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Thromb Haemost 2002; 87(02): 252-257
DOI: 10.1055/s-0037-1612981
Letters to the Editor
Schattauer GmbH

The Factor VIII/Von Willebrand Factor Ratio Discriminates between Reduced Synthesis and Increased Clearance of Von Willebrand Factor

Jeroen C. J. Eikenboom
1   Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden, The Netherlands
,
Giancarlo Castaman
3   Hemophilia and Thrombosis Center, Department of Hematology, San Bortolo Hospital, Vicenza, Italy
,
Pieter W. Kamphuisen
1   Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden, The Netherlands
,
Frits R. Rosendaal
1   Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden, The Netherlands
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Rogier M. Bertina
1   Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 18 June 2001

Accepted after revision 29 October 2001

Publication Date:
13 December 2017 (online)

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Summary

It is often stated that a decrease in Von Willebrand factor (VWF), the carrier protein of factor VIII, results in a concordant change in factor VIII. Clinical data suggest that this is not always the case and we hypothesized that the ratio between factor VIII and VWF depends on the genetic defect that causes the VWF deficiency. We have analyzed the ratio between plasma factor VIII and VWF in several subtypes of Von Willebrand Disease and we show that the ratio is increased when VWF synthesis is reduced, but that the ratio remains one when VWF clearance is increased. These observations could be of clinical importance as an increased factor VIII/VWF ratio in combination with a borderline VWF level may indicate the presence of a true genetic defect, possibly a VWF null allele.

