Significance Thrombocytopenia is a common hematologic problem among patients in Neonatal Intensive Care Units (NICU) and of significant clinical importance because of the increased incidence of intracranial hemorrhage and morbidity in thrombocytopenic neonates. Although commonly observed, the pathophysiology in preterm and term neonates is poorly understood. Objectives Very little is known about the role of thrombopoietin (Tpo), a recently discovered physiologic stimulator of platelet production, in thrombocytopenia. Because it is inherently difficult to conduct studies with very small, very ill human neonates, a fetal/neonatal monkey model is being used to study Tpo ontogeny and to explore new methods for treating thrombocytopenias frequently observed in growth restricted neonates. Results Initial studies have focused on the assessment of endogenous Tpo in rhesus monkeys, and whether human recombinant Tpo (rTpo) can be quantified reproducibly in rhesus plasma. Fetal and maternal (second trimester to term) and neonatal (birth to 3 months) plasma samples were assayed with the use of a commercial ELISA. Circulating Tpo levels in the dam ranged from 11-124 pg/mL (mean 63133 pg/mL) and fetal/neonatal samples from 25-123 pg/mL (mean 87130 pg/mL). No correlation was found between plasma Tpo and gestational or postnatal age. Two ?spiking? studies were conducted with adult and neonatal rhesus samples, and full recovery of added rTpo was found (77-118% of predicted values). These findings indicate that circulating endogenous Tpo levels in the rhesus monkey are similar to findings in humans, and support the appropriateness of the rhesus monkey for studying questions related to the role of Tpo in megakaryopoiesis and thrombocytopenia. Future Directions Newborn rhesus monkeys will be treated with rTpo (pegylated megakaryocyte growth and development factor [MGDF]) in order to determine safety and efficacy. KEYWORDS neonate, thrombocytopenia, hematopoiesis, growth restriction

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-37
Application #
6277901
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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