Prognostic significance of platelet-to-lymphocyte and platelet-to-neutrophil ratios in patients with mechanical thrombectomy for acute ischemic stroke

Article information

J Cerebrovasc Endovasc Neurosurg. 2022;24(3):221-231
Publication date (electronic) : 2022 April 21
doi : https://doi.org/10.7461/jcen.2022.E2021.10.003
1Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
2Department of Neurosurgery, St. Vincent’s Hospital, the Catholic University of Korea, Seoul, Korea
Correspondence to Ho Jun Yi Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Bucheon, Gyeonggi-Do,14584, Korea Tel +82-32-621-5289 Fax +82-32-621-5107 E-mail 431anarchy@naver.com
Received 2021 October 26; Revised 2021 December 23; Accepted 2021 December 23.

Abstract

Objective

The present study aimed to analyze the correlation between platelet-to-lymphocyte ratio (PLR) and platelet-to-neutrophil ratio (PNR) with prognosis of patients who underwent mechanical thrombectomy (MT).

Methods

A total of 432 patients was included, PLR and PNR were calculated from laboratory data on admission. Prognosis was evaluated with a modified Rankin Scale at 3 months after MT. Using receiver operating characteristic (ROC) analysis, optimal cutoff values of PLR and PNR were identified to predict the prognosis after MT. Multivariate analyses were performed to identify the relationship of PLR and PLR with prognosis of MT.

Results

Patients with favorable outcomes had a lower mean PLR (135.0, standard deviation [SD] 120.3) with a higher mean PNR (47.1 [SD] 24.6) compared with patients with unfavorable outcomes (167.6 [SD] 139.3 and 35.4 [SD] 22.4) (p<0.001 and <0.001, respectively). In ROC analyses, the optimal cutoff value of PLR and PNR to predict the 3 months prognosis were 145 and 41, respectively (p=<0.001 and p=0.006). In multivariate analysis, PLR less than 145 (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.06–2.06; p=0.016) and PNR greater than 41 (OR 1.22, 95% CI 1.10–1.62; p=0.022) were predictors of favorable outcome at 3 months.

Conclusions

In patients with MT, PLR and PNR on admission could be predictive factors of prognosis and mortality at 3 months. Decreased PLR and increased PNR were associated with favorable clinical outcome 3 months after MT.

INTRODUCTION

Stroke is a major cause of mortality and morbidity, and ischemic stroke accounts for about 80% of all stroke [12,32]. Among the types of stroke, acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) can cause severe disabilities and life threatening conditions [9]. The current potent treatment paradigm for LVO is mechanical thrombectomy (MT), and its recanalization rate is greater than 90% [10]. However, the independent functional outcomes of patients after MT is in the 50% range, and is influenced by various factors [26,35,38]. Recently, many studies have analyzed the factors affecting clinical prognosis of MT, and the inflammatory response plays a pivotal role in progression of brain damage caused by AIS [7,22,30].

Thromboembolism, as main cause of LVO, has been considered as a complicated interaction of the inflammatory response [34]. Platelets are involved in the process of thrombosis, which plays a crucial role in initiation and development of the atherosclerotic process with plaque rupture [16,21,37]. In addition, white blood cells (WBC) contributed to the pathophysiology of ischemic changes in the brain, and activated leukocytes are released in damaged brain tissues with pro-inflammatory chemokines [14,18]. Among the leukocytes, neutrophils enhance the release of inflammatory mediators; in contrast, lymphocytes contribute to healing and repair mechanisms of inflammation [5,15,30].

Various studies have been conducted to determine the ratios of platelets with WBC subtypes, as diagnostic or prognostic predictive factors. The platelet-to-lymphocyte ratio (PLR) has been used as a systemic inflammatory biomarker to predict the prognosis of neoplasms, coronary disease, autoimmune disease and stroke [23,24,33,36]. Furthermore, the platelet-to-neutrophil ratio (PNR) and platelet-to-WBC ratio (PWR) have been introduced as prognostic markers in patients with AIS [4,20]. However, only a limited number of papers has evaluated these ratios to predict the prognosis for patients who underwent MT for LVO. Thus, we evaluated the PLR, PNR, and PWR of peripheral blood in patients who underwent MT. We also aimed to investigate the potential predictive value of these ratios on clinical outcome after MT. The associations of PLR, PNR, and PWR with functional outcomes and prognosis of patients with MT were analyzed.

