An investigation of the effects of megakaryocyte ploidy and spleen size on platelet counts and platelet lifespans in two strains of mice : an animal model for studying hypersplenism

Several studies have shown that C3H mice have a modal megakaryocyte ploidy class of 32N instead of 16N that is found in all other strains of mice that have been tested [1,2], In addition to greater amounts of DNA in their megakaryocytes, C3H mice have greater platelet production, but lower platelet counts than C57BL mice. The work reported herein was undertaken to determine the cause of the mild thrombocytopenia in C3H mice. In agreement with the results of increased percent ³⁵S incorporation into platelets [3], several previous studies have shown increased platelet production in mice with elevated ploidy megakaryocytes [4-6]. Hematological studies, including platelet counts, packed cell volumes (PCV), white blood cell counts, white blood cell differential counts, and platelet lifespans, in addition to serum testosterone levels, were determined on both C3H and C57BL mice. C57BL mice were used as the control mouse strain, representing mice with 16N modal ploidy megakaryocytes. Because of the marked visual difference in the spleens of the two strains of mice, spleens were weighed and examined histologically and splenic megakaryocyte size and number were determined. In addition, tissue weights of the liver, lung parenchyma, and kidneys were determined for the two strains of mice. As a follow up, other C3H and C57BL mice were splenectomized for determination of the role of the spleen in decreasing the platelet counts of C3H mice as compared to C57BL mice. The data of the present study, in agreement with previous studies [1,4,7-9], show that C3H mice had significantly lower platelet counts (p<0.0005) and PCV's (p<0.0005) than C57BL mice. Also, an unexplained observation was that C3H mice had higher (p<0.005) serum testosterone levels than C57BL mice. In addition to having larger spleens (p<0.0005) than C57BL mice, C3H mice have spleens that contained larger and more numerous megakaryocytes (p<0.005), indicating a possible compensatory mechanism for correction of the mild thrombocytopenia. We also determined that C3H mice had a platelet lifespan of 4.8 days, which is significantly shorter (p<0.01) than the 5.7 day platelet lifespan than was found for C57BL mice. When splenectomized, platelet lifespans for C3H mice were significantly (p<0.005) longer than that found in intact C3H control mice, but in the C57BL mice, splenectomy had no effect on platelet lifespans (p>0.40). The lengthening of platelet lifespans for C3H mice by splenectomy lends credence to the hypothesis that the spleens of C3H mice were sequestering or destroying platelets at a faster rate than found in C57BL mice. Moreover, C3H mice had larger spleens with evidence of the white pulp expansion, larger lymphoid nodules, and greater amounts of periarterial lymphatic sheaths. These data support the hypothesis that hypersplenism in C3H mice results in the mild thrombocytopenia with increased platelet production compared to values from C57BL mice.