scholarly journals von Willebrand factor: evidence for variable clearance in vivo according to Y/C1584 phenotype and ABO blood group

2007 ◽  
Vol 6 (1) ◽  
pp. 97-103 ◽  
Author(s):  
J. A. DAVIES ◽  
P. W. COLLINS ◽  
L. S. HATHAWAY ◽  
D. J. BOWEN
Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2840-2846 ◽  
Author(s):  
James Anthony Davies ◽  
Peter William Collins ◽  
Lee Sarah Hathaway ◽  
Derrick John Bowen

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.


Blood ◽  
2019 ◽  
Vol 134 (11) ◽  
pp. 880-891 ◽  
Author(s):  
Laura L. Swystun ◽  
Kenichi Ogiwara ◽  
Orla Rawley ◽  
Christine Brown ◽  
Ilinca Georgescu ◽  
...  

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.


Vox Sanguinis ◽  
1995 ◽  
Vol 68 (4) ◽  
pp. 236-240 ◽  
Author(s):  
Masayuki Shima ◽  
Yoshihiro Fujimura ◽  
Takayuki Nishiyama ◽  
Tomomi Tsujiuchi ◽  
Nobuhiro Narita ◽  
...  

2002 ◽  
Vol 71 (3) ◽  
pp. 229-231 ◽  
Author(s):  
Erin Haley ◽  
Nadiya Babar ◽  
Cory Ritter ◽  
Katharine A. Downes ◽  
Deana Green ◽  
...  

1987 ◽  
Author(s):  
F Rodeghiero ◽  
G Castaman ◽  
E Di Bona ◽  
M Ruggeri

Bleeding time (BT) is the most important test for in "vivo" Vevaluation of primary hemostasis. Several physiological parameters namely sex, age, blood group, hematocrit, platelet count and von Willebrand factor level could exert a significant influenceIn this study, the relationships between BT (Simplate II,General Diagnostics)and these physiological parameters havebeen examined in 58 subjects aging 17-71 (32 males and 26 females; 26 of 0 and 32 of non-0 group). In all the subjects bleedingdiathesis was excluded by interview. They were not taking anvmedicament for at least 10 days and showed normal platelet aggregation by ADP and ArachidonateMean BT value (seconds) was 318± 65 (range 195-A95)Statistical analysis failed to show any significant difference realated to sex and blood group. There was no significant relationship with hematocrit (0.01), platelet count (−0.2A), age (−0.28) and von Willebrand factor level, mesured as ristocetin cofactor (−0.2A). In particular, our data indicate that higher von Willebrand factor levels found in non-0 group in comparison with O-group (113.3 vs 83.5, P < 0:001) do not exert any apparent influence on bleeding time


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4024-4024
Author(s):  
Maria Lourdes Barjas Castro ◽  
Aline Crucello ◽  
Heloise P. Fernandes ◽  
Norma C. Sousa ◽  
Joyce M. Annichino-Bizzacchi ◽  
...  

Abstract ABO blood group has been described to influence levels of von Willebrand factor (VWF), as well as factor VIII. Individuals carrying O allele have significant lower plasma levels of these factors. Indeed, recently non-O individuals have been described to have increased risk for both, arterial and venous thrombotic disease. VWF mediate platelet interaction with areas of damage blood vessel wall. Thus, it could be interesting to evaluate the possible influence of the ABO group in this interaction, particularly in situations in which low levels of VWF are close to those found in VW disease (such in O group). Cone and plate(let) analyzer (CPA) represent a simple and fast method, that allow the evaluation of platelet function (adhesion as well aggregation) in whole blood under shear conditions, closer to physiological conditions. In this method, no platelet agonists are needed and interaction with fibrinogen and VWF is particularly evaluated. The aim of the present study was to evaluate the influence of ABO group in platelet function using CPA. Samples from 15 male blood donors with no history of drug intake, were submitted to ABO serology and molecular analysis, VWF:Ag, FVIII dosages, and CPA analysis using Impact-R (Diamed - Switzerland), according to manufacturer’s instructions. ABO phenotypes were determined by agglutination test using monoclonal and polyclonal anti-A, B and AB antibodies (Asem-NPBI, São Paulo Brazil; DiaMed SA, Suisse; DiaMed Latino América, Brazil). H antigen was determined using anti-H lectin from Ulex europaeus (DiaMed Latino América, Brazil). ABO genotyping was performed by polymerase chain reaction (PCR) amplification of exons 6 and 7 of the ABO gene, followed by diagnostic restriction enzyme digestion. Factor VIII coagulant was measured by a one stage clothing method using a factor-VIII deficient substrate. VWF:Ag was measured by an enzyme linked immunosorbent assay (ELISA) using polyclonal antiserum (Dako, Denmark). Lyophilised commercial reference preparations of VWF:Ag, and FVIII, standardized against the World Health Organization standard, were used as the standards in this study. The age of the donors ranged from 27–65 years (median = 42 years). The donors were distributed according to ABO groups: 5 = OO; 5 = AB; 5 = AO. Median levels of factor VIII, according to blood group were: OO= 79% (70–142%); AO= 87% (80–140%); AB= 112% (98–200%). Median levels of VWF, according to blood group were: OO= 79% (50–99%); AO= 82% (73–120%); AB= 169% (92–250%). CPA analysis presented the following results: median AS in μm2 (average size) - OO= 24 (23–42); AO= 33 (24–42); AB= 23 (21–24) - median SC in % (surface coverage) - OO= 7.1 (4–13); AO= 8 (5–8); AB= 6.9 (4.8–8). No significant differences using Wilcoxon’s rank sum test were found among groups, when platelet function was analyzed. In conclusion, our results suggest that, although O allele carriers present lower levels of both factor VIII and VWF, the use of platelet function analysis does not seem to predict the risk for bleeding or thrombosis, according to individual ABO blood group.


2018 ◽  
Vol 29 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Abdullah Alharbi ◽  
Salwa Bakr Hassan ◽  
Abdul-Kareem Al-Momen ◽  
Khalid Al-Saleh ◽  
Rasheed Nasr ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document