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Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on
megakaryocyte ploidy and platelet volume
L Corash, HY Chen, J Levin, G Baker, H Lu and Y Mok
We have established a murine model and techniques with which to serially
study thrombocytopoiesis after induction of experimental immune
thrombocytopenia of variable severity and duration. Bone marrow
megakaryocyte ploidy distribution was determined by using unfractionated
bone marrow, a polyclonal megakaryocyte-specific probe, and two-color,
fluorescence-activated flow cytometry. With these techniques, the modal
megakaryocyte ploidy class in normal murine bone marrow was 16N. Serial
studies of bone marrow megakaryocyte ploidy after the induction of acute,
severe thrombocytopenia (platelet count, less than 0.05 X 10(6) microL)
demonstrated no detectable change in the ploidy distribution at 12, 24, and
36 hours after the onset of thrombocytopenia. At 48 hours, the modal ploidy
class shifted from 16N to 32N, and the 64N class increased significantly (P
less than .001). The ploidy distribution returned to normal 120 hours after
the onset of thrombocytopenia. A lesser degree of thrombocytopenia
(platelet count reduction to 0.100 to 0.200 X 10(6)/microL) delayed the
modal ploidy class shift from 16N to 32N until 72 hours after the onset of
thrombocytopenia. Chronic, severe thrombocytopenia (platelet count, less
than 0.05 X 10(6)/microL for seven days) resulted in a modal ploidy class
shift from 16N to 32N during the thrombocytopenic phase and an enhanced
increase in the 64N megakaryocyte class during the recovery phase. Mean
platelet volume (MPV) was simultaneously measured on isolated total
platelet populations after induction of thrombocytopenia. MPV was
significantly increased (P less than .001) as early as eight hours after
the onset of acute, severe thrombocytopenia, 40 hours before a shift in the
ploidy distribution. Mild thrombocytopenia (platelet count reduction to
0.400 X 10(6)/microL) was not associated with a ploidy shift but did result
in a significantly increased MPV (P less than .001). These studies
demonstrate that the temporal relationship and magnitude of the effects of
thrombocytopenia upon megakaryocyte ploidy distribution are dependent upon
the degree and the duration of the thrombocytopenic stimulus and that the
effects of experimental thrombocytopenia on platelet volume and
megakaryocyte ploidy are dissociated.
Volume 70,
Issue 1,
pp. 177-185,
07/01/1987
Copyright © 1987 by The American Society of Hematology
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