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. 1975 Oct;56(4):814–827. doi: 10.1172/JCI108160

Studies of the human factor VIII/von Willebrand factor protein. III. Qualitative defects in von Willebrand's disease.

H R Gralnick, B S Coller, Y Sultan
PMCID: PMC301936  PMID: 1080491

Abstract

The Factor VIII/von Willebrand factor protein was characterized in two unrelated patients with von Willebrand's disease in whom procoagulant and Factor VIII/von Willebrand factor antigen levels were normal. In both patients evidence of an abnormal protein was observed on crossed antigen-antibody electrophoresis. In one patient the Factor VIII/von Willebrand factor protein eluted from Sepharose 4B in a position and distribution identical to normal with normal levels of procoagulant activity and antigen. However, the partially purified Factor VIII/von Willebrand factor protein had markedly reduced von Willebrand factor activity in a ristocetin assay. In the second patient the peak of Factor VIII/von Willebrand factor protein, antigen, and procoagulant activity eluted from a Sepharose 4B column with an estimated molecular weight of approximately half that of normal. This protein had no von Willebrand factor activity. In both patients the reduced Factor VIII/von Willebrand factor protein subunit was indistinguishable from normal on polyacrylamide gel electrophoresis. These studies indicate that in some patients with von Willebrand's disease there is a qualitative defect of the Factor VII/von Willebrand factor protein; the total amount of protein, antigen, and procoagulant activity are normal while the von Willebrand factor activity is deficient.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BORN G. V., CROSS M. J. THE AGGREGATION OF BLOOD PLATELETS. J Physiol. 1963 Aug;168:178–195. doi: 10.1113/jphysiol.1963.sp007185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett B., Forman W. B., Ratnoff O. D. Studies on the nature of antihemophilic factor (factor VIII). Further evidence relating the AHF-like antigens in normal and hemophilic plasmas. J Clin Invest. 1973 Sep;52(9):2191–2197. doi: 10.1172/JCI107404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennett B., Ratnoff O. D., Levin J. Immunologic studies in von Willebrand's disease. Evidence that the antihemophilic factor (AHF) produced after transfusions lacks an antigen associated with normal AHF and the inactive material produced by patients with classic hemophilia. J Clin Invest. 1972 Oct;51(10):2597–2601. doi: 10.1172/JCI107077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowie E. J., Owen C. A., Jr, Thompson J. H., Didisheim P. Platelet adhesiveness in von Willebrand's disease. Am J Clin Pathol. 1969 Jul;52(1):69–77. doi: 10.1093/ajcp/52.1.69. [DOI] [PubMed] [Google Scholar]
  5. Firkin B., Firkin F., Stott L. Von Willebrand's disease type B: a newly defined bleeding diathesis. Aust N Z J Med. 1973 Jun;3(3):225–229. doi: 10.1111/j.1445-5994.1973.tb03086.x. [DOI] [PubMed] [Google Scholar]
  6. Gralnick H. R., Coller B. S., Marchesi S. L. Studies of the human factor VIII/von Willebrand's factor protein I. Comparison of the protein found in normal, von Willebrand's disease and hemophilia A. Thromb Res. 1975 Feb;6(2):93–108. doi: 10.1016/0049-3848(75)90015-8. [DOI] [PubMed] [Google Scholar]
  7. Holmberg L., Nilsson I. M. Two genetic variants of von Willebrand's disease. N Engl J Med. 1973 Mar 22;288(12):595–598. doi: 10.1056/NEJM197303222881202. [DOI] [PubMed] [Google Scholar]
  8. Howard M. A., Firkin B. G. Ristocetin--a new tool in the investigation of platelet aggregation. Thromb Diath Haemorrh. 1971 Oct 31;26(2):362–369. [PubMed] [Google Scholar]