Keywords

Factor VIII - Willebrand - mutations - blood group - null alleles
 

  • References

  • 1 Hoyer LW, Shainoff JR. Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers. Blood 1980; 55: 1056-9.
    PubMedGoogle Scholar
  • 2 Weiss HJ, Sussman I, Hoyer LW. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand’s disease. J Clin Invest 1977; 60: 390-404.
    CrossrefPubMedGoogle Scholar
  • 3 Veltkamp J, Tilburg NH. Detection of heterozygotes for recessive von Willebrand’s disease by the assay of antihemophilic-factor-like antigen. N Engl J Med 1973; 289: 882-5.
    CrossrefPubMedGoogle Scholar
  • 4 Kaufman RJ, Pipe SW. Regulation of factor VIII expression and activity by von Willebrand factor. Thromb Haemost 1999; 82: 201-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Vlot AJ, Koppelman SJ, Van den Berg MH, Bouma BN, Sixma J. The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor. Blood 1995; 85: 3150-7.
    PubMedGoogle Scholar
  • 6 Ngo KY, Glotz VT, Koziol JA, Lynch DC, Gitschier J, Ranieri P, Ciavarella N, Ruggeri ZM, Zimmerman TS. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease. Proc Natl Acad Sci USA 1988; 85: 2753-7.
    CrossrefPubMedGoogle Scholar
  • 7 Peake IR, Liddell MB, Moodie P, Standen G, Mancuso DJ, Tuley EA, Westfield LA, Sorace JM, Sadler JE, Verweij CL. Severe type III von Willebrand’s disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual. Blood 1990; 75: 654-61.
    PubMedGoogle Scholar
  • 8 Nichols WC, Lyons SE, Harrison JS, Cody RL, Ginsburg D. Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: detection by exonic PCR-restriction fragment length polymorphism analysis. Proc Natl Acad Sci USA 1991; 88: 3857-61.
    CrossrefPubMedGoogle Scholar
  • 9 Bahnak BR, Lavergne JM, Rothschild C, Meyer D. A stop codon in a patient with severe type III von Willebrand disease [letter]. Blood 1991; 78: 1148-9.
    PubMedGoogle Scholar
  • 10 Zhang ZP, Lindstedt M, Falk G, Blombäck M, Egberg N, Anvret M. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. Am J Hum Genet 1992; 51: 850-8.
    PubMedGoogle Scholar
  • 11 Eikenboom JCJ, Reitsma PH, Peerlinck KMJ, Briët E. Recessive inheritance of von Willebrand’s disease type I. Lancet 1993; 341: 982-6.
    CrossrefPubMedGoogle Scholar
  • 12 Schneppenheim R, Krey S, Bergmann F, Bock D, Budde U, Lange M, Linde R, Mittler U, Meili E, Mertes G, Olek K, Plendl H, Simeoni E. Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet 1994; 94: 640-52.
    PubMedGoogle Scholar
  • 13 Zhang ZP, Lindstedt M, Blombäck M, Anvret M. Effects of the mutant von Willebrand factor gene in von Willebrand disease. Hum Genet 1995; 96: 388-94.
    PubMedGoogle Scholar
  • 14 Eikenboom JCJ, Castaman G, Vos HL, Bertina RM, Rodeghiero F. Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin. Thromb Haemost 1998; 79: 709-17.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Casonato A, Gaucher C, Pontara E, Zucchetto A, Zerbinati P, Mazurier C, Girolami A. Type 2N von Willebrand disease due to Arg91Gln substitution and a cytosine deletion in exon 18 of the von Willebrand factor gene. Br J Haematol 1998; 103: 39-41.
    CrossrefPubMedGoogle Scholar
  • 16 Siguret V, Lavergne J-M, Cherel G, Boyer-Neumann C, Ribba A-S, Bahnak BR, Meyer D, Pietu G. A novel case of compound heterozygosity with “Normandy”/type I von Willebrand disease (vWD). Direct demonstration of the segregation of one allele with a defective expression at the mRNA level causing type I vWD. Hum Genet 1994; 93: 95-102.
    PubMedGoogle Scholar
  • 17 Jorieux S, Gaucher C, Goudemand J, Mazurier C. A novel mutation in the D3 domain of von Willebrand factor markedly decreases its ability to bind factor VIII and affects its multimerization. Blood 1998; 92: 4663-70.
    CrossrefPubMedGoogle Scholar
  • 18 Casana P, Martinez F, Haya S, Lorenzo JI, Espinos C, Aznar JA. Q1311X: a novel nonsense mutation of putative ancient origin in the von willebrand factor gene. Br J Haematol 2000; 111: 552-5.
    CrossrefPubMedGoogle Scholar
  • 19 Sugiura I, Matsushita T, Tanimoto M, Takahashi I, Yamazaki T, Yamamoto K, Takamatsu J, Kamiya T, Saito H. Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. Thromb Haemost 1992; 67: 612-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Lavergne J-M, De Paillette L, Bahnak BR, Ribba A-S, Fressinaud E, Meyer D, Pietu G. Defects in type IIA von Willebrand disease: A cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX. Br J Haematol 1992; 82: 66-72.
