Postirradiation thrombocytopoiesis: suppression, recovery, compensatory states, and macromegakaryocytosis

Two unusual features of the regulation of megakaryocytopoiesis have been found in irradiated mice. The first is that the response to thrombocytopenia loses its specificity for thrombocytopoiesis when the thrombocytopenia is induced at the time of exposure to sublethal doses of radiation. Under these conditions, there is stimulation of both thrombocytopoiesis and erythropoiesis. The second unusual feature is that a completely or partially compensated hypomegakaryocytic state may develop after "recovery" from the earlier severe postirradiation myelodepression. Occurrence of this condition is not dependent on the presence or absence of the spleen. It is characterized by a dissociation between platelet and megakaryocyte numbers, with platelets being relatively higher. There is an associated increase in mean megakaryocyte size. Both the megakaryocytopenia and macromegakaryocytosis are due to a deficiency of smaller megakaryocytes in the marrow. The postirradiation abnormality of megakaryocyte size distribution can not be accounted for by irradiation-induced abnormalities of either hemopoietic or stromal cells. The degree of megakaryocytic macrocytosis does not correlate with the platelet or megakaryocyte count after recovery from sublethal irradiation or after recovery from lethal irradiation and rescue with normal bone marrow cells. Megakaryocytic macrocytosis, as identified by an increase in average size of mature cells, occurs in response to thrombocytopenia and in several hypomegakaryocytic states in which thrombocytopenia is absent or is mild in degree. Comparison of size distribution curves, analysis of sizes of immature megakaryocytes, and determination of the stability of the megakaryocyte count indicate that different mechanisms probably prevail. The presence or absence of thrombopoietin or other megakaryocyte growth factors in these conditions may provide clues about the mechanisms.