Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/123438
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: A model for studying the hemostatic consumption or destruction of platelets
Author: Dowling, M.
Josefsson, E.
Henley, K.
Kile, B.
Hodgkin, P.
Citation: PLoS One, 2013; 8(3):e57783-1-e57783-14
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Editor: Yates, A.J.
Statement of
Responsibility: 
Mark R. Dowling, Emma C. Josefsson, Katya J. Henley, Benjamin T. Kile, Philip D. Hodgkin
Abstract: A fundamental issue in understanding homeostasis of the hematopoietic system is to what extent intrinsic and extrinsic factors regulate cell fate. We recently revisited this issue for the case of blood platelets and concluded that platelet life span is largely regulated by internal factors, in contrast to the long-held view that accumulated damage from the environment triggers clearance. However, it is known that in humans there is an ongoing fixed requirement for platelets to maintain hemostasis and prevent bleeding; hence a proportion of platelets may be consumed in such processes before the end of their natural life span. Whether it is possible to detect this random loss of platelets in normal individuals at steady-state is unknown. To address this question, we have developed a mathematical model that independently incorporates age-independent random loss and age-dependent natural senescent clearance. By fitting to population survival curves, we illustrate the application of the model in quantifying the fixed requirement for platelets to maintain hemostasis in mice, and discuss the relationship with previous work in humans. Our results suggest a higher requirement for platelets in mice than in humans, however experimental uncertainty in the data limits our ability to constrain this quantity. We then explored the relationship between experimental uncertainty and parameter constraint using simulated data. We conclude that in order to provide useful constraint on the random loss fraction the standard error in the mean of the data must be reduced substantially, either through improving experimental uncertainty or increasing the number of experimental replicates to impractical levels. Finally we find that parameter constraint is improved at higher values of the random loss fraction; thus the model find utility in situations where the random loss fraction is expected to be high, for example during active bleeding or some types of thrombocytopenia.
Keywords: Blood Platelet hemostasis
Rights: © 2013 Dowling et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0057783
Grant ID: http://purl.org/au-research/grants/nhmrc/516725
http://purl.org/au-research/grants/nhmrc/575535
http://purl.org/au-research/grants/nhmrc/1010654
http://purl.org/au-research/grants/nhmrc/1016647
http://purl.org/au-research/grants/nhmrc/361646
Appears in Collections:Aurora harvest 8
Medicine publications

Files in This Item:
File Description SizeFormat 
hdl_123438.pdfPublished Version787.67 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.