Maturation of megakaryocytes and subsequent platelet release are normally regulated by a network of cytokines, including thrombopoietin and various interleukins. Because abnormal platelet production and activation have been implicated in gestational pathologies, additional pregnancy-specific cytokines may play important roles in the regulation of megakaryocytopoiesis. Consistent with this hypot...

Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain plat...

The thrombotic and hemorrhagic diathesis represents a frequent complication in myeloproliferative disorders (CMPD). They are correlated with the number of platelets, but also with their qualitative disorders, such as membrane glycoprotein changes. The latter are revealed by many platelet essays including flow-cytometry and include modified activation, secretion and aggregation patterns. The thr...

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL) despite high levels of serum TPO. Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been re...

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all...

Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze implementation current recommendations standard practice adult ITP patients, and how age may influence those changes. We included 121 patients (> 65 years, n = 54; younger individuals, 67) who initiated wi...

Mice with a null mutation in the thrombopoietin (TPO) receptor c-Mpl were generated by gene targeting. c-mpl-deficient mice developed normally but were deficient in megakaryocytes and severely thrombocytopenic. The hematocrit and numbers of mature circulating leukocytes were normal in mpT" mice, as was the distribution of morphologically identifiable precursors in hematopoietic tissues. Bone ma...