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. 1979 Oct;76(10):5317–5320. doi: 10.1073/pnas.76.10.5317

Platelet receptors for human Factor VIII/von Willebrand protein: functional correlation of receptor occupancy and ristocetin-induced platelet aggregation.

K J Kao, S V Pizzo, P A McKee
PMCID: PMC413133  PMID: 315561

Abstract

Previous studies of von Willebrand disease indicate that a deficiency of blood clotting Factor VIII/von Willebrand factor (FVIII/vWF) activity is responsible for the failure of platelets to participate fully in the initial stages of hemostasis. We have recently identified specific FVIII/vWF binding sites on platelets, suggesting that the interaction of these sites with FVIII/vWF may be functionally important in the development of platelet clumps. We have now studied how different ristocetin concentrations, various known platelet aggregation inhibitors, and the exposure of platelets to proteases affect the ability of platelets to bind FVIII/vWF and to form aggregates. Our results demonstrate a highly significant linear correlation between the degree of FVIII/vWF receptor binding and the extent of ristocetin-induced platelet aggregation. Because neither FVIII/vWF binding nor platelet aggregation occurs after platelets are exposed to low concentrations of proteases, the FVIII/vWF receptors must be in the platelet membrane. We conclude that the interaction between FVIII/vWF protein and its receptors on the platelet membrane is an important mechanism by which platelet aggregation occurs during primary phase hemostasis.

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Selected References

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

  1. BIGGS R., MATTHEWS J. M. The treatment of haemorrhage in von Willebrand's disease and the blood level of factor VIII (AHG). Br J Haematol. 1963 Apr;9:203–214. doi: 10.1111/j.1365-2141.1963.tb05458.x. [DOI] [PubMed] [Google Scholar]
  2. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. CORNU P., LARRIEU M. J., CAEN J., BERNARD J. Transfusion studies in von Willebrand's disease: effect on bleeding time and factor VIII. Br J Haematol. 1963 Apr;9:189–202. doi: 10.1111/j.1365-2141.1963.tb05457.x. [DOI] [PubMed] [Google Scholar]
  5. Hovig T., Stormorken H. Ultrastructural studies on the platelet plug formation in bleeding time wounds from normal individuals and patients with von Willebrand's disease. Acta Pathol Microbiol Scand Suppl. 1974;Suppl 248:105–122. [PubMed] [Google Scholar]
  6. Howard M. A. Inhibition and reversal of ristocetin - induced platelet aggregation. Thromb Res. 1975 Jun;6(6):489–499. doi: 10.1016/0049-3848(75)90061-4. [DOI] [PubMed] [Google Scholar]
  7. Howard M. A., Sawers R. J., Firkin B. G. Ristocetin: a means of differentiating von Willebrand's disease into two groups. Blood. 1973 May;41(5):687–690. [PubMed] [Google Scholar]
  8. Jenkins C. S., Phillips D. R., Clemetson K. J., Meyer D., Larrieu M. J., Lüscher E. F. Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease. J Clin Invest. 1976 Jan;57(1):112–124. doi: 10.1172/JCI108251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kao K. J., Pizzo S. V., McKee P. A. Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets. J Clin Invest. 1979 Apr;63(4):656–664. doi: 10.1172/JCI109348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kirby E. P. Evans blue: a specific inhibitor of factor VIII-induced platelet agglutination. Thromb Diath Haemorrh. 1975 Dec 15;34(3):770–779. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. NILSSON I. M., BLOMBACK M., JORPES E., BLOMBACK B., JOHANSSON S. A. Von Willebrand's disease and its correction with human plasma fraction 1-0. Acta Med Scand. 1957 Nov 29;159(3):179–188. doi: 10.1111/j.0954-6820.1957.tb00123.x. [DOI] [PubMed] [Google Scholar]
  14. Nachman R. L., Jaffe E. A., Weksler B. B. Immunoinhibition of ristocetin-induced platelet aggregation. J Clin Invest. 1977 Jan;59(1):143–148. doi: 10.1172/JCI108612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Okumura T., Jamieson G. A. Platelet glycocalicin: a single receptor for platelet aggregation induced by thrombin or ristocetin. Thromb Res. 1976 May;8(5):701–706. doi: 10.1016/0049-3848(76)90250-4. [DOI] [PubMed] [Google Scholar]
  16. Paulssen M. M., van de Graaf-Wildschut M., Kolhorn A., Planje M. C. Radioimmunoassay of antihaemophilic factor (factor VIII) antigen. Clin Chim Acta. 1975 Sep 16;63(3):349–353. doi: 10.1016/0009-8981(75)90056-x. [DOI] [PubMed] [Google Scholar]
  17. Platelet aggregation: Part II Some results from a new method of study. J Clin Pathol. 1962 Sep;15(5):452–455. doi: 10.1136/jcp.15.5.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Switzer M. E., McKee P. A. Studies on human antihemophilic factor. Evidence for a covalently linked subunit structure. J Clin Invest. 1976 Apr;57(4):925–937. doi: 10.1172/JCI108369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Weiss H. J., Rogers J., Brand H. Defective ristocetin-induced platelet aggregation in von Willebrand's disease and its correction by factor VIII. J Clin Invest. 1973 Nov;52(11):2697–2707. doi: 10.1172/JCI107464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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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