Trajectories of platelet indices and their association with mortality in the ICU-a longitudinal cohort study

While thrombocytopenia's link to mortality is known, the prognostic impact of longitudinal trajectories of platelet indices in combination with analysis of thrombocytopenia's mediating role remains unexplored. This is the first study that addresses this significant gap by investigating the association between seven platelet indices trajectory subphenotypes and ICU mortality, considering thrombocytopenia's mediating influence. Four hundred and twenty-one adult ICU patients were enrolled in this longitudinal cohort study. Three trajectories were identified for each platelet index, namely: descending, stable, and ascending, and using a regression, receiver-operating characteristic curve, and mediation analysis, their associations with 90-day mortality were evaluated with the mediating effect of thrombocytopenia. The findings were adjusted (prefixed 'a') for covariates. The heterogeneous trajectories significantly associated with 90-day mortality included: descending platelet count (PC) [aOR, 2.75 (CI, 1.56-4.85), p = 0.0005, aAUC, 0.783], descending plateletcrit (PCT) [aOR, 3.49 (CI, 1.88-6.46), p = 0.0001, aAUC, 0.802], ascending platelet distribution width (PDW) [aOR, 2.04 (CI, 1.13-3.71), p = 0.0188, aAUC, 0.776], and ascending percent-immature platelet fraction (%-IPF) [aOR, 2.25 (CI, 1.29-3.94), p = 0.0045, aAUC, 0.778], with 11.6% (p = 0.027), 12.0% (p = 0.019), 22.1% (p = 0.011), and 15.9% (p = 0.024) effects mediated by thrombocytopenia, respectively. In contrast, ascending mean platelet volume (MPV) was significantly and independently associated with mortality [aOR, 3.04 (CI, 1.45-6.39), p = 0.0033, aAUC, 0.781], without the effect mediated by thrombocytopenia (p = 0.056). The trajectories of platelet-large cell ratio (P-LCR) and absolute-immature platelet count (A-IPF) were not significantly associated with the risk of mortality (p > 0.05). This study demonstrated that descending PC and PCT and ascending PDW and %-IPF, mediated by thrombocytopenia, and ascending MPV, without mediation by thrombocytopenia, are useful longitudinal trajectories for predicting 90-day mortality in the ICU.