In this retrospective cohort research, GBTM was applied to demonstrate PC trajectories in patients with sepsis and PC trajectories were related to hospital mortality. In addition, we observed that PC trajectories were also related to infection control rate, time to infection control and RBC transfusion during first week of ICU admission.
It is well known that the progression of sepsis is rapid, so the starting point of sepsis is difficult to determine accurately. In our study design, the starting point of sepsis was relatively unified (within 2 days of ICU admission) in the expectation of obtaining an accurate trend in platelet count changes before and after the start of sepsis, although the study was retrospective. It can be seen that there is a clear differentiation of platelet count (< 150, > 200, >400) at the beginning of sepsis or before sepsis in the 3 groups of patients, which may represent different pathological states and consequently different trajectories of development. Akca et al. observed an early sharp drop followed by an improvement in platelet count, which was consistent with our study. But we did not find a continuous low level PC trajectory (< 50\(\times\) 109/L), which may be because the proportion of this kind of patients is too low to form a trajectory, or because there will be a new change point in PC after 7 days. It is as expected that low PC trajectory is associated with hospital mortality rather than 90-days mortality. Surprisingly, low PC trajectory is associated with a higher infection control rate and less time to infection control, which may because platelets can induce an acute period response to infection(18, 19), and platelet–leukocyte interactions play the crucial role in defending against infections during inflammation and sepsis(20). The association of red blood cell transfusion with low PC trajectory can be explained by the fact that clinical decisions tend to red blood cell transfusion in septic patients with lower platelet counts under high pressure such as invasive procedures, surgery, etc. The mean difference in maximum SOFA score between three groups was consistent with trends in platelet variation, implying that there were no significant differences between the three groups in terms of systemic function other than blood system, although we did not perform further analysis of the individual system scores. We did not found the association of AKI incidence with PC trajectories,w, ich means platelet function played a more important role in AKI rather than quantity. Increased platelet activation marker levels in clinical and experimental models of AKI include P-selectin, TxB2, CCL5, PF4(21). Unfortunately, the limitations of the retrospective study prevented us from obtaining these data.
In the analysis of risk factors, the septic patients with Vasopressor use (1st 24h) and RRT use (1st 24h) are associated with low PC, which reflects deterioration in respiratory and renal function and so does the platelet function. Although we identified the respective effects of some antibiotics on platelet trajectories, this may be of little help in clinical work, as antibiotic use is often combined. Interestingly, we found that septic patients without diabetes and without hypertension had a higher risk of forming low PC trajectories. Jin-Young Hwang et al, reported that the incidence of type 2 DM increased as the serum platelet count at baseline increased within the normal range(22). In addition, platelet volumes and counts are inversely correlated, and the total platelet mass (platelet count\(\times\) MPV) remains stable(23, 24). In a meta-analysis, higher MPV and PDW in T2DM, but not a parallel reduction in platelet count means that the physiological negative feedback between counts and volume is dysregulated in T2DM, resulting in a higher platelet mass(25). Men have a high risk at low PC trajectory, which may because women generally have higher PC(26, 27).CCU/CVICU patients tend to use antiplatelet drugs which may result in low PC. The correlation between platelet transfusion and the use of heparin and trajectory may be inverted, in the sense that differences in trajectory drive changes in clinical decision making.
Our research is the first to examine the effects of PC trajectories on clinical outcomes in patients with sepsis. But our research still had some limitations. Firstly, the observation-based research cannot provide an explanation for the causality between PC trajectories and outcomes. Secondly, we probably did not correct for further possible confounding factors. Thirdly, we didn't think about platelet function in sepsis, Consequently, we are unable to presume a pathophysiologic mechanism for higher mortality in septic patients with low PC. Fourth, the correct understanding of GBTM is that the model is data driven and it tends to present data characteristics. Specifically for this study, we found 3 PC trajectories, but reality is often complex and there may still be these other PC change trends that were not found due to the limitations of this study.