title: Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates.
abstract: Neonatal thrombocytopenia affects 22-35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York;
authors.forename: Mudit
authors.initials: M
authors.lastname: Kulshrestha
authors.affiliation: Division of Newborn Medicine, Children's Hospital Boston, Boston, Massachusetts;
authors.forename: Martha
authors.initials: M
authors.lastname: Sola-Visner
authors.affiliation: Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: John A
authors.initials: JA
authors.lastname: Widness
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, Iowa.
authors.forename: Peter
authors.initials: P
authors.lastname: Veng-Pedersen
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York; dmager@buffalo.edu.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Mager
mesh_terms: D001792:Blood Platelets; D016638:Critical Illness; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D019102:Infant, Very Low Birth Weight / Q000097:blood; D007700:Kinetics; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010641:Phenotype; D018962:Phlebotomy; D010976:Platelet Count; D017713:Platelet Transfusion; D013921:Thrombocytopenia / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D016896:Treatment Outcome
keywords: immature platelet fraction; neonatal thrombocytopenia; platelets; transit compartment model