    CrossrefPubMedGoogle Scholar
  • 21 Pietu G, Ribba A-S, De Paillette L, Cherel G, Lavergne LM, Bahnak BR, Meyer D. Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB. Bl Coag Fibrinol 1992; 03: 415-21.
    PubMedGoogle Scholar
  • 22 Donner M, Kristoffersson A-C, Berntorp E, Scheibel E, Thorsen S, Dahlbäck B, Nilsson IM, Holmberg L. Two new candidate mutations in type IIA von Willebrand’s disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor. Eur J Haematol 1993; 51: 38-44.
    PubMedGoogle Scholar
  • 23 Iannuzzi MC, Hidaka N, Boehnke M, Bruck ME, Hanna WT, Collins FS, Ginsburg D. Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (IIe865 to Thr). Am J Hum Genet 1991; 48: 757-63.
    PubMedGoogle Scholar
  • 24 Hanna W, McCarroll D, Lin D, Chua W, McDonald TP, Chen J, Congdon C, Lange RD. A study of a Caucasian family with variant von Willebrand’s disease in association with vascular telangiectasia and haemoglobinopathy. Thromb Haemost 1984; 51: 275-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Lyons SE, Cooney KA, Bockenstedt P, Ginsburg D. Characterization of Leu777Pro and Ile865Thr type IIA von Willebrand disease mutations. Blood 1994; 83: 1551-7.
    PubMedGoogle Scholar
  • 26 Green D, Philip KJ. Variant von Willebrand’s disease. A study emphasizing crossed-immunoelectrophoresis. Thromb Haemost 1980; 43: 2-5.
    PubMedGoogle Scholar
  • 27 Enayat MS, Guilliatt AM, Surdhar GK, Theophilus BD, Hill FG. A new candidate missense mutation (Leu 1657 IIe) in an apparently asymptomatic type 2A (phenotype IIA) von Willebrand disease family. Thromb Haemost 2000; 84: 369-73.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Lyons SE, Bruck ME, Bowie EJW, Ginsburg D. Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. J Biol Chem 1992; 267: 4424-30.
    PubMedGoogle Scholar
  • 29 Lankhof H, Damas C, Schiphorst ME, Ysseldijk MJW, Bracke M, Furlan M, De Groot PG, Sixma JJ, Vink T. Recombinant vWF type 2A mutants R834Q and R834W show a defect in mediating platelet adhesion to collagen, independent of enhanced sensitivity to a plasma protease. Thromb Haemost 1999; 81: 976-83.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Englender T, Lattuada A, Mannucci PM, Sadler JE, Inbal A. Analysis of Arg834Gln and Va1902Glu type 2A von Willebrand disease mutations. Studies with recombinant von Willebrand factor and correlation with patient characteristics. Blood 1996; 87: 2788-94.
    PubMedGoogle Scholar
  • 31 Ribba A-S, Voorberg J, Meyer D, Pannekoek H, Pietu G. Characterization of recombinant von Willebrand factor corresponding to mutations in type IIA and type IIB von Willebrand disease. J Biol Chem 1992; 267: 23209-15.
    PubMedGoogle Scholar
  • 32 Ribba AS, Lavergne JM, Bahnak BR, Derlon A, Pietu G, Meyer D. Duplication of a methionine within the glycoprotein Ib binding domain of von Willebrand factor detected by denaturing gradient gel electrophoresis in a patient with type IIB von Willebrand disease. Blood 1991; 78: 1738-43.
    PubMedGoogle Scholar
  • 33 Lillicrap D, Murray EW, Benford K, Blanchette VS, Rivard GE, Wensley R, Giles AR. Recurring mutations at CpG dinucleotides in the region of the von Willebrand factor gene encoding the glycoprotein Ib binding domain, in patients with type IIB von Willebrand’s disease. Br J Haematol 1991; 79: 612-7.
    CrossrefPubMedGoogle Scholar
  • 34 Donner M, Andersson AM, Kristoffersson AC, Nilsson IM, Dahlbaeck B, Holmberg L. An Arg545?Cys545 substitution mutation of the von Willebrand factor in type IIB von Willebrand’s disease. Eur J Haematol 1991; 47: 342-5.
    PubMedGoogle Scholar
  • 35 Randi AM, Rabinowitz I, Mancuso DJ, Mannucci PM, Sadler JE. Molecular basis of von Willebrand disease type IIB. Candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences. J Clin Invest 1991; 87: 1220-6.
    CrossrefPubMedGoogle Scholar
  • 36 Italian WG. Spectrum of von Willebrand’s Disease: a study of 100 cases. Br J Haematol 1977; 35: 101-12.
    CrossrefPubMedGoogle Scholar
  • 37 Donner M, Kristoffersson AC, Lenk H, Scheibel E, Dahlbäck B, Nilsson IM, Holmberg L. Type IIB von Willebrand’s disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden. Br J Haematol 1992; 82: 58-65.
    CrossrefPubMedGoogle Scholar
  • 38 Murray EW, Giles AR, Lillicrap D. Germ-line mosaicism for a valineto-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease. Am J Hum Genet 1992; 50: 199-207.
    PubMedGoogle Scholar
