Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jul;78(1):26–30. doi: 10.1172/JCI112560

Transplantation of normal bone marrow into a pig with severe von Willebrand's disease.

E J Bowie, L A Solberg Jr, D N Fass, C M Johnson, G J Knutson, M L Stewart, L J Zoecklein
PMCID: PMC329526  PMID: 3088043

Abstract

Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd.

Full text

PDF
26

Images in this article

28Image
on p.28

Selected References

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

  1. Bach F. H., Day E., Bach M. L., Myhre B. A., Sengar D. P., Terasaki P. I. Histocompatibility matching. V. A comparison of typing and mixed cultures in unrelated individuals. Tissue Antigens. 1971;1(1):39–46. doi: 10.1111/j.1399-0039.1971.tb00075.x. [DOI] [PubMed] [Google Scholar]
  2. Bowie E. J., Fass D. N., Owen C. A., Jr Hemostatic effect of transfused Willebrand factor in porcine von Willebrand's disease. Similarities to the human disease. Haemostasis. 1980;9(6):352–365. doi: 10.1159/000214377. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Counts R. B., Paskell S. L., Elgee S. K. Disulfide bonds and the quaternary structure of factor VIII/von Willebrand factor. J Clin Invest. 1978 Sep;62(3):702–709. doi: 10.1172/JCI109178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fass D. N., Bowie E. J., Owen C. A., Jr, Zollman P. E. Inheritance of porcine von Willbrand's disease: study of a kindred of over 700 pigs. Blood. 1979 Apr;53(4):712–719. [PubMed] [Google Scholar]
  6. Fass D. N., Brockway W. J., Owen C. A., Jr, Bowie E. J. Factor VIII (Willebrand) antigen and ristocetin-Willebrand factor in pigs with von Willebrand's disease. Thromb Res. 1976 Mar;8(3):319–327. doi: 10.1016/0049-3848(76)90025-6. [DOI] [PubMed] [Google Scholar]
  7. Fass D. N., Knutson G. J., Bowie E. J. Porcine Willebrand factor: a population of multimers. J Lab Clin Med. 1978 Feb;91(2):307–320. [PubMed] [Google Scholar]
  8. Fernandez M. F., Ginsberg M. H., Ruggeri Z. M., Batlle F. J., Zimmerman T. S. Multimeric structure of platelet factor VIII/von Willebrand factor: the presence of larger multimers and their reassociation with thrombin-stimulated platelets. Blood. 1982 Nov;60(5):1132–1138. [PubMed] [Google Scholar]
  9. Gralnick H. R., Williams S. B., McKeown L. P., Krizek D. M., Shafer B. C., Rick M. E. Platelet von Willebrand factor: comparison with plasma von Willebrand factor. Thromb Res. 1985 Jun 15;38(6):623–633. doi: 10.1016/0049-3848(85)90205-1. [DOI] [PubMed] [Google Scholar]
  10. Griggs T. R., Webster W. P., Cooper H. A., Wagner R. H., Brinkhous K. M. Von Willebrand factor: gene dosage relationships and transfusion response in bleeder swine--a new bioassay. Proc Natl Acad Sci U S A. 1974 May;71(5):2087–2090. doi: 10.1073/pnas.71.5.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973 Nov;52(11):2757–2764. doi: 10.1172/JCI107471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of von Willebrand factor by cultured human endothelial cells. Proc Natl Acad Sci U S A. 1974 May;71(5):1906–1909. doi: 10.1073/pnas.71.5.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Katzmann J. A., Mujwid D. K., Miller R. S., Fass D. N. Monoclonal antibodies to von Willebrand's factor: reactivity with porcine and human antigens. Blood. 1981 Sep;58(3):530–536. [PubMed] [Google Scholar]
  14. Kimura A., Bowie E. J., Campbell R. J., Fass D. N. Willebrand factor in hemostasis in the in vitro bleeding time. Blood. 1979 Dec;54(6):1347–1357. [PubMed] [Google Scholar]
  15. Koutts J., Walsh P. N., Plow E. F., Fenton J. W., 2nd, Bouma B. N., Zimmerman T. S. Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin. J Clin Invest. 1978 Dec;62(6):1255–1263. doi: 10.1172/JCI109246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Mannucci P. M., Lombardi R., Bader R., Vianello L., Federici A. B., Solinas S., Mazzucconi M. G., Mariani G. Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor. Blood. 1985 Oct;66(4):796–802. [PubMed] [Google Scholar]
  18. Mannucci P. M., Pareti F. I., Holmberg L., Nilsson I. M., Ruggeri Z. M. Studies on the prolonged bleeding time in von Willebrand's disease. J Lab Clin Med. 1976 Oct;88(4):662–671. [PubMed] [Google Scholar]
