Subphenotypes of platelet count trajectories in sepsis from multi-center ICU data

Although thrombocytopenia on admission to the ICU is associated with increased in-hospital mortality in septic patients, the role of longitudinally measured platelet counts, which are dynamically changing, is unclear. We aimed to identify patterns of dynamic platelet count trajectories and evaluate their association with outcomes and thrombocytopenia in septic patients. We tested the longitudinal platelet trajectory patterns of sepsis patients within the first four days of ICU admission in the MIMIC-IV database and their association with 28-day mortality, and independently validated our findings in the eICU-CRD database. Statistical methods used included multivariate regression, propensity score analysis, doubly robust estimation, gradient boosting model, and inverse probability weighting to ensure the robustness of our findings. A total of 22,866 septic patients were included in our study. The trajectory analysis categorizes patients into ascending (AS), stable (ST), or descending (DS) patterns. The risk of 28-day mortality was increased in the DS patients (OR = 2.464, 95%CI 1.895-3.203, p < 0.001) and ST patients (OR = 1.302, 95%CI 1.067-1.589, p = 0.009) compared to AS patients. The AS patients had lower ICU length of stay (2.36 vs. 4.32, p < 0.001) and 28-day maximum SOFA scores (5.00 vs. 6.00, p < 0.001) than the DS patients, but had more ventilator-free days within 28 days than the DS group (26.00 vs. 24.00, p < 0.001). The mediating effect of thrombocytopenia was significant (p < 0.001 for the average causal mediation effect (ACME)). Longitudinal platelet trajectory was associated with risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through thrombocytopenia.