MATERIALS AND METHODS

Study population

In our retrospective study, prospectively collected data from each institution’s stroke data base were reviewed, after obtaining approval of the local Institutional Review Board. From January 2014 to February 2020, a total of 432 patients who underwent MT by LVO was identified. The inclusion criteria was AIS patients who underwent MT for LVO at each institution. Exclusion criteria were as follows: (1) patients with missing laboratory data, or loss to follow up within 3 months; (2) history of infection or surgery within 4 weeks prior to AIS onset; (3) history of autoimmune disease (e.g. rheumatic autoimmune disease, lupus), or malignancy; and (4) known underlying hematologic disorders and severe kidney or liver dysfunction. Pretreatment infection was defined as pneumonia, urinary tract infections, or fever or other typical clinical manifestations, during the pre-interventional period. Before the MT, intravenous thrombolysis (IVT) with a tissue plasminogen activator (alteplase) was applied within 4.5 hours after stroke onset at a maximum dose of 0.9 mg/kg in accordance with the European Cooperative Acute Stroke Study (ECASS) III trial [13]. All of MT procedures were performed with a stent retriever or a combined technique [6]. LVO included occlusion of the intracranial carotid artery, middle cerebral artery, anterior cerebral artery, or posterior circulation (vertebral artery, or basilar artery), as established with computed tomography angiography.

Clinical data and laboratory measurements

Clinical characteristics of the patients included demographic findings; age, gender, risk factors, stroke etiology by TOAST criteria [2], target occlusion site, laboratory findings on admission, IVT, alberta stroke program early CT score (ASPECTS), national institutes of health stroke scale (NIHSS) (range, 0-42, with higher score indicating more severe neurologic deficit), and time from symptom onset to groin puncture. Risk factors constituted history of hypertension, diabetic mellitus, atrial fibrillation, coronary artery disease, prior stroke or transient ischemic attack (TIA), smoking, dyslipidemia, and body mass index (BMI). Laboratory findings contained red blood cells, WBC differentials, hemoglobin, hematocrit, platelets, prothrombin time, activated partial thromboplastin time, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), total protein, blood urea nitrogen (BUN), creatinine (Cr), BUN/Cr ratio, glycated hemoglobin (HbA1c), serum glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). All laboratory findings were evaluated using the peripheral venous blood samples collected on admission to the emergency department. PLR, PNR, and PWR were calculated by dividing the platelet count by the lymphocyte count, the platelet count by the neutrophil count, and the platelet count by WBC count, respectively [4,20].

Procedure details and clinical outcomes

Procedure time was determined as time from groin puncture to reperfusion. Based on the final angiogram, a successful recanalization was defined, according to the modified treatment in the cerebral infarction (m-TICI) scale of 2b or 3 [39], and the first-pass reperfusion indicated an m-TICI of 2b or 3 reperfusion with the first pass of the stent retriever [28]. Clinical outcomes comprised the modified Rankin Scale (mRS) score at 3 months (a favorable functional outcome means 3 months mRS score of 0 to 2), symptomatic intracerebral hemorrhage (sICH), hemorrhagic transformation (HT) of infarct, and mortality at 3 months. sICH was defined as any hemorrhage on a computed tomography taken after the procedure with an increase of ≥4 points on the initial NIHSS score. HT of infarct was confirmed by susceptibility weighted imaging at 7 days after MT.

Statistical analysis

All data were processed using Stata Statistical Software, release 15 (Stata, College Station, TX, USA). All of the patients were dichotomized according to the mRS at 3 months (favorable 0-2 vs unfavorable 3-6). Categorical variables were analyzed with χ2 test or Fisher’s exact test, and Student’s t-test or Mann-Whitney U test was used to compare continuous variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values of PLR, PNR, and PWR to predict the prognosis of patients with MT. Univariate and multivariate logistic regression analyses were used to verify factors that correlated with clinical outcomes, and to compute odds ratio (OR) with 95% confidence interval (CI) estimates for each endpoint. The variables with p<0.20 in univariate analysis were entered into a backward multivariate logistic regression analysis, and a two-tailed p-value ≤0.05 was considered to indicate a significant difference.

