This study of 3265 patients shows that the independently combined effect of high WBC count and low platelet count on in-hospital mortality and pneumonia among AIS patients. Patients with high WBC count (≥ 8.3*109/L) and low platelet count (< 162 *109/L) tended to be associated with a 2.07-fold and 2.29-fold increase in the risk of in-hospital mortality and pneumonia respectively. Moreover, the lowest PWR participants was associated with greater risk of pneumonia. Furthermore, the predictive value of combined WBC and platelet count on in-hospital mortality and pneumonia appear to be better than WBC or platelet alone.
A growing body of studies have demonstrated that a high WBC count or low platelet count at baseline were significantly increased the risk of poor functional outcome and mortality after AIS3, 6–8. Data from the registry of the Canadian Stroke Network of 8829 AIS patients indicated higher WBC at baseline associated with greater risk of disability at hospital discharge as well as 30 days mortality3. Yang et al study of 101527 AIS patient with thrombolysis treatment found the baseline platelet < 150 *109/L was associated with higher in-hospital mortality and a higher incidence of intracranial hemorrhage6. For the significant interaction between platelets and WBC on regulation of both hemostatic and inflammatory processes9, two studies seen the combined effect of platelets and WBC for predict clinical outcome among AIS patients13, 14. A study of 168 AIS patients given thrombolysis treatment indicated patients with low PWR was associated with poor outcome at 90 days13. Cao et al study enrolled 633 AIS patients shown low PWR as well as other marker were increased the risk of 90 days mortality14. In present large multicenter study, we found the combined effect of high WBC count and low platelet count on in-hospital mortality. AIS patients with baseline WBC count ≥ 8.3*109/L and platelet count < 162 *109/L associated with a 2.07-fold risk of in-hospital mortality. We also found the predictive value of combined WBC count and platelet count for in-hospital mortality was better than WBC count or platelet count alone.
It is well known that increased WBC was the marker of inflammation and prior studies had shown the significant association between increased WBC and pneumonia after AIS5,17. The role of platelets in hemostasis is well established and more recently studies indicated platelets also play a key role of regulation inflammatory processes9. The interaction to leukocyte or monocyte and secreted mediators were the underlying mechanisms of platelets regulation inflammatory processes9, 18–21. Some studies have been indicated low platelet was increased the risk as well as the severity of pneumonia11,12. A study from china shown low platelet count is an independent risk factor of postoperative pneumonia in patients with type A acute aortic dissection (AAAD) 12. As for coronavirus disease 2019 (COVID-19), a meta-analysis of nine studies with 1779 COVID-19 patients indicated low platelet count was associated with increased risk of severe disease11. Additionally, a study from Canada found the low PWR was significantly increased the risk of pneumonia in patients undergoing radical nephrectomy for renal malignancy22. However, no studies investigate the prognostic of the combined of WBC count and platelet on pneumonia after AIS. In present study, we found patients with baseline WBC count ≥ 8.3*109/L and platelet count < 162 *109/L associated with a 2.29-fold risk of pneumonia. Moreover, we noted the predictive value of combined WBC count and platelet count for pneumonia was better than WBC count or platelet count alone.
In present study, we also do sensitivity analyses evaluate the relationship between PWR and in-hospital mortality and pneumonia. We noted patients with lowest PWR was significant associated with a high risk of pneumonia but not in-hospital mortality in comparison to highest group after adjust potential confounders. The positive association between low PWR and pneumonia support the combined effect of WBC count and platelet count on predict the risk of pneumonia. While the relationship between low PWR and high risk of in-hospital mortality was not significant after adjust potential confounders, which indicated combined WBC count and platelet count with cutoff value is better and feasibility in clinical practice. Early two studies13, 14 shown low PWR was associated with high risk of 90 days mortality and poor outcome, which different with our study. Different outcomes definition, different study sample size and different cofounders in the models may cause the difference findings.
The strengths of this study include having a large dataset of patients from multiple centers and being the first study to evaluate the combination effect of WBC count and platelet count on in-hospital mortality and pneumonia. However, this study has several limitations. First, a proportion of patients were excluded due to a lack of WBC and platelet count data, which may cause selection bias. Secondly, this cohort included some patients whose time from onset to admission exceeded 24 hours, therefore, the levels of WBC and platelet count at admission might not accurately reflect the levels at stroke onset. However, our sensitivity analysis showed that the significance of the association remained when we restricted to patients with time from onset to admission ≤ 24 hours. Thirdly, we were precluded investigating the possible mechanism between WBC count and platelet count and in-hospital mortality as we lacked information on exact cause of death. Also, we lack the data of previous anti-platelet drug use, which may affect the platelet function. Finally, the follow-up period of our study is relatively short, thus we were unable to evaluate the combined long-term effect of WBC count and platelet count on AIS outcomes.