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

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.

[1]  M. Laffan,et al.  Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis. , 2005, Blood.

[2]  W. Chng,et al.  Differential effect of the ABO blood group on von Willebrand factor collagen binding activity and ristocetin cofactor assay , 2005, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[3]  A. Dick,et al.  Relationship between ABO and Secretor genotype with plasma levels of factor VIII and von Willebrand factor in thrombosis patients and control individuals , 2005, British journal of haematology.

[4]  D. Bowen Increased susceptibility of von Willebrand factor to proteolysis by ADAMTS13: should the multimer profile be normal or type 2A? , 2004, Blood.

[5]  Raymond A Dwek,et al.  Statistical analysis of the protein environment of N-glycosylation sites: implications for occupancy, structure, and folding. , 2003, Glycobiology.

[6]  P. Greenwell Blood group antigens: molecules seeking a function? , 1997, Glycoconjugate Journal.

[7]  B. Evatt,et al.  Measurement of von Willebrand factor activity: relative effects of ABO blood type and race , 2003, Journal of thrombosis and haemostasis : JTH.

[8]  P. Collins,et al.  Increased clearance of von Willebrand factor antigen post‐DDAVP in Type 1 von Willebrand disease: is it a potential pathogenic process? , 2003, Journal of thrombosis and haemostasis : JTH.

[9]  M. Laffan,et al.  Dissociation of ABH antigen expression from von Willebrand factor synthesis in endothelial cell lines , 2003, British journal of haematology.

[10]  D. Bowen,et al.  An influence of ABO blood group on the rate of proteolysis of von Willebrand factor by ADAMTS13 , 2003, Journal of thrombosis and haemostasis : JTH.

[11]  J. Sadler,et al.  ADAMTS13 and TTP , 2002, Current opinion in hematology.

[12]  A. Varki,et al.  Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Laffan,et al.  The Relationship Between Plasma Concentration of α2- Macroglobulin and AB0 Blood Group , 2002, Thrombosis and Haemostasis.

[14]  P. Collins,et al.  Heterogeneous Detection of A-antigen on von Willebrand Factor Derived from Platelets, Endothelial Cells and Plasma , 2002, Thrombosis and Haemostasis.

[15]  M. Laffan,et al.  Genotype at the Secretor blood group locus is a determinant of plasma von Willebrand factor level , 2002, British journal of haematology.

[16]  M. Laffan,et al.  Amount of H Antigen Expressed on Circulating von Willebrand Factor Is Modified by ABO Blood Group Genotype and Is a Major Determinant of Plasma von Willebrand Factor Antigen Levels , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[17]  M. Laffan,et al.  The relationship between plasma concentration of alpha2-macroglobulin and ABO blood group. , 2002, Thrombosis and haemostasis.

[18]  K. Fujikawa,et al.  Structure of von Willebrand Factor-cleaving Protease (ADAMTS13), a Metalloprotease Involved in Thrombotic Thrombocytopenic Purpura* , 2001, The Journal of Biological Chemistry.

[19]  T. Foroud,et al.  Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura , 2001, Nature.

[20]  M. Laffan,et al.  The relationship between ABO histo‐blood group, factor VIII and von Willebrand factor , 2001, Transfusion medicine.

[21]  M. Laffan,et al.  Human Umbilical Vein Endothelial Cells Differ from Other Endothelial Cells in Failing to Express ABO Blood Group Antigens , 2000, Journal of Vascular Research.

[22]  G. Garratty Blood groups and disease: a historical perspective. , 2000, Transfusion medicine reviews.

[23]  L. Almasy,et al.  Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[24]  R. Nagel,et al.  Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor , 2000, British journal of haematology.

[25]  J. Sixma,et al.  The Half-life of Infused Factor VIII Is Shorter in Hemophiliac Patients with Blood Group 0 than in those with Blood Group A , 2000, Thrombosis and Haemostasis.

[26]  F. Yamamoto,et al.  Molecular genetics of ABO. , 2000, Vox sanguinis.

[27]  K. Titani,et al.  ABO blood group antigens on human plasma von Willebrand factor after ABO-mismatched bone marrow transplantation. , 1999, Blood.

[28]  B. Lämmle,et al.  Von Willebrand Factor in Thrombotic Thrombocytopenic Purpura , 1999, Thrombosis and Haemostasis.

[29]  G. Lowe,et al.  Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study , 1999, British journal of haematology.

[30]  K. Mohlke,et al.  Mvwf, a Dominant Modifier of Murine von Willebrand Factor, Results from Altered Lineage-Specific Expression of a Glycosyltransferase , 1999, Cell.

[31]  T. Eastlund The histo‐blood group ABO system and tissue transplantation , 1998, Transfusion.

[32]  M. Bonneau,et al.  Effects of human recombinant, plasma-derived and porcine von Willebrand factor in pigs with severe von Willebrand disease. , 1998, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[33]  R. Kaufman,et al.  Post-translational Modifications Required for Coagulation Factor Secretion and Function , 1998, Thrombosis and Haemostasis.

[34]  S. Perkins,et al.  Molecular modeling of ligand and mutation sites of the type A domains of human von Willebrand factor and their relevance to von Willebrand's disease. , 1998, Blood.

[35]  J. Sixma,et al.  Factor VIII and von Willebrand Factor , 1998, Thrombosis and Haemostasis.

[36]  F. Cohen,et al.  Biochemistry and genetics of von Willebrand factor. , 1998, Annual review of biochemistry.

[37]  P. V. van Genderen,et al.  Decreased half‐life time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: normalization after cytoreduction of the increased platelet count , 1997, British journal of haematology.

[38]  J. V. van Mourik,et al.  In vivo characterization of recombinant von Willebrand factor in dogs with von Willebrand disease. , 1997, Blood.

[39]  D. Ginsburg,et al.  Von Willebrand disease. , 2008, Pediatric clinics of North America.

[40]  J. Stoddart,et al.  Clearance of normal and type 2A von Willebrand factor in the rat. , 1996, Blood.

[41]  J. Sixma,et al.  A3 Domain Is Essential for Interaction of von Willebrand Factor with Collagen Type III , 1996, Thrombosis and Haemostasis.

[42]  K. Titani,et al.  ABO Blood Group Genotype and Plasma von Willebrand Factor in Normal Individuals , 1995, Vox sanguinis.

[43]  C. Samama,et al.  Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Vandenbroucke,et al.  Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis , 1995, The Lancet.

[45]  J. Williams,et al.  Solid-phase von Willebrand factor contains a conformationally active RGD motif that mediates endothelial cell adhesion through the alpha v beta 3 receptor. , 1993, Blood.

[46]  K. Titani,et al.  Human plasma alpha 2-macroglobulin and von Willebrand factor possess covalently linked ABO(H) blood group antigens in subjects with corresponding ABO phenotype. , 1993, Blood.

[47]  J. Lowe 7 The blood group-specific human glycosyltransferases , 1993 .

[48]  D. Baruch,et al.  Localization of von Willebrand factor binding domains to endothelial extracellular matrix and to type VI collagen. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[49]  J. Lowe The blood group-specific human glycosyltransferases. , 1993, Bailliere's clinical haematology.

[50]  J. Sweeney,et al.  Intraplatelet von Willebrand factor and ABO blood group. , 1992, Thrombosis research.

[51]  D. Lynch,et al.  O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b. , 1992, The Journal of clinical investigation.

[52]  K. Titani,et al.  Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. , 1992, The Journal of biological chemistry.

[53]  R. Oriol,et al.  Genetic regulation of the expression of ABH and Lewis antigens in tissues. , 1992, APMIS. Supplementum.

[54]  G. Strecker,et al.  Primary structure of the major O-glycosidically linked carbohydrate unit of human von Willebrand factor. , 1989, Glycoconjugate journal.

[55]  H. Reisner,et al.  Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor. , 1989, Blood.

[56]  R. Houghten,et al.  Structure of the von Willebrand factor domain interacting with glycoprotein Ib. , 1988, The Journal of biological chemistry.

[57]  S. Berkowitz,et al.  Sialic acid prevents loss of large von Willebrand factor multimers by protecting against amino-terminal proteolytic cleavage. , 1988, Blood.

[58]  K. Titani,et al.  A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. , 1987, The Journal of biological chemistry.

[59]  W. Marks,et al.  The effect of ABO blood group on the diagnosis of von Willebrand disease. , 1987, Blood.

[60]  J. Sixma,et al.  Structure-function relationship of human von Willebrand factor. , 1987, Blood.

[61]  R. D. Wade,et al.  Amino acid sequence of human von Willebrand factor. , 1986, Biochemistry.

[62]  P. Magnus,et al.  Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level. , 1985, American journal of human genetics.

[63]  A. Federici,et al.  Carbohydrate moiety of von Willebrand factor is not necessary for maintaining multimeric structure and ristocetin cofactor activity but protects from proteolytic degradation. , 1984, The Journal of clinical investigation.

[64]  D. Wagner,et al.  Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization , 1984, The Journal of cell biology.

[65]  A. P. Chauhan,et al.  Major Blood Group Antigens - A Determinant of Factor VIII Levels in Blood? , 1984, Thrombosis and Haemostasis.

[66]  R. Newcombe,et al.  Factor VIII Levels and Blood Group Antigens , 1983, Thrombosis and Haemostasis.

[67]  T. Feizi Blood group antigens and gastric cancer. , 1982, Medical biology.

[68]  L. Bell,et al.  Ultrastructural localisation of alkaline phosphatase in adult human large intestine. , 1982, Gut.

[69]  G. Ashwell,et al.  Carbohydrate-specific receptors of the liver. , 1982, Annual review of biochemistry.

[70]  Z. Ruggeri,et al.  The complex multimeric composition of factor VIII/von Willebrand factor. , 1981, Blood.

[71]  S. Pizzo,et al.  Factor VIII/von Willebrand protein. Modification of its carbohydrate causes reduced binding to platelets. , 1980, The Journal of biological chemistry.

[72]  P. McKee,et al.  Carbohydrate composition and identification of blood group A, B, and H oligosaccharide structures on human Factor VIII/von Willebrand factor. , 1979, Journal of Biological Chemistry.

[73]  S. Pizzo,et al.  Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. , 1977, The Journal of biological chemistry.

[74]  J. Medalie,et al.  Blood groups, myocardial infarction and angina pectoris among 10,000 adult males. , 1971, The New England journal of medicine.

[75]  M. Langman Relationship between pre-operative bleeding and perforation and bleeding after operations for duodenal ulcer , 1965, Gut.

[76]  H. Bentall,et al.  Relationship Between Cancer of Stomach and the ABO Blood Groups , 1953, British medical journal.