Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

Ørstavik, K.H.; Kornstad, L.; Reisner, H; Berg, K.

doi:10.1182/blood.v73.4.990.bloodjournal734990

Cited by 24 publications

(33 citation statements)

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“…51 Furthermore, it has been recently described that the ABO blood group and secretor status have an effect on vWF and factor VIII plasma lev els, thus modifying the blood clotting ability. 62,63 The fact that we found a higher incidence of TRM only in the sub group of minor A and minor AB ABO mismatch is in accordance with other studies, and it is suggested that patients expressing the ABO blood group A antigen are at increased risk of complications after allo PBSCT. 2 A precise explanation for this has not yet been described.…”

Section: Discussionsupporting

confidence: 92%

ABO blood group antigen mismatch has an impact on outcome after allogeneic peripheral blood stem cell transplantation

Grube

Wolff

Ahrens

et al. 2016

Clinical Transplantation

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ABO blood group antigen incompatibility (ABO mismatch) is not an obstacle to allogeneic stem cell transplantation (allo-SCT). However, the impact on clinical outcome after allo-SCT remains controversial. We analyzed 512 patients after allogeneic peripheral blood SCT (allo-PBSCT) for an association of ABO mismatch with transfusion requirements, myeloid and platelet engraftment, the incidence of GvHD, relapse, transplant-related mortality (TRM), and overall survival (OS). A total of 260 patients underwent ABO-mismatched transplantation and the control group consisted of 252 patients with ABO-matched allo-PBSCT. We found a significant association between major-0 ABO mismatch (group 0 recipient/group A, B, or AB donor) and increased red blood cell (RBC) and platelet transfusion requirements (both P<.001) as well as delayed platelet engraftment (P<.001). Minor-A (group A recipient/group 0 donor) and minor-AB (group AB recipient/group 0, A, or B donor) ABO mismatch was significantly associated with an increased TRM after allo-PBSCT (P=.001 and P=.02). In multivariate analysis performed using Cox regression, minor ABO mismatch appeared as independent risk factor for TRM after allo-PBSCT. No association was found for ABO mismatch with the incidence of GvHD, relapse, and OS. Our results suggest that ABO blood group mismatch has a significant impact on the outcome and that minor-A and minor-AB ABO mismatch represents a risk factor for increased TRM after allo-PBSCT.

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Section: Discussionsupporting

confidence: 92%

ABO blood group antigen mismatch has an impact on outcome after allogeneic peripheral blood stem cell transplantation

Grube

Wolff

Ahrens

et al. 2016

Clinical Transplantation

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“…The ABO, Lewis, and Secretor blood group systems are characterized by the presence or absence of specific terminal carbohydrate determinants on oligosaccharide structures of glycoproteins or glycolipids. Orstavik and coworkers 51 were the first to describe an effect of Secretor blood group on plasma VWF concentration. In a study of 323 twins and 58 blood donors, they found significantly higher VWF:Ag levels in group O individuals with the RBC phenotype Le(a+b-) than in group O individuals with phenotypes Le(a-b+) or Le(a-b-), respectively.…”

Section: Secretor and Lewis Blood Group Systems And Plasma Vwf Levelsmentioning

confidence: 99%

ABO blood group determines plasma von Willebrand factor levels: a biologic function after all?

Jenkins¹,

O’Donnell²

2006

Transfusion

374

334

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For many years, an association between ABO histo-blood group and risk of thrombosis has been recognized. Blood group non-O (A, B, and AB) individuals have consistently been found to demonstrate increased incidence of both arterial and venous thrombotic disease, compared to group O individuals. This increased risk is attributable to the fact that ABO blood group influences plasma levels of a coagulation glycoprotein named von Willebrand factor (VWF). VWF levels are 25 percent higher in non-O compared to group O individuals. The mechanism by which ABO group determines plasma VWF levels has not been determined. ABO(H) carbohydrate antigenic determinants, however, are expressed on the N-linked glycan chains of circulating plasma VWF. This review will focus on the carbohydrate structures of VWF and recent studies suggesting that subtle variations in these structures (particularly differences in ABO blood group antigen expression) may have clinically significant effects on VWF proteolysis and clearance.

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“…Many factors can influence VWF levels including age, stress and hormonal status. The extent of effect on VWF levels attributable to the c.2771G>A allele may be confounded by ABO and other blood groups including Lewis [18] and Secretor [19]. Further loci influencing VWF levels have been sought but await characterization [20].…”

Section: In Vitro Expression Analysis Of Pr924qmentioning

confidence: 99%

von Willebrand factor variant p.Arg924Gln marks an allele associated with reduced von Willebrand factor and factor VIII levels

Hickson

Hampshire

Winship

et al. 2010

Journal of Thrombosis and Haemostasis

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Summary Background von Willebrand factor (VWF) variant c.2771G>A; p.R924Q has been described as a benign polymorphism or a possible marker for a null allele and been associated with mild bleeding phenotypes. It was identified in several patients in recent type 1 von Willebrand disease (VWD) studies. Objectives To determine whether the p.R924Q allele contributes to reduced VWF levels and type 1 VWD. Methods 1115 healthy controls and 148 index cases from the MCMDM-1VWD study were genotyped for c.2771G>A; VWF and FVIII levels were analysed in ABO blood group stratified individuals and the p.R924Q variant was expressed in 293 EBNA cells. Results c.2771G>A was present in six index cases, five of whom had a second VWF variant which likely contributed to phenotype. A common core haplotype identified in families, which included the rare G allele of c.5843-8C>G was present in the majority of 35 c.2771G>A heterozygous controls. c.2771G>A contributed about 10% variance in VWF and FVIII levels in controls and 35% variance when co-inherited with blood group O. Recombinant p.R924Q VWF had no effect on in vitro expression and heterozygous family members had normal VWFFVIII binding and normal clearance of VWF and FVIII. Conclusions The allele bearing c.2771A leads to reductions in VWF and FVIII levels particularly in combination with blood group O. Its inheritance alone may be insufficient for VWD diagnosis, but it appears to be associated with further VWF level reduction in individuals with a second VWF mutation and it contributes to population variance in VWF and FVIII levels.

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Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

Cited by 24 publications

References 0 publications

ABO blood group antigen mismatch has an impact on outcome after allogeneic peripheral blood stem cell transplantation

ABO blood group antigen mismatch has an impact on outcome after allogeneic peripheral blood stem cell transplantation

ABO blood group determines plasma von Willebrand factor levels: a biologic function after all?

von Willebrand factor variant p.Arg924Gln marks an allele associated with reduced von Willebrand factor and factor VIII levels

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