This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Thrombocytopenia is one of the most common hematologic problems among patients in Neonatal Intensive Care Units (NICU), affecting 20-35% of NICU patients. In thrombocytopenic adults, the administration of recombinant thrombopoietin (rTpo) is being investigated as an alternative to platelet transfusions. Results from our previous in vitro and in vivo studies have suggested that rTpo administration could be an effective therapy for thrombocytopenic neonates. Since rTpo does not increase the platelet count until 4 to 6 days after starting therapy, however, the only appropriate candidates would be neonates whose thrombocytopenia is severe and prolonged. Unfortunately, the application of new therapies to thrombocytopenic neonates has been significantly hampered by our lack of understanding of even the basic kinetic mechanisms responsible for their thrombocytopenias (platelet destruction vs. decreased platelet production). With the development of rTpo, there is now a pressing need to clarify these mechanisms. With this in mind, we designed this study to; (1) identify the kinetic mechanisms responsible for severe and prolonged thrombocytopenia in NICU patients, and (2) establish the correlation between peripheral blood and bone marrow indicators of thrombopoiesis in thrombocytopenic neonates. To accomplish this, we will use techniques specifically developed for the study of megakaryocyte mass and ploidy in the bone marrow of neonates, and will correlate these with newly developed indirect measures of thrombopoiesis (i.e. reticulated platelet counts, serum Tpo concentrations, and circulating megakaryocyte progenitors).
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