RESULTS

Baseline characteristics and outcomes

A total of 432 patients, 240 showed favorable outcomes at 3 months (mRS score 0-2, 56.7% were male), and unfavorable outcomes at 3 months (mRS score 3-6, 50.5% were male) were found in the other 192 patients. Patients with unfavorable outcomes (mean 73.4 yrs [SD] 11.8) were older than those with favorable outcomes (mean 66.0 yrs [SD] 13.5) (p=<0.001). There were no significant differences in risk factors, stroke etiology, and distribution of occlusion site between the groups. Compared with the unfavorable outcome group, the favorable outcome group showed lower mean levels of neutrophils and hsCRP, but higher mean lymphocyte level (p=0.032, 0.010, and 0.030, respectively). A lower mean value of PLR (135.0 [SD] 120.3) with higher mean value of PNR (47.1 [SD] 24.6) and PWR (27.7 [SD] 12.1) were found in favorable outcome patients, compared with those of unfavorable outcome patients (167.6 [SD] 139.3, 35.4 [SD] 22.4, and 22.4 [SD] 10.8, respectively) (p=<0.001, <0.001, and 0.009) (Fig. 1). In addition, the favorable outcome patients had a higher median ASPECT (9 [inter interquartile range, IQR] 8-10), lower mean initial NIHSS (8.1 [SD] 5.1), and shorter mean symptom to puncture time (212 [SD] 98) than patients with unfavorable outcomes (8 [IQR] 6-10, 13.9 [SD] 6.6, and 298 [SD] 133, respectively) (p=0.014, <0.001, and <0.001). The differences in other baseline characteristics and laboratory findings between the groups not statistically significant. Patients with favorable outcomes had shorter procedure times with greater achievement of successful recanalization and first pass reperfusion, than patients with unfavorable outcomes (p=0.002, <0.001, and 0.015, respectively). In terms of clinical outcomes, lower occurrence of sICH and HT of infarct was found in the favorable outcome group, compared with the unfavorable outcome group (p=<0.001 and <0.001, respectively) (Table 1).

Fig. 1.

Box plots of platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR) between the groups. (A) The patients with favorable modified Rankin Scale (mRS) score (0-2) had lower mean PLR value than patients with unfavorable mRS (p<0.001). (B) Comparison of PNR between groups showed significantly higher PNR in patients with favorable mRS (p<0.001). (C) The mean value of PWR was higher in favorable mRS patients, compared with unfavorable mRS patients (p=0.009).

Baseline characteristics and outcomes of patients, according to functional outcomes at 3 month

Association of PLR, PNR, and PWR with 3 months clinical outcomes

According to ROC analysis, the optimal cutoff value of PLR level was 145 to predict the 3 months prognosis (area under the curve [AUC] 0.663, 95% CI 0.611–0.715; p<0.001). In addition, the optimal cutoff values of PNR and PWR to differentiate between favorable (mRS 0-2) and unfavorable (mRS 3-6) outcomes at 3 months were identified as 41 and 25, respectively (AUC 0.616, 95% CI 0.572–0.660; p=0.001, and AUC 0.583, 95% CI 0.521–0.645; p=0.006) (Fig. 2).

Fig. 2.

Receiver operating characteristic (ROC) curve of platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR) on prognosis of patients who underwent MT for LAO. The optimal cutoff value of PLR level to discriminate between favorable (0-2) and unfavorable (3-6) modified Rankin Scale (mRS) scores at 3 months was 145 (area under the curve (AUC) 0.663, 95% CI 0.611–0.715; p<0.001). In addition, a PNR value of 41 (AUC 0.616, 95% CI 0.572-0.660; p=0.001) and PWR value of 25 (AUC 0.583, 95% CI 0.521-0.645; p=0.006) were identified as the optimal cutoff values to predict favorable 3 months mRS after MT, respectively. MT, mechanical thrombectomy; CI, confidence interval

Predictors of favorable clinical outcome after MT

Binary univariate and multivariate logistic regression analyses were performed to verify the predicting factors that were independently associated with favorable outcomes and mortality at 3 months. Younger age (<70 yrs) (OR 1.39, 95% CI 1.04–1.63; p=0.022), higher ASPECT (>8) (OR 2.24, 95% CI 1.64–4.08; p=0.012), lower NIHSS at admission (<8) (OR 3.64, 95% CI 2.21–6.01; p=0.002), achievement of successful recanalization (OR 2.27, 95% CI 1.17–4.43; p=0.036), lower occurrence of sICH (OR 0.14, 95% CI 0.04–0.52; p=0.003), decreased PLR value (<145) (OR 1.29, 95% CI 1.06–2.06; p=0.016), and increased PNR value (>41) (OR 1.22, 95% CI 1.10–1.62; p=0.022) were independently associated with favorable outcome at 3 months after MT (Table 2). In addition, greater occurrence of sICH was associated with increased of 3 month mortality (OR 2.23, 95% CI 1.02–4.96; p=0.040); in contrast, younger age (<70 yrs) (OR 0.31, 95% CI 0.12–0.76; p=0.010), lower NIHSS at admission (<70 yrs) (OR 0.37, 95% CI 0.16–0.86; p=0.021), decreased PNR value (<145) (OR 0.83, 95% CI 0.76–0.92; p=0.018), and increased PNR value (>41) (OR 0.94, 95% CI 0.82–0.96; p=0.042) could be predictive factors for a decrease in 3 month mortality (Table 3).