  • 39 Rabinowitz I, Randi AM, Shindler KS, Tuley EA, Rustagi PK, Sadler JE. Type IIB mutation His-505 --> Asp implicates a new segment in the control of von Willebrand factor binding to platelet glycoprotein Ib. J Biol Chem 1993; 268: 20497-501.
    PubMedGoogle Scholar
  • 40 Eikenboom JCJ, Reitsma PH, Briët E. Seeming homozygosity in type-IIB von Willebrand’s disease due to a polymorphism within the sequence of a commonly used primer. Ann Hematol 1994; 68: 139-41.
    CrossrefPubMedGoogle Scholar
  • 41 Hilbert L, Gaucher C, De Romeuf C, Horellou M-H, Vink T, Mazurier C. Leu 697 --> Val mutation in mature von Willebrand factor is responsible for type IIB von Willebrand disease. Blood 1994; 83: 1542-50.
    PubMedGoogle Scholar
  • 42 Gaucher C, De Romeuf C, Rauis-Morret M, Corazza F, Fondu P, Mazurier C. Diagnosis of subtype 2B von Willebrand disease in a patient with 2A phenotype of plasma von Willebrand factor. Thromb Haemost 1995; 73: 610-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Ribba AS, Christophe O, Derlon A, Cherel G, Siguret V, Lavergne JM, Girma JP, Meyer D, Pietu G. Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of von Willebrand disease. Blood 1994; 83: 833-41.
    PubMedGoogle Scholar
  • 44 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrle PA, Yoshioka A, Ruggeri ZM. Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor. Proc Natl Acad Sci USA 1991; 88: 2946-50.
    CrossrefPubMedGoogle Scholar
  • 45 Kyrle PA, Niessner H, Dent J, Panzer S, Brenner B, Zimmerman TS, Lechner K. IIB von Willebrand’s disease: pathogenetic and therapeutic studies. Br J Haematol 1988; 69: 55-9.
    CrossrefPubMedGoogle Scholar
  • 46 Wood N, Standen GR, Bowen DJ, Cumming A, Lush C, Lee R, Bidwell J. UHG-based mutation screening in type 2B von Willebrand’s disease: Detection of a candidate mutation Ser547Phe. Thromb Haemost 1996; 75: 363-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Federici AB, Mannucci PM, Stabile F, Canciani MT, Di Rocco N, Miyata S, Ware J, Ruggeri ZM. A type 2b van Willebrand disease mutation (Ile546-->Val) associated with an unusual phenotype. Thromb Haemost 1997; 78: 1132-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 De Romeuf C, Hilbert L, Mazurier C. Platelet activation and aggregation induced by recombinant von Willebrand factors reproducing four type 2B von Willebrand disease missense mutations. Thromb Haemost 1998; 79: 211-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Hilbert L, Gaucher C, Abgrall JF, Parquet A, Trzeciak C, Mazurier C. Identification of new type 2B von Willebrand disease mutations: Arg543Gln, Arg545Pro and Arg578Leu. Br J Haematol 1998; 103: 877-84.
    CrossrefPubMedGoogle Scholar
  • 50 Hilbert L, Gaucher C, Mazurier C. Effects of different amino-acid substitutions in the leucine 694-proline 708 segment of recombinant von Willebrand factor. Br J Haematol 1995; 91: 983-90.
    CrossrefPubMedGoogle Scholar
  • 51 Cooney KA, Ginsburg D. Comparative analysis of type 2b von Willebrand disease mutations: Implications for the mechanism of von Willebrand factor binding to platelets. Blood 1996; 87: 2322-8.
    PubMedGoogle Scholar
  • 52 Inbal A, Kornbrot N, Harrison P, Randi AM, Sadler JE. Effect of type IIB von Willebrand disease mutation Arg(545)Cys on platelet glycoprotein Ib binding--Studies with recombinant von Willebrand factor. Thromb Haemost 1993; 70: 1058-62.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Randi AM, Jorieux S, Tuley EA, Mazurier C, Sadler JE. Recombinant von Willebrand factor Arg578 --> Gln. A type IIB von Willebrand disease mutation affects binding to glycoprotein Ib but not to collagen or heparin. J Biol Chem 1992; 267: 21187-92.
    PubMedGoogle Scholar
  • 54 Kroner PA, Kluessendorf ML, Scott JP, Montgomery R. Expressed full-length von Willebrand factor containing missense mutations linked to type IIB von Willebrand disease shows enhanced binding to platelets. Blood 1992; 79: 2048-55.
    PubMedGoogle Scholar
  • 55 Lavergne JM, Piao Y, Ribba AS, Girma JP, Siguret V, Pi Gtu, Boyer-Neumann C, Schandelong A, Bahnak BR, Meyer D. Functional analysis of the Arg91Gln substitution in the factor VIII binding domain of von Willebrand factor demonstrates variable phenotypic expression. Thromb Haemost 1993; 70: 691-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 56 Wise RJ, Ewenstein BM, Gorlin J, Narins SC, Jesson M, Handin RI. Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation. Hum Genet 1993; 91: 367-72.
    PubMedGoogle Scholar
