Platelets release thrombopoietin (Tpo) upon activation: another regulatoryloop in thrombocytopoiesis?

Thrombopoietin is produced at a constant rate by the liver and kidney and i s removed from the circulation upon binding and subsequent uptake via the T po receptor, c-Mpl, expressed by platelets and megakaryocytes. Apart from u ptake, this study shows that platelets can also function as a storage pool for Tpo. Upon stimulation with various platelet agonists, full-length biologically a ctive Tpo was released by platelets. Platelet fractionation experiments ind icated that this Tpo most likely is contained in the granules. When platele ts were preincubated with Tpo-peptide mimetic or truncated Tpo prior to max imal activation, a three- to fivefold increment in Tpo release was seen, wh ereas, the release of other granule proteins such as vWF-propeptide or sero tonin remained unchanged. Therefore, the Mpl agonists might compete with Mp l-bound Tpo, thereby releasing Tpo into the platelet supernatant. Intravascular release of Tpo by platelets might occur in patients with mass ive platelet activation, as occurs in patients with disseminated intravascu lar coagulation. The Tpo concentration in these patients is elevated (p <0. 01) and correlates with markers for thrombin generation, TAT complexes and F1+2 (r(p) = 0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo , which might be instrumental in subsequent stimulation of thrombocytopoies is.