Predictors of favorable clinical outcome in univariate and multivariate logistic regression analyses

Predictors of 3 month mortality in univariate and multivariate logistic regression analyses

DISCUSSION

In this observational study, lower PLR value with higher PNR and PWR values was identified in patients with favorable prognoses, compared to patients with unfavorable prognoses. The optimal cutoff values of PLR, PNR, and PWR to predict the prognosis of MT were 145, 41, and 25, respectively. Our results revealed that PLR and PNR on admission could be independent predictive factors of prognosis in patients who underwent MT for LVO. Furthermore, there were significant correlations of prognosis after MT with the degree of PLR and PNR.

Atherosclerosis and thrombosis are primarily involved in the pathogenesis of LVO with AIS, and platelets and WBC subtypes are crucial in these processes [8]. Platelets participate in inflammation and thrombosis by releasing of pro-inflammatory chemokines, and its activation plays an important role in thrombus formation in response to atherosclerotic plaque rupture or endothelial cell erosion [19,25]. Excessive activation and aggregation of platelets may lead to thrombosis with vascular occlusion, and result in cardiovascular and cerebrovascular events [24]. Leukocytes also play a significant role in the vascular inflammatory response and brain damage after AIS [18]. In ischemic brain tissue, neutrophils exaggerate edema and promote the death of neurons by releasing inflammatory mediators and toxic-effective substances [31]. In previous studies, leukocytosis and neutrophilia have been reported to be associated with increased infarct volume and recurrence of stroke [3,11]. On the other hand, lymphocytes are inversely associated with inflammation, and a lower lymphocyte count represents an increased risk of stroke and mortality [1,24].

The PLR is a novel biomarker of systemic inflammation, and a number of studies has investigated the association of PLR with prognosis of patients with cerebrovascular diseases. Altintas et al. performed a comparative study to assess the relationship of PLR with clinical outcome and final infarct core volume in patients with endovascular therapy for AIS.1) The patients were divided into two groups based on a PLR level cut-off value of 145, and m-TICI 3 recanalization was more frequent in the low PLR group. Patients with low PLR had more favorable functional outcomes (mRS 0-2) compared to patients with high PLR. Jin et al. showed the prognostic significance of PLR for 3 months prognosis after AIS [20]. Idil Soylu et al. reported that the rate of carotid artery stenosis was higher in patients with a high PLR value (>163), and PLR was an independent predictor of stroke [17]. Deser et al. revealed that PLR is a predictor of stroke following carotid endarterectomy, with a threshold level of 145.30 [5]. These findings were similar to our study in patients who underwent MT, where the optimal cutoff value of PLR to predict a favorable outcome was 145. In addition, PLR less than 145 is an independent predictor of favorable mRS (0-2) and mortality at 3 months, and the proportion of patients with favorable outcome decreased as PLR increased.

There is currently limited amount of research for PNR in patients with stroke. Jin et al. investigated PNR in patients with AIS [20]. The PNR level on admission in the good prognosis group (53.7) was significantly higher than that of the poor prognosis group (44.3), and PLR level was associated with 3 months prognosis after AIS [20]. In our study, patients with favorable outcome (47.1) had higher PNR than those with unfavorable outcome (35.4). Furthermore, PNR (greater than 41) is an independent predictor of favorable outcome and decrease of mortality at 3 months. In terms of PWR, Chen et al. investigated its association with prognosis in AIS patients with IVT and determined that PWR (>23.52) was a predictor of good 3 month outcome [4]. Jin et al. also showed that PWR was correlated with 3 months outcome in patients with AIS, but the accuracy of PWR was lower than that of PNR for predicting prognosis [20]. The results of these studies are different from ours. In our study, the PWR value of patients with favorable outcome (27.7) was higher than for patients with unfavorable outcome (22.4), and 25 was the optimal cut-off value for predicting favorable outcome. However, based on our multivariate analysis, PWR is not an independent predictor of clinical outcome or mortality.

Leukocyte platelet aggregates have been considered as a novel marker of activated platelets, and prior studied have shown that leukocytes can be recruited via platelet secretory components with multiple chemokines and membrane ligands [4,8,18,27]. Similarly, our study revealed that platelet to WBC subtypes ratios reflect the inflammatory response and are associated with prognosis of MT. In addition to the PLR, PNR, and PWR, we previously conducted an analysis of other inflammation-based scores, including neutrophil to lymphocyte ratios and monocyte to high-density lipoprotein cholesterol ratio which are known to reflect the inflammation status after MT [29]. The exact mechanism of various hematological factors that reflect the inflammation status have not been clarified, but they are helpful in predicting the prognosis of patients with MT, and further research is needed.

