Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Nov;70(11):7842–7850. doi: 10.1128/jvi.70.11.7842-7850.1996

A primary production deficit in the thrombocytopenia of equine infectious anemia.

T B Crawford 1, K J Wardrop 1, S J Tornquist 1, E Reilich 1, K M Meyers 1, T C McGuire 1
PMCID: PMC190855  PMID: 8892906

Abstract

The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompetent foals. Production of platelets, measured by metabolic incorporation of radioactive label, was significantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured by 51Cr labeling, also declined following infection in both SCID and immunocompetent foals: 51 and 68%, respectively, relative to the preinfection life spans. The difference between immunocompetent and immunodeficient foals was not statistically significant. The number of megakaryocytes (MK) per square millimeter of bone marrow, determined by digitizing morphometry, was not significantly altered in either SCID or immunocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per unit area increased, but the elevation was not statistically significant. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fibrin degradation products, and one-step prothombin time) remained normal until after platelet numbers had declined significantly, arguing against an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally through an indirect, noncytocidal suppressive effect on platelet production, the mechanism of which is unknown. A shortening of platelet life span apparently contributes moderately to the platelet deficit as well. The shortening of platelet life span is multifactorial in origin, including both mechanisms that depend on an active immune response and those that do not.

Full Text

The Full Text of this article is available as a PDF (236.6 KB).

