Thromb Haemost 2019; 119(03): 431-438
DOI: 10.1055/s-0038-1676794
Blood Cells, Inflammation and Infection
Georg Thieme Verlag KG Stuttgart · New York

Platelet Glycoprotein VI Haplotypes and the Presentation of Paediatric Sepsis

Ahmed Asfari
1  Section of Cardiac Critical Care Medicine, Department of Pediatric Cardiology, University of Alabama at Birmingham College of Medicine, Birmingham, Alabama, United States
2  Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Judith A. Dent
3  Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Adam Corken
3  Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Danielle Herington
4  Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
5  Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States
,
Vamsikrishna Kaliki
6  Pediatric Emergency Medicine, University of Oklahoma, Oklahoma City, Oklahoma, United States
,
Natasha Sra
3  Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Glenda Hefley
2  Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Sanjiv Pasala
2  Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Parthak Prodhan
2  Section of Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Jerry Ware
3  Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
› Author Affiliations
Funding Financial support by NIH R21AR061991 (to J.W.) and Arkansas Children's Hospital Research Institute and the Children's University Medical Group (to A.A.) is acknowledged.
Further Information

Publication History

18 July 2018

23 November 2018

Publication Date:
31 December 2018 (eFirst)

Abstract

Sepsis triggers a complex series of pathophysiologic events involving inflammatory responses and coagulation abnormalities. While circulating blood platelets are well-characterized for their contributions to coagulation, increasingly platelet-dependent effects on inflammation are being recognized. Here, we focus on the platelet membrane receptor, glycoprotein VI (GPVI), and its role in platelet microparticle (pMP) release. The GPVI receptor is a platelet-specific collagen membrane receptor that, upon ligand binding, facilitates the release of pMPs. As membrane-bound platelet fragments of less than 1 μm, pMPs are known to have both pro-inflammatory and pro-coagulant properties. Thus, pMPs are potentially impacting sepsis at multiple stages of the inflammatory response. Studies are presented documenting the impact of the most common GPVI haplotypes, GPVIa and GPVIb, on pMP levels and release in healthy individuals (n = 49). The GPVIa haplotype corresponds to an approximately twofold increase in circulating pMPs as a percentage of total microparticles in healthy individuals along with a heightened in vitro release of pMPs. Additionally, patients admitted to a paediatric intensive care unit (ICU) (n = 73) with an initial diagnosis of sepsis were recruited and their GPVI haplotypes determined. Septic patients of the GPVIa haplotype (n = 59) were statistically more likely to present with a diagnosis of severe sepsis or septic shock, as compared with GPVIb individuals (n = 14). Independent disease classification via PELOD-2 and Pediatric Risk of Mortality III scores confirmed individuals with the GPVIa haplotype were more likely to have significant organ failure. Thus, GPVI haplotypes influence pMP levels in the circulation and are predictive of sepsis severity when presenting to the ICU.

Supplementary Material