Abstract
This thesis comprehensively analyses a spectrum of platelet indices, encompassing and extending beyond the traditional platelet count, within the ICU. Six original research studies, utilising a prospectively collected dataset of patient demographics, laboratory results, clinical data, and outcomes, investigate these indices across diverse analytical, clinical, and prognostic scenarios. These studies include rigorous analytical performance evaluations of key platelet indices, an assessment of platelet transfusion impact, and an investigation of their prognostic significance for mortality risk within the ICU.Chapters 2 and 3 comprise the evaluation of analytical performance essential for the foundation of this research. Chapter 2 evaluates the reproducibility and stability of two key platelet indices: percentage of immature platelet fraction (%-IPF) and absolute- immature platelet fraction (A-IPF). The stability investigation was conducted in two parts: a larger study assessing stability over 24 h and a subsequent study examining stability over 72 h to determine the time points at which these indices exceeded the pre- defined stability thresholds. Chapter 3 consists of two reference interval studies for platelet indices. The first study aimed to establish sex-specific reference intervals, while the second investigated the influence of age on these reference intervals.
Chapter 4 adds a clinical dimension and bridges the analytical and prognostic aspects of the research by exploring the dynamic changes in platelet indices following platelet transfusion. This investigation reveals that plateletcrit and A-IPF remain stable post- transfusion, challenging the assumption that transfusions invariably alter all platelet indices. This finding has important implications for patient monitoring and personalised transfusion strategies.
Chapter 5 examines the prognostic significance of platelet indices through two distinct studies: a cross-sectional analysis and a longitudinal cohort study. The former, focusing on platelet indices at the point of admission as the most opportune time for clinical decision-making. This study identified A-IPF > 6.4 × 10⁹/L as an independent predictor of in-ICU mortality, while MPV > 9.5 fL and %-IPF > 6.3% independently predicted 90-day mortality, suggesting their potential utility in future ICU scoring systems. The latter, focusing on clinically meaningful subphenotype trajectories of platelet indices (i.e. descending, stable, and ascending) revealed an association between 90-day mortality and descending platelet count/plateletcrit trajectories coupled with ascending MPV, platelet distribution width, and %-IPF trajectories. Thrombocytopenia partially mediated these associations, except for the MPV-mortality link, which remained independent. This suggests distinct mortality mechanisms and a complex interplay between platelet indices, thrombocytopenia, and 90-day mortality.
In conclusion, this thesis contributes to the understanding of platelet indices dynamics in critically ill patients. The collective findings from the evaluation of analytical performance evaluations, assessments of platelet transfusion impact, and investigations of prognostic significance advocate for integrating platelet indices into routine clinical assessments and prognostic models. These findings challenge traditional perspectives, offer new insights into the role of platelet indices in critical care, and pave the way for improved patient monitoring and personalised treatment, ultimately enhancing patient care and outcomes in the ICU.
| Date of Award | 9 Jul 2025 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Mridula Chopra (Supervisor) & Gavin Knight (Supervisor) |