Selected References

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

  1. Ballem P. J., Belzberg A., Devine D. V., Lyster D., Spruston B., Chambers H., Doubroff P., Mikulash K. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med. 1992 Dec 17;327(25):1779–1784. doi: 10.1056/NEJM199212173272503. [DOI] [PubMed] [Google Scholar]
  2. Boudreaux M. K., Weiss R. C., Toivio-Kinnucan M., Spano J. S. Potentiation of platelet responses in vitro by feline infectious peritonitis virus. Vet Pathol. 1990 Jul;27(4):261–268. doi: 10.1177/030098589002700407. [DOI] [PubMed] [Google Scholar]
  3. Bull B. S., Schneiderman M. A., Brecher G. Platelet counts with the Coulter counter. Am J Clin Pathol. 1965 Dec;44(6):678–688. doi: 10.1093/ajcp/44.6.678. [DOI] [PubMed] [Google Scholar]
  4. Clabough D. L., Gebhard D., Flaherty M. T., Whetter L. E., Perry S. T., Coggins L., Fuller F. J. Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus. J Virol. 1991 Nov;65(11):6242–6251. doi: 10.1128/jvi.65.11.6242-6251.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coyne C. P., Kelly A. B., Hornof W. J., O'Brien T. R., Philp M. S., Lamb J. F. Radiolabeling of equine platelets in plasma with 111In-(2-mercaptopyridine-N-oxide) and their in vivo survival. Am J Vet Res. 1987 Mar;48(3):385–391. [PubMed] [Google Scholar]
  6. DALTON A. J., LAW L. W., MOLONEY J. B., MANAKER R. A. An electron microscopic study of a series of murine lymphoid neoplasms. J Natl Cancer Inst. 1961 Oct;27:747–791. [PubMed] [Google Scholar]
  7. Dassin E., Najean Y. The use of 75Se-methionine as a tracer of thrombocytopoiesis. I. In vivo incorporation of the tracer into platelet proteins: a biochemical study. Acta Haematol. 1979;61(2):61–67. doi: 10.1159/000207633. [DOI] [PubMed] [Google Scholar]
  8. Hymes K. B., Greene J. B., Karpatkin S. The effect of azidothymidine on HIV-related thrombocytopenia. N Engl J Med. 1988 Feb 25;318(8):516–517. doi: 10.1056/NEJM198802253180812. [DOI] [PubMed] [Google Scholar]
  9. Issel C. J., Coggins L. Equine infectious anemia: current knowledge. J Am Vet Med Assoc. 1979 Apr 1;174(7):727–733. [PubMed] [Google Scholar]
  10. Karpatkin S., Nardi M., Lennette E. T., Byrne B., Poiesz B. Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9763–9767. doi: 10.1073/pnas.85.24.9763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McDonald T. P., Cottrell M., Clift R. Effects of short-term hypoxia on platelet counts of mice. Blood. 1978 Jan;51(1):165–175. [PubMed] [Google Scholar]
  12. McGuire T. C., Henson J. B., Quist S. E. Impaired bone marrow response in equine infectious anemia. Am J Vet Res. 1969 Dec;30(12):2099–2104. [PubMed] [Google Scholar]
  13. Murphy E. A., Francis M. E. The estimation of blood platelet survival. II. The multiple hit model. Thromb Diath Haemorrh. 1971;25(1):53–80. [PubMed] [Google Scholar]
  14. Nash R. A., Burstein S. A., Storb R., Yang W., Abrams K., Appelbaum F. R., Boone T., Deeg H. J., Durack L. D., Schuening F. G. Thrombocytopenia in dogs induced by granulocyte-macrophage colony-stimulating factor: increased destruction of circulating platelets. Blood. 1995 Sep 1;86(5):1765–1775. [PubMed] [Google Scholar]
  15. Nieuwenhuis H. K., Sixma J. J. Thrombocytopenia and the neglected megakaryocyte. N Engl J Med. 1992 Dec 17;327(25):1812–1813. doi: 10.1056/NEJM199212173272510. [DOI] [PubMed] [Google Scholar]
  16. O'Rourke K., Perryman L. E., McGuire T. C. Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. J Gen Virol. 1988 Mar;69(Pt 3):667–674. doi: 10.1099/0022-1317-69-3-667. [DOI] [PubMed] [Google Scholar]
  17. Perryman L. E., McGuire T. C., Crawford T. B. Maintenance of foals with combined immunodeficiency: causes and control of secondary infections. Am J Vet Res. 1978 Jun;39(6):1043–1047. [PubMed] [Google Scholar]
  18. Perryman L. E., O'Rourke K. I., McGuire T. C. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J Virol. 1988 Aug;62(8):3073–3076. doi: 10.1128/jvi.62.8.3073-3076.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scadden D. T., Zon L. I., Groopman J. E. Pathophysiology and management of HIV-associated hematologic disorders. Blood. 1989 Oct;74(5):1455–1463. [PubMed] [Google Scholar]
  20. Sentsui H., Kono Y. Complement-mediated hemolysis of horse erythrocytes treated with equine infectious anemia virus. Arch Virol. 1987;95(1-2):53–66. doi: 10.1007/BF01311334. [DOI] [PubMed] [Google Scholar]
  21. Snyder E. L., Moroff G., Simon T., Heaton A. Recommended methods for conducting radiolabeled platelet survival studies. Transfusion. 1986 Jan-Feb;26(1):37–42. doi: 10.1046/j.1537-2995.1986.26186124029.x. [DOI] [PubMed] [Google Scholar]
  22. Stephens R. M., Casey J. W., Rice N. R. Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science. 1986 Feb 7;231(4738):589–594. doi: 10.1126/science.3003905. [DOI] [PubMed] [Google Scholar]
  23. Swardson C. J., Kociba G. J., Perryman L. E. Effects of equine infectious anemia virus on hematopoietic progenitors in vitro. Am J Vet Res. 1992 Jul;53(7):1176–1179. [PubMed] [Google Scholar]
  24. Walsh C. M., Nardi M. A., Karpatkin S. On the mechanism of thrombocytopenic purpura in sexually active homosexual men. N Engl J Med. 1984 Sep 6;311(10):635–639. doi: 10.1056/NEJM198409063111004. [DOI] [PubMed] [Google Scholar]
  25. Wardrop K. J., Baszler T. V., Reilich E., Crawford T. B. A morphometric study of bone marrow megakaryocytes in foals infected with equine infectious anemia virus. Vet Pathol. 1996 Mar;33(2):222–227. doi: 10.1177/030098589603300212. [DOI] [PubMed] [Google Scholar]
  26. Zauli G., Re M. C., Davis B., Sen L., Visani G., Gugliotta L., Furlini G., La Placa M. Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals. Blood. 1992 May 15;79(10):2680–2687. [PubMed] [Google Scholar]
  27. Zucker-Franklin D. The effect of viral infections on platelets and megakaryocytes. Semin Hematol. 1994 Oct;31(4):329–337. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES