A PRIMARY PRODUCTION DEFICIT IN THE THROMBOCYTOPENIA OF EQUINE INFECTIOUS-ANEMIA

The purpose of this study was to identify the mechanisms responsible f or 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 experimentall y infected with EIAV. Levels of viremia and a number of clinical and h ematologic 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 plat elets, measured by metabolic incorporation of radioactive label, was s ignificantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured b y Cr-51 labeling, also declined following infection in both SCID and i mmunocompetent foals: 51 and 68%, respectively, relative to the preinf ection life spans. The difference between immunocompetent and immunode ficient foals was not statistically significant. The number of megakar yocytes (MK) per square millimeter of bone marrow determined by digiti zing morphometry, was not significantly altered in either SCID or immu nocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per u nit area increased, but the elevation was not statistically significan t. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fi brin degradation products, and onestep prothombin time) remained norma l until after platelet numbers had declined significantly, arguing aga inst an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally thro ugh an indirect, noncytocidal suppressive effect on platelet productio n, the mechanism of which is unknown. A shortening of platelet life sp an apparently contributes moderately to the platelet deficit as well. The shortening of platelet life span is multifactorial in origin, incl uding both mechanisms that depend on an active immune response and tho se that do not.