Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia

The hypothesis that in immune thrombocytopenia, platelet antibody maynot only cause destruction of the circulating platelets but also depress plateletproduction by injuring the megakaryocytes of the bone marrow, was testedexperimentally.

Sustained thrombocytopenia was produced in rats by titrated injections ofa potent heteroimmune antiplatelet serum and megakaryocytopoiesis wasthen studied by the use of tritiated thymidine and bone marrow autoradiography. Rats in which the platelet count was maintained at a lower thannormal level by repeated thrombocytophereses, and other rats injected withplatelet antiserum previously absorbed with rat platelets, served as controls.

Profoundly altered patterns of megakaryocytopoiesis were found in the ratsin which thrombocytopenia was produced by the antiplatelet serum. The dataindicated a severely impaired and depressed megakaryocyte maturation and,possibly, destruction of some of the megakaryocytes during their maturationprocess. In the rats in which the platelet level was maintained low by repeatedthrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. Nodifference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced aninjurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was theresult of both increased platelet destruction and defective platelet production.

Submitted on November 22, 1968 Accepted on October 3, 1969