title: Neonatal mice with necrotizing enterocolitis-like injury develop thrombocytopenia despite increased megakaryopoiesis.
abstract: BACKGROUND
  Thrombocytopenia is frequently encountered in infants with necrotizing enterocolitis (NEC). To develop a preclinical model of NEC-related thrombocytopenia, we measured serial platelet counts in 10-d-old (P10) mouse pups with trinitrobenzene sulfonic acid (TNBS)-induced NEC-like injury. We also measured platelet volume indices, immature platelet fraction (IPF), and megakaryocyte number/ploidy in these animals.
  
  
  METHODS
  Platelet counts, platelet volume indices, and IPF were measured in control (N = 65) and TNBS-treated pups (N = 104) using an automated hematology analyzer. Bone marrow megakaryocyte number, ploidy and CD41 expression were measured by flow cytometry. These findings were confirmed in a small cohort of P3 mice with NEC-like injury.
  
  
  RESULTS
  Murine pups with TNBS-mediated NEC-like injury developed thrombocytopenia at 15-24 h after exposure to TNBS. Intestinal injury was associated with increased platelet volume indices (mean platelet volume, platelet-to-large cell ratio, and platelet distribution width), and IPF, indicating increased thrombopoiesis. These mice also showed increased megakaryocyte number, ploidy, and CD41 expression, indicating increased megakaryocyte differentiation.
  
  
  CONCLUSIONS
  Similar to human NEC, murine NEC-like injury was also associated with decreased platelet counts. There was evidence of increased megakaryocyte differentiation and thrombopoiesis, which favors peripheral consumption of platelets as the likely mechanism of thrombocytopenia in these animals, over decreased platelet production.
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Kopperuncholan
authors.initials: K
authors.lastname: Namachivayam
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Krishnan
authors.initials: K
authors.lastname: MohanKumar
authors.affiliation: Faculty of Information and Communication Technology, University of Malta, Msida, Malta.
authors.forename: Lalit
authors.initials: L
authors.lastname: Garg
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Torres
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.|Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida.|Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, Florida.
authors.forename: Akhil
authors.initials: A
authors.lastname: Maheshwari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D007422:Intestines / Q000473:pathology; D063847:Mean Platelet Volume; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D011003:Ploidies; D013921:Thrombocytopenia / Q000097:blood* / Q000209:etiology / Q000473:pathology; D034061:Thrombopoiesis; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D015415:Biomarkers; D040201:Platelet Membrane Glycoprotein IIb; D014302:Trinitrobenzenesulfonic Acid