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Dr Ghada Al Harbi (RCSI-PhD-March 142022)Kathleen.pdf (3.9 MB)

Platelets Parameters in Sepsis and Septic Shock: Clinical Usefulness and Prognostic Value

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posted on 2022-07-22, 15:10 authored by Ghada Hamad AL-Harbi

Background: The primary role of platelets is in haemostasis, thrombosis, and wound healing. Nonetheless, there is mounting evidence that platelets play distinct roles in the inflammatory response and immunological control. This is due to platelet properties such as the capacity to bind pathogens, produce different immunoregulatory cytokines and chemokines, and express receptors for diverse immunological effects and regulatory activities. Furthermore, even though platelets lack a nucleus, they may manufacture a limited number of proteins and transport inflammatory chemicals to inflammatory cells by utilising messenger RNA (mRNA) as templates. For decades, researchers have investigated the relationship between platelets and inflammation. Platelet activation, adherence to endothelial cells, inflammatory chemical release promotes monocyte migration and adherence to the lesion, accelerating sepsis progression. Sepsis and septic shock are frequent reasons for admittance in intensive care Units (ICU). Sepsis is the leading cause of mortality worldwide. Early recognition and management are crucial for preventing progression to unfavourable outcomes. Distinguishing a biomarker that could unveil sepsis at an earlier stage is of supreme importance. The aim of this thesis is to investigate the platelet reactivity in sepsis/septic shock patients as determined by multiple platelet function assays. A prospective monocentric observational study using a Novel Sinnowa PL-12 haematology analyser was conducted. 321 Patients admitted to KHUH ICU between February 1st, 2019 and March 5th , 2020 were screened. Fifty-seven consecutive patients and 20 controls were enrolled in the study. Analysis of platelet count, maximum aggregation rate, mean platelet volume and mean platelet volume to platelet count ratio was performed. 

Results: Septic patients demonstrated lower ΔMPV results than controls following ADP, EPI, and COL stimulation. (ΔMPV) post Epinephrine stimulation predicts sepsis with a sensitivity of 88.9 % and a specificity of 61 %. Non-survivors showed significantly lower (ΔMPV) following Arachidonic acid, and COL stimulation. Together with standard blood biomarkers, such as CRP, neutrophils, or platelets count, ΔMPV may be a promising biomarker to diagnose sepsis, predict mortality and prognosis.

History

First Supervisor

Prof. Dermot Cox

Second Supervisor

Dr. Anis Chaari

Comments

Submitted for the Award of Doctor of Philosophy to the Royal College of Surgeons in Ireland, 2022

Published Citation

Al-Harbi GH,. Platelets Parameters in Sepsis and Septic Shock: Clinical Usefulness and Prognostic Value. [PhD thesis] Dublin: Royal College of Surgeons in Ireland; 2022

Degree Name

  • Doctor of Philosophy (PhD)

Date of award

2022-06-01

Programme

  • Doctor of Philosophy (PhD)

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