Significance Thrombocytopenia is a common hematologic problem among neonates and of significant clinical importance because of the increased incidence of intracranial hemorrhage and morbidity in thrombocytopenic neonates. Although commonly observed, the pathophysiology 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 some groups of thrombocytopenic adults have been shown to respond favorably to the administration of PEG-rHuMGDF, the objective of this study was to determine the safety when administered to newborn rhesus monkeys. Results Eight monkeys were treated subcutaneously with 0, 0.25, 1, or 2.5 5g/kg PEG-rHuMGDF once daily for seven days. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates prior to and post-treatment. All rhesus neonates showed normal growth parameters during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration was shown to occur at 3 hours, and the half-life was 8.4 to 13 hours. Platelet counts in the treated neonates began to rise on day 6, peaked on day 11, and returned to baseline by day 23. The two highest doses generated an 8- to 12-fold increase in platelets, while those treated with 0.25 5g/kg had a 6-fold increase. All other hematologic parameters measured were unaffected, but induced an increase in the megakaryocyte progenitors in bone marrow. Thus, newborn monkeys responded to doses of PEG-rHuMGDF, and responses were similar to or less than those that were effective in adult animals, without any evidence of adverse effects. Future Directions We will continue to explore safe and efficacious alternatives to platelet transfusions for the management of thrombocytopenia in human neonates. KEY WORDS neonate, monkey, thrombocytopenia, platelets, thrombopoietin FUNDING NIH Grant HL55175, Private Sources

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-38
Application #
6116660
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Comrie, Alison E; Gray, Daniel T; Smith, Anne C et al. (2018) Different macaque models of cognitive aging exhibit task-dependent behavioral disparities. Behav Brain Res 344:110-119
Day, George Q; Ng, Jillian; Oldt, Robert F et al. (2018) DNA-based Determination of Ancestry in Cynomolgus Macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci 57:432-442
Carroll, Timothy D; Jegaskanda, Sinthujan; Matzinger, Shannon R et al. (2018) A Lipid/DNA Adjuvant-Inactivated Influenza Virus Vaccine Protects Rhesus Macaques From Uncontrolled Virus Replication After Heterosubtypic Influenza A Virus Challenge. J Infect Dis 218:856-867
Midic, Uros; VandeVoort, Catherine A; Latham, Keith E (2018) Determination of single embryo sex in Macaca mulatta and Mus musculus RNA-Seq transcriptome profiles. Physiol Genomics 50:628-635
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Ciupe, Stanca M; Miller, Christopher J; Forde, Jonathan E (2018) A Bistable Switch in Virus Dynamics Can Explain the Differences in Disease Outcome Following SIV Infections in Rhesus Macaques. Front Microbiol 9:1216
Feng, Jun-Feng; Liu, Jing; Zhang, Lei et al. (2017) Electrical Guidance of Human Stem Cells in the Rat Brain. Stem Cell Reports 9:177-189
Han, Pengcheng; Nielsen, Megan; Song, Melissa et al. (2017) The Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques. Front Aging Neurosci 9:180
Pittet, Florent; Johnson, Crystal; Hinde, Katie (2017) Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta). Am J Phys Anthropol 164:457-476
Kyle, Colin T; Stokes, Jared; Bennett, Jeffrey et al. (2017) Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus: Preservation of subfield volumes in aging. Hippocampus :

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