This study attempted to evaluate the effect of PLR before and after thrombolysis treatment on the outcomes in acute ischemic stroke patients. We found that PLR at 24 h after rtPA treatment, but not on admission, was an independent risk factor for poor outcome and death. In addition, we found PLR had no significant interaction with the risk of HT, no matter whether the index was calculated before or after thrombolysis.
Previous studies have shown that PLR has a strong relationship with ischemic events in general. For example, in a recent study, researchers suggested that PLR can be used in clinical practices for prediction of no reflow in patients with acute ST-segment elevation myocardial infarction after primary percutaneous intervention[8]. Simultaneously, the study by Tekesin A et al. [9] showed a significant association between PLR and cerebral vein thrombosis in suspected patients. Another study by Altintas O et al.[10] found that, in patients with acute ischemic stroke who underwent endovascular therapy, low-PLR values were shown to be correlated with better clinical outcome (mRS ≤ 2). In addition, in a retrospective study of 56 patients who had acute ischemic stroke diagnosed and underwent mechanical thrombectomy, researchers found that PLR had no relationship with clinical outcome, but PLR was lower in the group with a dramatic improvement in the 24th hour[11]. Compared with previous studies, the sample size of our study is relatively large and we further found that the patients with high-PLR values at 24 h after thrombolysis had poorer outcome (mRS > 2) and a higher occurrence of death compared with the patients with low-PLR values at the same time.
Platelets play an important role in prothrombotic status. A high platelet count may represent a higher tendency to thrombosis, leading to poor prognosis[16]. Moreover, platelets can release a variety of inflammatory factors and recruit leukocytes to the sites of inflammation and injury, which leads to the aggravation of inflammatory reaction in thrombus sites[17]. In a previous study, it was suggested that the increase of platelet count in patients with thrombus may be due to multiple inflammatory mediators that stimulate megakaryocyte proliferation and thus produce more platelets[18]. In contrast, lymphocytes are known to control inflammatory pathways[19, 20]. A decreased lymphocyte count may aggravate the injury of cerebral infarction and neurological deficits[21]. On the one hand, regulatory T cells, specific subtypes of lymphocytes, play a key role in eliminating inflammatory response, and act as the main brain protective immunomodulator in the process of acute stroke[22, 23]. On the other hand, a decrease in lymphocyte count may be an index to reflect the stress level of the body, which can reflect the production of cortisol-induced stress response and the activation of the renin–angiotensin system which further increases the production of pro-inflammatory cytokines promoting ischemic injury[21, 24, 25]. In general, lymphocytes have an important role in the healing and repairing inflammation[26].
PLR, as a combination of platelets and lymphocytes, has the advantage of reflecting not only the thrombus formation pathway, but also the inflammation pathway[27]. There are two main reasons why PLR may be superior to absolute platelet or lymphocyte count in predicting prognosis. First, PLR represents two inversely related predictors and immunologic pathways[20]. Second, previous studies have suggested that PLR is more stable compared with single platelet and lymphocyte counts, because platelet or lymphocyte counts could be altered by many physiologic and pathologic conditions[28–30]. Therefore, the PLR is more useful, rational and reliable for predicting the risk of poor outcome and death in patients. However, we did not find a significant association between PLR and HT in acute ischemic stroke patients after thrombolysis in this study. We think the association between PLR and HT needs further investigation in the future.
Also, the AUC for the PLR after 24 h appeared to be greater than that at baseline, and the mechanisms have not been well established. We suspect that there may be two reasons to explain this phenomenon. One reason is that, within 24 hours of stroke, the lymphocytes accumulate in cerebral vessels at a later time [31]. So we speculated that the PLR values after 24 h was more valuable than the PLR at baseline for reflecting the patients’ conditions. The other reason is that the recent study suggested that the lymphocyte count after ischemic stroke exhibited a significant temporal variation which was characterized by “dynamic” changes[22, 32]. Moreover, thrombolysis also has a significant impact on the PLR. Thus, the PLR values on admission may be unable to dynamically and comprehensively reflect the patients’ conditions.
Our study has some limitations. First, the study was retrospective and the data included patients only treated at one hospital, which might lead to selection bias. Second, we only examined PLR at two time points, which was before thrombolysis and 24 h after thrombolysis. The dynamic change of PLR during the whole process of ischemic injury and its definite mechanisms have not been fully elucidated. Further investigations are needed to explore the relevant mechanisms of this study. Lastly, some other inflammatory markers such as neutrophils, CRP, and IL-2 were not taken into consideration.
In conclusion, we found that the PLR at 24 h after rtPA thrombolysis, rather than before thrombolysis, was associated with the risk of poor outcome and death in acute ischemic stroke patients, which can be used as a simple, novel and inexpensive method for predicting patients’ prognosis.