  • 57 Gaucher C, Jorieux S, Mercier B, Oufkir D, Mazurier C. The “Normandy” variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene. Blood 1991; 77: 1937-41.
    PubMedGoogle Scholar
  • 58 Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75: 20-6.
    PubMedGoogle Scholar
  • 59 Gaucher C, Mercier B, Jorieux S, Oufkir D, Mazurier C. Identification of two point mutations in the von Willebrand factor gene of three families with the ’Normandy’ variant of von Willebrand disease. Br J Haematol 1991; 78: 506-14.
    CrossrefPubMedGoogle Scholar
  • 60 Mazurier C, Gaucher C, Jorieux S, Parquet-Gernez A, Goudemand M. Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling. Br J Haematol 1990; 76: 372-9.
    CrossrefPubMedGoogle Scholar
  • 61 Gu J, Jorieux S, Lavergne JM, Ruan C, Mazurier C, Meyer D. Patient with type 2N von Willebrand disease is heterozygous for a new mutation: Gly22Glu. Demonstration of a defective expression of the second allele by the use of monoclonal antibodies. Blood 1997; 89: 3263-9.
    PubMedGoogle Scholar
  • 62 Schneppenheim R, Budde U, Krey S, Drewke E, Bergmann F, Lechler E, Oldenburg J, Schwaab R. Results of a screening for von Willebrand disease type 2N patients with suspected haemophilia A or van Willebrand disease type 1. Thromb Haemost 1996; 76: 598-602.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Kroner PA, Foster PA, Fahs SA, Montgomery R. The defective interaction between von Willebrand factor and factor VIII in a patient with type 1 von Willebrand disease is caused by substitution of Arg19 and His54 in mature von Willebrand factor. Blood 1996; 87: 1013-21.
    PubMedGoogle Scholar
  • 64 Nesbitt IM, Goodeve AC, Guilliatt AM, Makris M, Preston FE, Peake IR. Characterisation of type 2N von Willebrand disease using phenotypic and molecular techniques. Thromb Haemost 1996; 75: 959-64.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Peerlinck K, Eikenboom JCJ, Ploos HKvan Amstel, Sangtawesin W, Arnout J, Reitsma PH, Vermylen J, Briët E. A patient with von Willebrand’s disease characterized by a compound heterozygosity for a substitution of Arg854 by Gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele. Br J Haematol 1992; 80: 358-63.
    CrossrefPubMedGoogle Scholar
  • 66 Jorieux S, Tuley EA, Gaucher C, Mazurier C, Sadler JE. The mutation Arg (53)-->Trp causes von Willebrand disease Normandy by abolishing binding to factor VIII. Studies with recombinant von Willebrand factor. Blood 1992; 79: 563-7.
    PubMedGoogle Scholar
  • 67 Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C. Expression of von Willebrand factor “Normandy”: an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991; 88: 6377-81.
    CrossrefPubMedGoogle Scholar
  • 68 Kroner PA, Friedman KD, Fahs SA, Scott JP, Montgomery R. Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991; 266: 19146-9.
    PubMedGoogle Scholar
  • 69 Cacheris PM, Nichols WC, Ginsburg D. Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. J Biol Chem 1991; 266: 13499-502.
    PubMedGoogle Scholar
  • 70 Koster T, Blann AD, Briët E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
    CrossrefPubMedGoogle Scholar
  • 71 Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71: 520-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 72 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr. WJ, Montgomery R. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-5.
    PubMedGoogle Scholar
  • 73 Wahlberg TB, Blombäck M, Magnusson D. Influence of sex, blood group, secretor character, smoking habits, acetylsalicylic acid, oral contraceptives, fasting and general health state on blood coagulation variables in randomly selected young adults. Haemostasis 1984; 14: 312-9.
    PubMedGoogle Scholar
  • 74 Vlot AJ, Mauser-Bunschoten EP, Zarkova AG, Haan E, Kruitwagen CLJJ, Sixma JJ, Van den Berg HM. The half-life of infused factor VIII is shorter in hemophiliac patients with blood group O than in those with blood group. Thromb Haemost 2000; 83: 65-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 O’Donnell J, Tuddenham EGD, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: Role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Kamphuisen PW, Eikenboom JCJ, Rosendaal FR, Koster T, Blann AD, Vos HL, Bertina RM. High factor VIII antigen levels increase the risk of venous thrombosis but are not associated with polymorphisms in the von Willebrand factor and factor VIII gene. Br J Haematoll 2001; 115: 156-8.
    PubMedGoogle Scholar