There were some limitations to our study. First, this was a retrospective study with a relatively small sample size, which may induce selection bias and allow for errors in data interpretation. Second, unmeasured laboratory findings, such as platelet distribution width and mean platelet volume, could have contributed to the results of our study, although we adjusted our analyses for possible confounding variables. Third, we only measured laboratory data once on admission and did not evaluate dynamic changes with repeated measurements of laboratory findings at different time points. Fourth, other various disease or past history of drug use that we did not include in this study could affect the inflammatory reaction and results of our analyses. However, every effort was made to adjust for the possibility of confounding factors when we analyzed the data and interpreted the results.

CONCLUSIONS

Our study shows the clinical importance of PLR and PNR in MT for LVO. PLR and PNR on admission could be predictive factors of prognosis and mortality at 3 months in patients with MT. Furthermore, decreasing PLR and increasing PNR are independent factors for predicting favorable prognoses of patients who underwent MT. Further investigation is required to verify the results of our study and identify the mechanisms behind these findings.

Notes

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Acknowledgements

This work was supported by the Soonchunhyang University Research Fund.

References

1. Altintas O, Altintas MO, Tasal A, Kucukdagli OT, Asil T. The relationship of platelet-to-lymphocyte ratio with clinical outcome and final infarct core in acute ischemic stroke patients who have undergone endovascular therapy. Neurol Res 2016;Sep. 38(9):759–65.
2. Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. Classification of stroke subtypes. Cerebrovasc Dis 2009;27(5):493–501.
3. Buck BH, Liebeskind DS, Saver JL, Bang OY, Yun SW, Starkman S, et al. Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke 2008;Feb. 39(2):355–60.
4. Chen Z, Huang Y, Li S, Lin J, Liu W, Ding Z, et al. Platelet-to-white blood cell ratio: a prognostic predictor for 90-day outcomes in ischemic stroke patients with intravenous thrombolysis. J Stroke Cerebrovasc Dis 2016;Oct. 25(10):2430–8.
5. Deser SB, Yucel SM, Demirag MK, Guclu MM, Kolbakir F, Keceligil HT. The association between platelet/lymphocyte ratio, neutrophil/lymphocyte ratio, and carotid artery stenosis and stroke following carotid endarterectomy. Vascular 2019;Dec. 27(6):604–11.
6. Deshaies EM. Tri-axial system using the Solitaire-FR and Penumbra Aspiration Microcatheter for acute mechanical thrombectomy. J Clin Neurosci 2013;Sep. 20(9):1303–5.
7. Duan Z, Wang H, Wang Z, Hao Y, Zi W, Yang D, et al. Neutrophil-lymphocyte ratio predicts functional and safety outcomes after endovascular treatment for acute ischemic stroke. Cerebrovasc Dis 2018;45(5-6):221–7.
8. Franks ZG, Campbell RA, Weyrich AS, Rondina MT. Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke. Ann N Y Acad Sci 2010;Oct. 1207:11–7.
9. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med 2017;Sep. 5(9):691–706.
10. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;Apr. 387(10029):1723–31.
11. Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004;May. 35(5):1147–52.
12. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;Mar. 363(9411):768–74.
13. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;Sep. 359(13):1317–29.
14. Herz J, Sabellek P, Lane TE, Gunzer M, Hermann DM, Doeppner TR. Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice. Stroke 2015;Oct. 46(10):2916–25.
15. Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005;May. 45(10):1638–43.
16. Huo Y, Ley KF. Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 2004;Jan. 14(1):18–22.
17. Idil Soylu A, Arikan Cortcu S, Uzunkaya F, Atalay YO, Bekci T, Gungor L, et al. The correlation of the platelet-to-lymphocyte ratio with the severity of stenosis and stroke in patients with carotid arterial disease. Vascular 2017;Jun. 25(3):299–306.
18. Ishikawa T, Shimizu M, Kohara S, Takizawa S, Kitagawa Y, Takagi S. Appearance of WBC-platelet complex in acute ischemic stroke, predominantly in atherothrombotic infarction. J Atheroscler Thromb 2012;19(5):494–501.
19. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 2009;Aug. 102(2):248–57.
20. Jin P, Li X, Chen J, Zhang Z, Hu W, Chen L, et al. Platelet-to-neutrophil ratio is a prognostic marker for 90-days outcome in acute ischemic stroke. J Clin Neurosci 2019;May. 63:110–5.
21. Kaplan ZS, Jackson SP. The role of platelets in atherothrombosis. Hematology Am Soc Hematol Educ Program 2011;2011:51–61.
22. Kim JY, Park J, Chang JY, Kim SH, Lee JE. Inflammation after ischemic stroke: the role of leukocytes and glial cells. Exp Neurobiol 2016;Oct. 25(5):241–51.
23. Krenn-Pilko S, Langsenlehner U, Thurner EM, Stojakovic T, Pichler M, Gerger A, et al. The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients. Br J Cancer 2014;May. 110(10):2524–30.
24. Kurtul A, Ornek E. Platelet to lymphocyte ratio in cardiovascular diseases: a systematic review. Angiology 2019;Oct. 70(9):802–18.
25. Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008;Mar. 99(3):480–6.
26. Lopez HV, Vivas MF, Ruiz RN, Martinez JR, Navaridas BG, Villa MG, et al. Association between post-procedural hyperoxia and poor functional outcome after mechanical thrombectomy for ischemic stroke: an observational study. Ann Intensive Care 2019;May. 9(1):59.
27. Marquardt L, Anders C, Buggle F, Palm F, Hellstern P, Grau AJ. Leukocyte-platelet aggregates in acute and subacute ischemic stroke. Cerebrovasc Dis 2009;28(3):276–82.
28. Maus V, Brehm A, Tsogkas I, Henkel S, Psychogios MN. Stent retriever placement in embolectomy: the choice of the post-bifurcational trunk influences the first-pass reperfusion result in M1 occlusions. J Neurointerv Surg 2019;Mar. 11(3):237–40.
29. Oh SW, Yi HJ, Lee DH, Sung JH. Prognostic significance of various inflammation based scores in patients with mechanical thrombectomy for acute ischemic stroke. World Neurosurg 2020;Sep. 141:e710–717.
30. Otxoa-de-Amezaga A, Gallizioli M, Pedragosa J, Justicia C, Miro-Mur F, Salas-Perdomo A, et al. Location of neutrophils in different compartments of the damaged mouse brain after severe ischemia/reperfusion. Stroke 2019;Jun. 50(6):1548–57.
31. Perez-de-Puig I, Miro-Mur F, Ferrer-Ferrer M, Gelpi E, Pedragosa J, Justicia C, et al. Neutrophil recruitment to the brain in mouse and human ischemic stroke. Acta Neuropathol 2015;Feb. 129(2):239–57.
32. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;Dec. 50(12):e344–418.
33. Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol 2016;26(3):372–6.
34. Ringer AJ, Guterman LR, Hopkins LN. Site-specific thromboembolism: a novel animal model for stroke. AJNR Am J Neuroradiol 2004;Feb. 25(2):329–32.
35. Rudilosso S, Laredo C, Amaro S, Renu A, Llull L, Obach V, et al. Clinical improvement within 24 hours from mechanical thrombectomy as a predictor of long-term functional outcome in a multicenter population-based cohort of patients with ischemic stroke. J Neurointerv Surg 2021;Feb. 13(2):119–23.
36. Tao C, Wang J, Hu X, Ma J, Li H, You C. Clinical value of neutrophil to lymphocyte and platelet to lymphocyte ratio after aneurysmal subarachnoid hemorrhage. Neurocrit Care 2017;Jun. 26(3):393–401.
37. Walsh TG, Metharom P, Berndt MC. The functional role of platelets in the regulation of angiogenesis. Platelets 2015;26(3):199–211.
38. Wirtz MM, Hendrix P, Goren O, Beckett LA, Dicristina HR, Schirmer CM, et al. Predictor of 90-day functional outcome after mechanical thrombectomy for large vessel occlusion stroke: NIHSS score of 10 or less at 24 hours. J Neurosurg 2019;Dec. :1–7.
39. Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;Sep. 44(9):2650–63.

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Fig. 1.

Box plots of platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR) between the groups. (A) The patients with favorable modified Rankin Scale (mRS) score (0-2) had lower mean PLR value than patients with unfavorable mRS (p<0.001). (B) Comparison of PNR between groups showed significantly higher PNR in patients with favorable mRS (p<0.001). (C) The mean value of PWR was higher in favorable mRS patients, compared with unfavorable mRS patients (p=0.009).

Fig. 2.

Receiver operating characteristic (ROC) curve of platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR) on prognosis of patients who underwent MT for LAO. The optimal cutoff value of PLR level to discriminate between favorable (0-2) and unfavorable (3-6) modified Rankin Scale (mRS) scores at 3 months was 145 (area under the curve (AUC) 0.663, 95% CI 0.611–0.715; p<0.001). In addition, a PNR value of 41 (AUC 0.616, 95% CI 0.572-0.660; p=0.001) and PWR value of 25 (AUC 0.583, 95% CI 0.521-0.645; p=0.006) were identified as the optimal cutoff values to predict favorable 3 months mRS after MT, respectively. MT, mechanical thrombectomy; CI, confidence interval

Table 1.

Baseline characteristics and outcomes of patients, according to functional outcomes at 3 month

Variables Favorable Unfavorable p-value
Demographics
 Number of patients (%) 240 (55.6) 192 (44.4)
 Age, mean±SD 66.0±13.5 73.4±11.8 <0.001*
 Men, n (%) 136 (56.7) 97 (50.5) 0.203
Risk factors, n (%)
 Hypertension 136 (56.7) 117 (60.9) 0.279
 Diabetic mellitus 61 (25.4) 52 (27.1) 0.695
 Atrial fibrillation 86 (35.8) 76 (39.6) 0.287
 Coronary artery disease 41 (17.1) 26 (13.5) 0.138
 Prior stroke or TIA 26 (10.8) 30 (15.6) 0.141
 Smoking 47 (19.6) 39 (20.3) 0.850
 Dyslipidemia 104 (43.3) 74 (38.5) 0.315
 Body mass index ≥25 kg/m2 65 (27.1) 55 (28.6) 0.719
Stroke etiology, n (%)
 Cardio-embolic 104 (43.3) 76 (39.6) 0.401
 Atherosclerosis 75 (31.3) 70 (36.5) 0.374
 Dissection 4 (1.7) 2 (1.0) 0.288
 Other or undetermined 57 (23.8) 44 (22.9) 0.408
Occlusion site, n (%)
 Middle cerebral artery 138 (57.5) 99 (51.6) 0.327
 Distal internal carotid artery 42 (17.5) 41 (21.4) 0.309
 Proximal internal carotid artery 34 (14.2) 31 (16.1) 0.411
 Anterior cerebral artery 4 (1.7) 3 (1.6) 0.889
 Posterior circulation 22 (9.2) 18 (9.4) 0.851
Laboratory findings, mean±SD
 Red blood cells, ×1012/L 4.45±0.75 4.55±1.61 0.363
 White blood cells, ×109/L 8.35±3.29 9.68±3.73 0.104
 Neutrophils, ×109/L 6.77±3.38 7.43±3.81 0.032*
 Lymphocytes, ×109/L 1.99±1.03 1.72±1.37 0.030*
 Monocytes, ×109/L 0.56±0.24 0.61±0.29 0.251
 Hemoglobin, g/dL 13.79±1.97 13.55±2.79 0.299
 Hematocrit, % 42.09±16.79 39.41±13.28 0.129
 Platelets, ×109/L 229.1±86.6 220.1±64.5 0.232
 PLR 135.0±120.3 167.6±139.3 <0.001*
 PNR 47.1±24.6 35.4±22.4 <0.001*
 PWR 27.7±12.1 22.4±10.8 0.009*
 Prothrombin time, sec 13.4±5.78 13.6±6.28 0.421
 Activated partial thromboplastin time, sec 36.4±12.4 37.1±14.5 0.537
 High-sensitivity C-reactive protein, mg/L 0.65±1.65 1.18±2.51 0.010*
 Erythrocyte sedimentation rate, mm/h 19.4±16.9 22.7±19.8 0.107
 Total protein, g/dL 6.79±0.69 6.81±0.68 0.713
 Blood urea nitrogen (BUN), mg/dL 16.77±9.61 17.85±8.37 0.224
 Creatinine (Cr), mg/dL 0.86±0.45 0.90±0.67 0.500
 BUN/Cr ratio 20.62±12.71 21.04±10.39 0.686
 HbA1c, % 6.20±1.23 6.19±1.24 0.947
 Serum glucose, mg/dL 148.8±61.4 154.8±58.3 0.299
 Total cholesterol, mg/dL 178.1±49.9 177.1±41.6 0.831
 HDL-C, mg/dL 51.1±21.2 48.9±19.5 0.244
 LDL-C, mg/dL 104.5±34.8 105.2±31.5 0.837
 Triglyceride, mg/dL 141.1±103.4 124.0±80.1 0.244
Pre-interventional details
 Left hemisphere stroke, n (%) 139 (57.9) 102 (53.1) 0.319
 Intravenous thrombolysis, n (%) 84 (35.0) 73 (38.0) 0.517
 ASPECTS, median (IQR) 9 [8-10] 8 [6-10] 0.014*
 Initial NIHSS, mean±SD 8.1±5.1 13.9±6.6 <0.001*
 Sx to puncture time (min), mean±SD 212±98 298±133 <0.001*
Procedure detail
 Procedure time (min), mean±SD 34±18 59±36 0.002*
 Successful recanalization, n (%) 235 (97.9) 172 (89.6) <0.001*
 First pass reperfusion, n (%) 105 (43.8) 62 (32.3) 0.015*
Clinical outcomes, n (%)
 Symptomatic intracerebral hemorrhage 4 (1.7) 27 (14.1) <0.001*
 Hemorrhagic transformation 37 (15.4) 62 (32.3) <0.001*
 Mortality at 3 months 0 (0.0) 39 (20.3) <0.001*

Data are presented as n (%), mean±SD and median [IQR].