  19. Nachman R. L., Jaffe E. A. Subcellular platelet factor VIII antigen and von Willebrand factor. J Exp Med. 1975 May 1;141(5):1101–1113. doi: 10.1084/jem.141.5.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nachman R., Levine R., Jaffe E. A. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest. 1977 Oct;60(4):914–921. doi: 10.1172/JCI108846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Olson J. D., Brockway W. J., Fass D. N., Bowie E. J., Mann K. G. Purification of porcine and human ristocetin-Willebrand factor. J Lab Clin Med. 1977 Jun;89(6):1278–1294. [PubMed] [Google Scholar]
  22. Olson J. D., Brockway W. J., Fass D. N., Magnuson M. A., Bowie E. J. Evaluation of ristocetin-Willebrand factor assay and ristocetin-induced platelet aggregation. Am J Clin Pathol. 1975 Feb;63(2):210–218. doi: 10.1093/ajcp/63.2.210. [DOI] [PubMed] [Google Scholar]
  23. Pineda A. A., Moore S. B., Woods J. E., Offord K. P., Zincke H., Taswell H. F. Mixed lymphocyte culture, phytohemagglutinin stimulation, and matching grade: clinical relevance in renal transplantation from living related donors. Transplantation. 1980 Feb;29(2):97–99. doi: 10.1097/00007890-198002000-00002. [DOI] [PubMed] [Google Scholar]
  24. Rudek Z., Kwiatkowska L. The possibility of detecting fetal lymphocytes in the maternal blood of the domestic pig, Sus scrofa. Cytogenet Cell Genet. 1983;36(3):580–583. doi: 10.1159/000131976. [DOI] [PubMed] [Google Scholar]
  25. Ruggeri Z. M., Zimmerman T. S. The complex multimeric composition of factor VIII/von Willebrand factor. Blood. 1981 Jun;57(6):1140–1143. [PubMed] [Google Scholar]
  26. Ruggeri Z. M., Zimmerman T. S. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest. 1980 Jun;65(6):1318–1325. doi: 10.1172/JCI109795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Slichter S. J., Counts R. B., Henderson R., Harker L. A. Preparation of cryoprecipitated factor VIII concentrates. Transfusion. 1976 Nov-Dec;16(6):616–626. doi: 10.1046/j.1537-2995.1976.16677060245.x. [DOI] [PubMed] [Google Scholar]
  28. Slot J. W., Bouma B. N., Montgomery R., Zimmerman T. S. Platelet factor VIII-related antigen: immunofluorescent localization. Thromb Res. 1978 Nov;13(5):871–881. doi: 10.1016/0049-3848(78)90192-5. [DOI] [PubMed] [Google Scholar]
  29. Sultan Y., Maisonneuve P., Angles-Cano E. Release of VIII R:Ag and VIII R:WF during thrombin and collagen induced aggregation. Thromb Res. 1979;15(3-4):415–425. doi: 10.1016/0049-3848(79)90148-8. [DOI] [PubMed] [Google Scholar]
  30. Tuddenham E. G., Lazarchick J., Hoyer L. W. Synthesis and release of factor VIII by cultured human endothelial cells. Br J Haematol. 1981 Apr;47(4):617–626. doi: 10.1111/j.1365-2141.1981.tb02691.x. [DOI] [PubMed] [Google Scholar]
  31. Wall R. T., Counts R. B., Harker L. A., Striker G. E. Binding and release of factor VIII/von Willebrand's factor by human endothelial cells. Br J Haematol. 1980 Oct;46(2):287–298. doi: 10.1111/j.1365-2141.1980.tb05968.x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Weiss H. J., Pietu G., Rabinowitz R., Girma J. P., Rogers J., Meyer D. Heterogeneous abnormalities in the multimeric structure, antigenic properties, and plasma-platelet content of factor VIII/von Willebrand factor in subtypes of classic (type I) and variant (type IIA) von Willebrand's disease. J Lab Clin Med. 1983 Mar;101(3):411–425. [PubMed] [Google Scholar]
  34. Yamamura M., Nikbin B., Hobbs J. R. Standardisation of the mixed lymphocyte reaction. J Immunol Methods. 1976;10(4):367–378. doi: 10.1016/0022-1759(76)90031-4. [DOI] [PubMed] [Google Scholar]
  35. Zucker M. B., Broekman M. J., Kaplan K. L. Factor VIII-related antigen in human blood platelets: localization and release by thrombin and collagen. J Lab Clin Med. 1979 Nov;94(5):675–682. [PubMed] [Google Scholar]
  36. van Mourik J. A., Bouma B. N., LaBruyère W. T., de Graaf S., Mochtar I. A. Factor VIII, a series of homologous oligomers and a complex of two proteins. Thromb Res. 1974 Jan;4(1):155–164. doi: 10.1016/0049-3848(74)90211-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES