PLATELET TRAITS AND SEPSIS RISK AND PROGNOSIS: A BIDIRECTIONAL TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE SHOCK Pub Date : 2025-04-01 Epub Date: 2024-08-12 DOI:10.1097/SHK.0000000000002447

Zhonghai Song, Hua Li, Jing Zhang, Yaomeng Huang, Shichao Gao

{"title":"PLATELET TRAITS AND SEPSIS RISK AND PROGNOSIS: A BIDIRECTIONAL TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.","authors":"Zhonghai Song, Hua Li, Jing Zhang, Yaomeng Huang, Shichao Gao","doi":"10.1097/SHK.0000000000002447","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Background: Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis. Methods: MR analysis was used to investigate the causal effect of four platelet traits-platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW)-on sepsis risk and prognosis. Additionally, the study explored the reverse causality, assessing the impact of sepsis on these platelet traits. Genetic variants from large-scale genome-wide association studies served as instrumental variables to infer causality. Sensitivity analyses and heterogeneity tests were conducted to ensure the validity and robustness of the results. Results: Genetically predicted decreased PCT (OR = 0.938, P = 0.044) and MPV (OR = 0.410, P = 0.006) were associated with an increased risk of sepsis. In the reverse direction, 28-day sepsis mortality was significantly associated with decreased PLT (OR = 0.986, P = 0.034). No significant causal relationships were observed between sepsis and other platelet traits. Conclusions: This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"520-526"},"PeriodicalIF":2.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002447","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/12 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Abstract: Background: Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis. Methods: MR analysis was used to investigate the causal effect of four platelet traits-platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW)-on sepsis risk and prognosis. Additionally, the study explored the reverse causality, assessing the impact of sepsis on these platelet traits. Genetic variants from large-scale genome-wide association studies served as instrumental variables to infer causality. Sensitivity analyses and heterogeneity tests were conducted to ensure the validity and robustness of the results. Results: Genetically predicted decreased PCT (OR = 0.938, P = 0.044) and MPV (OR = 0.410, P = 0.006) were associated with an increased risk of sepsis. In the reverse direction, 28-day sepsis mortality was significantly associated with decreased PLT (OR = 0.986, P = 0.034). No significant causal relationships were observed between sepsis and other platelet traits. Conclusions: This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

血小板特征与败血症风险和预后：一项双向双样本孟德尔随机研究。

背景：败血症是一种危重病症，其特点是宿主对感染的反应失调。脓毒症患者经常表现出血小板异常，但血小板在脓毒症中的因果作用仍不清楚。本研究采用双向双样本孟德尔随机化（MR）方法研究血小板与败血症之间的因果关系：方法：采用 MR 分析法研究血小板计数（PLT）、血小板标准（PCT）、血小板平均体积（MPV）和血小板分布宽度（PDW）这四种血小板特质对脓毒症风险和预后的因果效应。此外，该研究还探讨了反向因果关系，评估了败血症对这些血小板特征的影响。来自大规模全基因组关联研究（GWAS）的基因变异作为工具变量，用于推断因果关系。为了确保结果的有效性和稳健性，我们进行了敏感性分析和异质性检验：结果：基因预测的 PCT（OR = 0.938，p = 0.044）和 MPV（OR = 0.410，p = 0.006）降低与败血症风险增加有关。相反，28 天败血症死亡率与 PLT 下降显著相关（OR = 0.986，p = 0.034）。脓毒症与其他血小板特征之间没有发现明显的因果关系：本研究表明，低 PCT 和 MPV 水平与脓毒症风险增加之间存在因果关系。此外，预后不良的败血症与 PLT 的降低存在因果关系。这些发现为血小板特征与败血症之间的因果关系提供了新的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.