THE EFFECTS OF LEUKEMIA INHIBITORY FACTOR ON PLATELET-FUNCTION

Leukaemia inhibitory factor (LIF) is able to promote megakaryocytopoiesis in vitro and elevate platelet counts in vivo, and is a potential new therapeutic agent for the treatment of thrombocytopenia. To determine whether platelets released under conditions of LIF-stimulated megakaryocytopoiesis have intact function, we compared aggregation responses of platelets from mice with constitutively elevated LIF levels (FD/LIF mice) and mice injected with recombinant murine LIF (rmLIF mice) with their respective control mice. We report that ex vivo platelet aggregability and thromboxane B2 release were intact in the LIF-treated mice, and were significantly enhanced in some situations. LIF-treated mice also had significantly increased platelet counts (FD/LIF mice: 1302 +/- 173 x 10(9)/l compared to 1012 +/- 99 x 10(9)/l for FD mice, rmLIF mice: 1460 +/- 193 x 10(9)/l compared to 985 +/- 67 x 10(9)/l for FCS/NS mice), increased platelet volumes and elevated plasma fibrinogen and calcium levels. The platelet hyperreactivity seen in the LIF-treated mice is likely to reflect the larger platelet volumes and/or the effect of plasma components such as fibrinogen, elevated levels of which were due to the concomitant action of LIF as a stimulant of acute phase protein synthesis.