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Dynamic Model of Platelet Lifespan in Adult and Newborn Mice
Author(s) -
AitOudhia Sihem,
Mager Donald E.,
Liu ZhiJian,
VengPedersen Peter,
SolaVisner Martha
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb535
Subject(s) - platelet , animal model , population , flow cytometry , andrology , transit time , medicine , biology , immunology , engineering , environmental health , transport engineering
Objective To develop a mathematical model of platelet survival (PLT‐S) in newborn and adult mice and identify factors controlling differences in PLT lifespan (PLT‐L) between these groups. Methods PLT‐S profiles were obtained from 23 mice (16 newborn and 7 adult) by measuring biotinylate labeled (LBL) and total PLT count (PLTtot=LBL+non‐LBL) using flow cytometry. Non‐LBL endogenous PLT were described with three transit‐compartments and a zero‐order production rate. In newborns, PLT‐L model parameters were time‐dependent and approached the constant values in adults. Biotinylation efficiency was assumed complete, and LBL and PLTtot were simultaneously analyzed using population‐based modeling. Between‐animal variability (BAV) was estimated. Results The final model well described LBL and PLTtot in all animals. Parameters were estimated with good precision. At time=0, PLT‐L was fitted at 4.92 and 3.76 days in newborn and adult mice. After 14 days, PLT‐L for all animals was constant at 3.76 days. PLT production was estimated to be similar between groups at 12.4 and 11.9 (10 3 cells/μL/h). BAV for PLT‐L parameters were below 30%. Conclusion Neonatal PLT‐L is greater than adults by 1 day, but PLT production rates are similar. Unlike traditional models assuming steady‐state, our dynamic PLT‐L model captured data well and allowed for accurate estimation of factors governing PLT counts. Grants HL046925 & GM 57980.