Abstract

BACKGROUND: Given that platelets support the integrity of the alveolar-capillary membrane, it is conceivable that thrombocytopenia may be associated with development of acute respiratory distress syndrome (ARDS). Yet, clinical studies confirming such an association are limited. We endeavoured to examine whether thrombocytopenia is independently associated with development of ARDS in critically ill patients. METHODS: First, we performed a systematic review and meta-analysis of observational studies reporting the number of patients at risk for ARDS with versus without thrombocytopenia who eventually developed ARDS. Next, we performed a secondary analysis using individual patient-level data from three large randomized controlled trials to estimate whether thrombocytopenia (defined as &lt; 100,000 platelets/µL) was independently associated with development of ARDS. RESULTS: In the meta-analysis, four observational studies (five cohorts) involving 3666 critically ill patients were included. Patients with versus without thrombocytopenia were more likely to develop ARDS [46.3% versus 33.2%; relative risk 1.41, 95% confidence intervals (CI) 1.23–1.63; <i>p</i> &lt; 0.001]. In the secondary analysis, data from 2927 critically ill patients were analyzed. After adjustment for confounders, including severity of illness, thrombocytopenia was not independently associated with development of ARDS (odds ratio 1.57, 95% CI 0.95–2.60; <i>p</i> = 0.080). The association between platelet count (as a continuous variable) and development of ARDS was non-linear and appeared U-shaped. CONCLUSIONS: Thrombocytopenia may not be independently associated with development of ARDS after adjustment for important confounders, such as severity of illness. Thrombocytopenia may serve as a marker of severe illness and its association with ARDS may not represent a mechanistic relationship. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-025-03444-x.