Association of longitudinal platelet count trajectory with ICU mortality: A multi-cohort study

Jiajin Chen; Xi Gao; Sipeng Shen; Jingyuan Xu; Zhe Sun; Ruilang Lin; Zhixiang Dai; Li Su; David C Christiani; Feng Chen; Ruyang Zhang; Yongyue Wei

doi:10.3389/fimmu.2022.936662

Association of longitudinal platelet count trajectory with ICU mortality: A multi-cohort study

Front Immunol. 2022 Aug 19:13:936662. doi: 10.3389/fimmu.2022.936662. eCollection 2022.

Authors

Jiajin Chen¹, Xi Gao², Sipeng Shen¹, Jingyuan Xu³, Zhe Sun¹, Ruilang Lin¹, Zhixiang Dai¹, Li Su⁴, David C Christiani⁴, Feng Chen¹, Ruyang Zhang¹, Yongyue Wei¹

Affiliations

¹ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
² Department of Immunology, School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
³ Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
⁴ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Abstract

Objective: Platelet (PLT) engages in immune and inflammatory responses, all of which are related to the prognosis of critically ill patients. Although thrombocytopenia at ICU admission contributes to in-hospital mortality, PLT is repeatedly measured during ICU hospitalization and the role of longitudinal PLT trajectory remains unclear. We aimed to identify dynamic PLT trajectory patterns and evaluate their relationships with mortality risk and thrombocytopenia.

Methods: We adopted a three-phase, multi-cohort study strategy. Firstly, longitudinal PLT trajectory patterns within the first four ICU days and their associations with 28-day survival were tested in the eICU Collaborative Research Database (eICU-CRD) and independently validated in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Secondly, the relationships among PLT trajectory patterns, thrombocytopenia, and 28-day mortality were explored and validated. Finally, a Mortality GRade system for ICU dynamically monitoring patients (Mortality-GRID) was developed to quantify the mortality risk based on longitudinal PLT, which was further validated in the Molecular Epidemiology of Acute Respiratory Distress Syndrome (MEARDS) cohort.

Results: A total of 35,332 ICU patients were included from three cohorts. Trajectory analysis clustered patients into ascending (AS), stable (ST), or descending (DS) PLT patterns. DS patients with high baseline PLT decline quickly, resulting in poor prognosis. AS patients have low baseline PLT but recover quickly, favoring a better prognosis. ST patients maintain low PLT, having a moderate prognosis in between (HR _ST _vs _AS = 1.26, 95% CI: 1.14-1.38, P = 6.15 × 10^-6; HR _DS _vs _AS = 1.58, 95% CI: 1.40-1.79, P = 1.41 × 10^-13). The associations remained significant in patients without thrombocytopenia during the entire ICU hospitalization and were robust in sensitivity analyses and stratification analyses. Further, the trajectory pattern was a warning sign of thrombocytopenia, which mediated 27.2% of the effects of the PLT trajectory on 28-day mortality (HR _indirect = 1.11, 95% CI: 1.06-1.17, P = 9.80 × 10^-6). Mortality-GRID well predicts mortality risk, which is in high consistency with that directly estimated in MEARDS (r = 0.98, P = 1.30 × 10^-23).

Conclusion: Longitudinal PLT trajectory is a complementary predictor to baseline PLT for patient survival, even in patients without risk of thrombocytopenia. Mortality-GRID could identify patients at high mortality risk.

Keywords: critical care; immunity; inflammation; longitudinal trajectory; multi-cohort; platelet count; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Critical Illness
Humans
Intensive Care Units
Platelet Count
Respiratory Distress Syndrome*
Thrombocytopenia*