The humoral regulation of megakaryocytopoiesis and platelet production in vivo.

We examined the effects of the urinary extracts from aplastic anemia (AA) patients, idiopathic thrombocytopenic purpura (ITP) patients, and normal subjects on murine megakaryocyte/platelet production in vivo and in vitro. In the first study, single doses of AA urinary protein (65%-90% ethanol precipitate) were individually injected intraperitoneally into rats and mice. Blood platelet counts in rats increased significantly 24 hours after the injection. Total megakaryocyte colony-forming units (CFU-Meg) in mouse spleens increased by 24 hours postinjection, peaked at 48 hours and returned to normal levels at 96 hours. Changes in the number of megakaryocyte colonies showed similar patterns of increasing, peaking and returning to normal levels postinjection. In the second study, we compared the effects of some urinary extracts on murine megakaryocyte/platelet production. These observations provided the evidence that AA urinary extracts contain a factor that directly stimulates megakaryocyte progenitor cell proliferation in mouse spleen in vivo as well as the release of platelets from megakaryocytes, and ITP urinary extracts do not contain increased levels of Meg-CSF and/or some other factor that directly stimulates CFU-Meg in vivo, and the decreased blood platelet mass that is clinically characteristic of ITP is not a primary in vivo determinant of the elaboration of these factors.