Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia

The hypothesis that in immune thrombocytopenia, platelet antibody may not only cause destruction of the circulating platelets but also depress platelet production by injuring the megakaryocytes of the bone marrow, was tested experimentally.

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

Profoundly altered patterns of megakaryocytopoiesis were found in the rats in which thrombocytopenia was produced by the antiplatelet serum. The data indicated a severely impaired and depressed megakaryocyte maturation and, possibly, destruction of some of the megakaryocytes during their maturation process. In the rats in which the platelet level was maintained low by repeated thrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. No difference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced an injurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was the result of both increased platelet destruction and defective platelet production.