Polyploidization of Megakaryocytes in Normal Humans, in Patients with Idiopathic Thrombocytopenia and with Pernicious Anaemia

Abstract

Summary. Polyploidization of human megakaryocytes was studied in bone marrow aspirates from three normal individuals, three patients with idiopathic thrombocytopenic purpura (ITP) and three patients with pernicious anaemia (PA). The cells were labelled in vitro with tritiated thymidine and analysed by a combined cytophotometric and autoradiographic method. Cells were divided into types I, II and III. Normal megakaryocytes showed ploidy stages from 4c to 32c, the 4c stage occurring only in type I. The labelling indices showed that in normal megakaryocytes polyploidization takes place in type I and II and not in type III cells. This study provided evidence for alternation of DNA synthesis and rest periods. It is postulated that rhythmical polyploidization in megakaryocytopoiesis takes place. The progressive increase in the proportion of cells in successive resting periods (G‐phases) suggests that high ploidy cells have longer resting periods than low ploidy cells. In ITP, megakaryocyte morphology, labelling indices and distribution of DNA content were normal. Assuming a normal ploidy composition in ITP, the megakaryocytic hyperplasia observed in typical cases may be explained by an increased influx from the unrecognizable progenitor cell. In PA, an arrest of megakaryocytic DNA synthesis was observed comparable to that found in megaloblastic erythropoiesis.

Micromegakaryocytes in Human Bone Marrow

“…This is true for cell size, number and shape of nu clei and nuclear/cytoplasmic ratio. The DNA content varies between 4 and 32 c with the majority of mature cells at 16 or 32 c [15]. The diagnostic significance of mor phological aberrations of MK is therefore commonly regarded as less important than 'specific' abnormal morphological patterns in the erythroid and granulopoietic series.…”

“…During the maturation process they undergo endomitotic division and become polyploid and large in size [12,15]. In some haematological dis eases, the MK show typical morphological abnormalities: hyperlobulated nuclei occur in pernicious anaemia and especially large MK are found in polycythaemia vera.…”

Megakaryocyte Polyploidization in May-Hegglin Anomaly

“…The mode of polyploidization has been the subject of many in vestigations during the last years. Evidence has been provided for alterna tion of DNA synthesis and periods of rest suggesting a rhythmical polyploi dization [11]. It may be assumed that the pattern of polyploidization influences platelet maturation and release.…”

“…The smallest mega karyocytes with more than 12 grains and megakaryocytes double that size with more than 24 grains were designated as labeled. More details of the combined cytophotometric and autoradiographic technique were described earlier [11].…”

“…Megakaryocytes showing no basophilia, but strong azurophilic granula tion of the cytoplasm and a low nuclear-cytoplasmic ratio. Since the nuclear size is well correlated to the DNA content [11], but not to the state of maturation, this cri terion of cell differentiation was discarded.…”