Detection of thrombopoietic activity in plasma by stimulation of suppressed thrombopoiesis.

Rabbits in which thrombocytosis had been produced by five daily transfusions of platelet concentrates had suppressed endogenous thrombopoiesis, as reflected by decreased incorporation of selenomethionine-(75)Se ((75)SeM) into the circulating platelet mass. Rabbits in which endogenous thrombopoiesis had been suppressed by transfusion-induced thrombocytosis were used to detect thrombopoietic activity in rabbit plasma. Thrombopoietic activity was demonstrated in the plasma of both normal and thrombocytopenic donor rabbits. A dose response relationship was observed between the incorporation of (75)SeM into platelets and the dose of plasma administered. Infusion of 20-150 ml of plasma from thrombocytopenic donors increased the incorporation of (75)SeM into platelets from 52 to 107% above control values. A dose response effect also was seen after infusion of normal plasma, but normal plasma produced less effect than comparable doses of plasma from thrombocytopenic donors. Rabbits with transfusion-induced thrombocytosis appear to be more sensitive assay animals for the detection of thrombopoietic activity than animals with normal platelet counts. Changes in the rate of appearance and levels of (75)SeM may primarily indicate changes in platelet protein or platelet size and are apparently more sensitive indicators of the state of thrombopoiesis than are alterations in the numbers of circulating platelets. The results strongly support the concept of a humoral agent, i.e. thrombopoietin, that acts on megakaryocytes to regulate platelet production.