Effects of Thrombocytopenia on Megakaryocytopoiesis

Abstract

Summary. Megakaryocytopoiesis was studied in rats made thrombocytopenic by daily injections of platelet‐specific antiserum. Tritiated thymidine was injected 24 hours after the first antiserum and rats were killed at intervals up to 72 hours after the thymidine. Megakaryocyte number and mitotic index were determined on sections of bone marrow; the labelling index (per cent of cells labelled) and frequency of megakaryocytes in morphologic compartments were determined in autoradiograms of marrow smears. Thrombocytopenia caused an increase in the numbers of megakaryocytes, beginning about a day after the first injection of antiserum, with young forms becoming more frequent in the recognizable population. At about the same time, there was an increase in the mitotic index (endomitosis) of megakaryocytes. All of these results indicated an increased influx of cells into the recognizable megakaryocyte population. Later the frequency of older forms increased, revealing that a cohort of cells was passing through the maturation process. The changes in labelling index suggested that megakaryocytes may mature more rapidly in thrombocytopenic rats than in controls. The results suggest that a regulatory agent may act on a diploid precursor cell in responding to the thrombocytopenic state.

Thrombopoietin Activity in Mice Following Immune-Induced Thrombocytopenia

“…If one assumes that thrombopoietin accelerates thombocytopoiesis by acting at the level of the morphologically unidentified megakaryocyte precursor cell compartment (pluripotential or polyploid) and that the cell generation time in this compartment is approximately the same as that for the proliferating megakaryocyte compartment (9.5 h) [9], then one might expect to observe increase levels of thrombopoietin preceding a 'reactive' megakaryocytosis. Such a megakaryocytosis occurs within 24-72 h after the induction of thrombocytopenia [4,7,10].…”

A Role for Changes in Platelet Production in the Cause of Acute Coronary Syndromes

“…41 Platelets produced under conditions of stimulated platelet production, called "stress" platelets by Penington et al 38 show an increase in the MPV compared with normal circulating platelets. 37,38,42,43 There is strong evidence indicating that MPV is an important biological variable 44 and that large platelets have a higher thrombotic potential. Karpatkin et al 8,23,45,46 and Corash et al 47 have demonstrated that large platelets are metabolically and enzymatically more active than small platelets as assessed by ex vivo aggregometry.…”

Alteration of Rat Bone Marrow Megakaryocytes Following Administration of Cytosine Arabinoside, Daunomycin and Hydroxyurea

“…The relatively few M-I cells found on the 6th day following the last injection of the cytotoxic agents may still be due to the drug-induced retardation of the proliferation of the megakaryo cyte precursors, although the low M-I and high M-I 11 percentage found at that stage following Ara-C and D administration might reflect a shortened megakaryocyte maturation time, as observed by O d ell et al [12] after thrombocytopenic episodes in rats following administration of antiplatelet serum. The latter explanation would be compatible with the rise in the pla telet count observed at this stage in the Ara-C-treated and D-treated rats.…”