  9. Kass L., Ratnoff O. D., Leon M. A. Studies on the purification of antihemophilic factor (factor 8. I. Precipitation of antihemophilic factor by concanavalin A. J Clin Invest. 1969 Feb;48(2):351–358. doi: 10.1172/JCI105991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kernoff P. B., Gruson R., Rizza C. R. A variant of factor 8 related antigen. Br J Haematol. 1974 Mar;26(3):435–440. doi: 10.1111/j.1365-2141.1974.tb00484.x. [DOI] [PubMed] [Google Scholar]
  11. LAURELL C. B. ANTIGEN-ANTIBODY CROSSED ELECTROPHORESIS. Anal Biochem. 1965 Feb;10:358–361. doi: 10.1016/0003-2697(65)90278-2. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. doi: 10.1016/0003-2697(66)90246-6. [DOI] [PubMed] [Google Scholar]
  14. Legaz M. E., Schmer G., Counts R. B., Davie E. W. Isolation and characterization of human Factor VIII (antihemophilic factor). J Biol Chem. 1973 Jun 10;248(11):3946–3955. [PubMed] [Google Scholar]
  15. Marchesi S. L., Shulman N. R., Gralnick H. R. Studies on the purification and characterization of human factor 8. J Clin Invest. 1972 Aug;51(8):2151–2161. doi: 10.1172/JCI107022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Martinez J., Holburn R. R., Shapiro S. S., Erslev A. J. Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism. J Clin Invest. 1974 Feb;53(2):600–611. doi: 10.1172/JCI107595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ménaché D. Abnormal fibrinogens. A review. Thromb Diath Haemorrh. 1973 Jun 28;29(3):525–535. [PubMed] [Google Scholar]
  18. Peake I. R., Bloom A. L., Giddings J. C. Inherited variants of factor-VIII-related protein in von Willebrand's disease. N Engl J Med. 1974 Jul 18;291(3):113–117. doi: 10.1056/NEJM197407182910301. [DOI] [PubMed] [Google Scholar]
  19. SALZMAN E. W. MEASUREMENT OF PLATELET ADHESIVENESS. A SIMPLE IN VITRO TECHNIQUE DEMONSTRATING AN ABNORMALITY IN VON WILLEBRAND'S DISEASE. J Lab Clin Med. 1963 Nov;62:724–735. [PubMed] [Google Scholar]
  20. Serjeant G. R., Ashcroft M. T., Serjeant B. E. The clinical features of haemoglobin SC disease in Jamaica. Br J Haematol. 1973 Apr;24(4):491–501. doi: 10.1111/j.1365-2141.1973.tb01675.x. [DOI] [PubMed] [Google Scholar]
  21. Shapiro A. L., Viñuela E., Maizel J. V., Jr Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem Biophys Res Commun. 1967 Sep 7;28(5):815–820. doi: 10.1016/0006-291x(67)90391-9. [DOI] [PubMed] [Google Scholar]
  22. Shapiro G. A., Andersen J. C., Pizzo S. V., McKee P. A. The subunit structure of normal and hemophilic factor VIII. J Clin Invest. 1973 Sep;52(9):2198–2210. doi: 10.1172/JCI107405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simone J. V., Vanderheiden J., Abildgaard C. F. A semiautomatic one-stage factor 8 assay with a commercially prepared standard. J Lab Clin Med. 1967 Apr;69(4):706–712. [PubMed] [Google Scholar]
  24. Stites D. P., Hershgold E. J., Perlman J. D., Fudenberg H. H. Factor 8 detection by hemagglutination inhibition: hemophilia A and von Willebrand's disease. Science. 1971 Jan 15;171(3967):196–197. doi: 10.1126/science.171.3967.196. [DOI] [PubMed] [Google Scholar]
  25. Thomson C., Forbes C. D., Prentice C. R. Evidence for a qualitative defect in factor-VIII-related antigen in von Willebrand's disease. Lancet. 1974 Apr 6;1(7858):594–596. doi: 10.1016/s0140-6736(74)92652-x. [DOI] [PubMed] [Google Scholar]
  26. Weiss H. J., Hoyer L. W., Rickles F. R., Varma A., Rogers J. Quantitative assay of a plasma factor deficient in von Willebrand's disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content. J Clin Invest. 1973 Nov;52(11):2708–2716. doi: 10.1172/JCI107465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zimmerman T. S., Ratnoff O. D., Powell A. E. Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand's dissase, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest. 1971 Jan;50(1):244–254. doi: 10.1172/JCI106480. [DOI] [PMC free article] [PubMed] [Google Scholar]

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