Abstract
Aggregation of human platelets by bovine plasma was recently recognized as a marker for the study of the antihemophilic and von Willebrand factors. A similar marker in porcine plasma is shown to be specific for the platelet-active von Willebrand factor of plasma, but not for the antihemophilic factor (factor VIII). A new quantitative assay for the von Willebrand factor is based on the dose-response relationship observed between the concentration of von Willebrand factor and platelet aggregation times determined macroscopically. Bleeder swine, homozygous for von Willebrand disease, had no detectable platelet aggregating activity, while heterozygotes, carriers of the disease, had reduced levels of approximately 50% of normal. Exact detection of non-obligate carriers, hitherto impossible, becomes readily feasible because of the gene dosage relationship to the von Willebrand factor plasma levels. Transfusion of bleeder swine with normal plasma results in an immediate post-transfusion rise of the von Willebrand factor, followed by a rapid falloff. At 24 hr post-transfusion, no von Willebrand factor is detectable at a time when the factor VIII response is at its maximum. The discordance in plasma levels of this platelet-active von Willebrand factor and factor VIII in carrier animals and in the bleeder animals after transfusion suggests a different molecular and genetic basis for these two biological activities.
Keywords: von Willebrand disease, genetic marker, platelet aggregation, macromolecules and hemostasis, factor VIII
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BRINKHOUS K. M., LEROY E. C., CORNELL W. P., BROWN R. C., HAZLEHURST J. L., VENNART G. P. Macroscopic studies of platelet agglutination; nature of thrombocyte agglutinating activity of plasma. Proc Soc Exp Biol Med. 1958 Jun;98(2):379–383. doi: 10.3181/00379727-98-24050. [DOI] [PubMed] [Google Scholar]
- Bowie E. J., Owen C. A., Jr, Zollman P. E., Thompson J. H., Jr, Fass D. N. Tests of hemostasis in swine: normal values and values in pigs affected with von Willebrand's disease. Am J Vet Res. 1973 Nov;34(11):1405–1407. [PubMed] [Google Scholar]
- CORNELL C. N., MUHRER M. E. COAGULATION FACTORS IN NORMAL AND HEMOPHILIAC-TYPE SWINE. Am J Physiol. 1964 Apr;206:926–928. doi: 10.1152/ajplegacy.1964.206.4.926. [DOI] [PubMed] [Google Scholar]
- Chan J. Y., Owen C. A., Jr, Bowie E. J., Didisheim P., Thompson J. H., Jr, Muhrer M. E., Zollman P. E. Von Willebrand disease "stimulating factor" in porcine plasma. Am J Physiol. 1968 May;214(5):1219–1224. doi: 10.1152/ajplegacy.1968.214.5.1219. [DOI] [PubMed] [Google Scholar]
- Cornell C. N., Cooper R. G., Kahn R. A., Garb S. Platelet adhesiveness in normal and bleeder swine as measured in a Celite system. Am J Physiol. 1969 May;216(5):1170–1175. doi: 10.1152/ajplegacy.1969.216.5.1170. [DOI] [PubMed] [Google Scholar]
- Forbes C. D., Prentice C. R. Aggregation of human platelets by purified porcine and bovine antihaemophilic factor. Nat New Biol. 1973 Jan 31;241(109):149–150. doi: 10.1038/newbio241149a0. [DOI] [PubMed] [Google Scholar]
- Griggs T. R., Cooper H. A., Webster W. P., Wagner R. H., Brinkhous K. M. Plasma aggregating factor (bovine) for human platelets: a marker for study of antihemophilic and von Willebrand Factors. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2814–2818. doi: 10.1073/pnas.70.10.2814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LANGDELL R. D., WAGNER R. H., BRINKHOUS K. M. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med. 1953 Apr;41(4):637–647. [PubMed] [Google Scholar]
- MUHRER M. E., LECHLER E., CORNELL C. N., KIRKLAND J. L. ANTIHEMOPHILIC FACTOR LEVELS IN BLEEDER SWINE FOLLOWING INFUSIONS OF PLASMA AND SERUM. Am J Physiol. 1965 Mar;208:508–510. doi: 10.1152/ajplegacy.1965.208.3.508. [DOI] [PubMed] [Google Scholar]
- Tangen O., Berman H. J., Marfey P. Gel filtration. A new technique for separation of blood platelets from plasma. Thromb Diath Haemorrh. 1971 Jun 30;25(2):268–278. [PubMed] [Google Scholar]