagen binding activity of von Willebrand factor

International Journal of Laboratory Hematology ◽

10.1111/ijlh.12874 ◽

2018 ◽

Vol 40 (5) ◽

pp. 597-603 ◽

Cited By ~ 1

Author(s):

L. M. M. Oliveira ◽

M. V. A. Amorim ◽

C. A. Corsini ◽

C. C. A. Neto ◽

D. G. Chaves

Keyword(s):

Von Willebrand Factor ◽

Binding Activity ◽

Collagen Binding ◽

Von Willebrand ◽

Willebrand Factor

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Genetic determinants of VWF clearance and FVIII binding modify FVIII pharmacokinetics in pediatric hemophilia A patients

Blood ◽

10.1182/blood.2019000190 ◽

2019 ◽

Vol 134 (11) ◽

pp. 880-891 ◽

Cited By ~ 7

Author(s):

Laura L. Swystun ◽

Kenichi Ogiwara ◽

Orla Rawley ◽

Christine Brown ◽

Ilinca Georgescu ◽

...

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Half Life ◽

Hemophilia A ◽

Blood Type ◽

Abo Blood Group ◽

Genetic Determinants ◽

Group Status ◽

Von Willebrand ◽

Willebrand Factor

Abstract Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.

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