Megakaryocytopoiesis in the rat: response to thrombocytopenia induced by exchange transfusion

Abstract

We have studied the megakaryocytopoietic response in rats to acute thrombocytopenia induced by exchange transfusion of platelet-poor blood. Our analysis included serial determinations of peripheral blood counts, the size and number of megakaryocytes in sections of humeral marrow, the numbers of megakaryocytic (CFU-Meg) and granulocyte-macrophage (CFU-GM) colony-forming cells in marrow and spleen, and the proportion of CFU-Meg and CFU-GM in DNA synthesis. With exchange transfusion, the platelet count fell to 11% of the control value (101,000 +/- 49,000/mm3; mean +/- SD) and returned to normal by day 3; rebound thrombocytosis (peak 1,720,000 +/- 246,000/mm3) was observed on days 4 and 5. The average size of marrow megakaryocytes increased significantly on days 2 and 3 compared with normal (p less than 0.01), but the numbers of recognizable megakaryocytes did not change through day 5. The numbers of splenic CFU-Meg and CFU-GM increased significantly (p less than 0.05) on days 2-4 and on day 2, respectively, after the exchange; however, the numbers of marrow progenitors, which account for over 95% of total body progenitors, remained unchanged throughout the duration of the study. The proportion of CFU-Meg in DNA synthesis (mean +/- SD) increased from a baseline value of 17% +/- 4% to 33% +/- 11% (p less than 0.02) and 35% +/- 6% (p less than 0.001) on days 1 and 2, respectively, and returned to control values thereafter. There were no changes in the cell cycle activity of CFU-GM. Thus, acute selective thrombocytopenia induced by exchange transfusion causes an enlargement of marrow megakaryocytes and an increase in the fraction of CFU-Meg in cell cycle. These changes, occurring in the absence of immunologically mediated events, are the direct result of lowered platelet count.