Summary
Thrombopoietin modulates the response of platelets to several agonists and, on the
other hand, those agonists can be released following irradiation. Thus, we have determined
the effects of thrombopoietin, on its own and in combination with ticlopidine, an
anti-platelet drug, on platelet activation, thrombosis formation and survival of irradiated
C57BL6/J mice. Administration of thrombopoietin 2 h after 9 Gy total body irradiation
increased the 125I-fibrin deposition in mouse tissues and accelerated platelet consumption as revealed
by an enhanced drop in platelet counts. Additionally, the number of activated platelets,
i.e. those expressing P-selectin on their membrane, was higher in thrombopoietin-treated
mice as compared to the placebo group, regardless ex vivo stimulation with agonists. These effects of thrombo-poietin on platelet activation
and consumption were reduced when mice were pretreated with ticlopidine. The combination
of ticlopidine with thrombopoietin almost fully promoted 180-day survival, reaching
the same efficacy as bone marrow transplantation, while only 30% of the mice treated
with thrombopoietin alone survived. In summary, thrombopoietin induces long term-mortality
of irradiated mice probably through platelet-mediated thrombosis and thus, ticlopidine
efficiently counteracts these adverse effects of thrombopoietin.
Keywords
Thrombopoietin - irradiation - thrombosis - platelet - ticlopidine