*

Statistically significant

SD, standard deviation; TIA, transient ischemic attack; PLR, platelet-to-lymphocyte ratio; PNR, platelet-to-neutrophil ratio; PWR, platelet-to-white blood cell ratio; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ASPECTS, alberta stroke program early CT score; IQR, interquartile range; NIHSS, national institutes of health stroke scale; Sx, symptom

Table 2.

Predictors of favorable clinical outcome in univariate and multivariate logistic regression analyses

Univariate
Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age (<70 yr) 1.58 (1.02-2.07) 0.012* 1.39 (1.04-1.63) 0.022*
Gender (male) 1.19 (0.68-2.06) 0.536
Hypertension 0.77 (0.44-1.35) 0.363
Diabetic mellitus 0.92 (0.49-1.71) 0.802
Atrial fibrillation 1.11 (0.63-1.94) 0.715
Coronary artery disease 1.68 (0.70-2.22) 0.241
Prior stroke or TIA 0.54 (0.24-1.18) 0.224
Dyslipidemia 1.15 (0.68-1.96) 0.594
Body mass index ≥25 kg/m2 0.86 (0.48-1.53) 0.613
PLR (<145) 1.44 (1.04-2.20) 0.010* 1.29 (1.06-2.06) 0.016*
PNR (>41) 1.32 (1.08-1.88) 0.012* 1.22 (1.10-1.62) 0.022*
PWR (>25) 1.21 (1.06-1.92) 0.039* 1.14 (0.82-2.02) 0.075
hsCRP (<1 mg/L) 1.22 (1.04-1.64) 0.042* 1.18 (0.96-1.82) 0.068
Intravenous thrombolysis 0.74 (0.43-1.22) 0.261 1.64 (0.82-3.42) 0.202
ASPECTS (>8) 2.42 (1.44-5.08) 0.008* 2.24 (1.64-4.08) 0.012*
Initial NIHSS (<8) 3.76 (2.22-6.34) <0.001 3.64 (2.21-6.01) 0.002
Successful recanalization 2.42 (1.03-5.22) 0.027 2.27 (1.17-4.43) 0.036
First pass reperfusion 1.25 (0.54-1.72) 0.157 1.22 (0.68-1.66) 0.180
sICH 0.14 (0.03-0.54) 0.002 0.14 (0.04-0.52) 0.003
Hemorrhagic transformation 0.87 (0.68-1.74) 0.227
*

Statistically significant

OR, odds ratio; CI, confidence interval; TIA, transient ischemic attack; PLR, platelet-to-lymphocyte ratio; PNR, platelet-to-neutrophil ratio; PWR, platelet-to-white blood cell ratio; hsCRP, high-sensitivity C-reactive protein; ASPECTS, alberta stroke program early CT score; NIHSS, national institutes of health stroke scale; sICH, symptomatic intracerebral hemorrhage

Table 3.

Predictors of 3 month mortality in univariate and multivariate logistic regression analyses

Univariate
Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age (< 70 yr) 0.25 (0.09-0.68) 0.007* 0.31 (0.12-0.76) 0.010*
Gender (male) 1.56 (0.66-3.72) 0.310
Hypertension 1.60 (0.67-3.82) 0.289
Diabetic mellitus 0.54 (0.19-1.49) 0.238
Atrial fibrillation 0.83 (0.35-1.98) 0.682
Coronary artery disease 1.29 (0.47-3.51) 0.615
Prior stroke or TIA 1.17 (0.40-3.43) 0.767
Dyslipidemia 0.97 (0.39-2.09) 0.818
Body mass index ≥25 kg/m2 0.81 (0.24-2.74) 0.742
PLR (<145) 0.81 (0.74-0.88) 0.010* 0.83 (0.76-0.92) 0.018*
PNR (>41) 0.89 (0.80-0.98) 0.034* 0.94 (0.82-0.96) 0.042*
PWR (>25) 0.88 (0.80-1.38) 0.082 1.04 (0.89-1.36) 0.135
hsCRP (<1 mg/L) 0.72 (0.62-0.98) 0.014* 0.82 (0.68-1.10) 0.082
Intravenous thrombolysis 0.98 (0.42-2.27) 0.973
ASPECTS (>8) 0.60 (0.42-1.44) 0.130 0.61 (0.44-1.28) 0.144
Initial NIHSS (<8) 0.36 (0.15-0.88) 0.025* 0.37 (0.16-0.86) 0.021*
Successful recanalization 3.18 (0.51-6.99) 0.220
First pass reperfusion 0.54 (0.26-1.14) 0.217
sICH 2.52 (1.05-6.05) 0.038* 2.23 (1.02-4.96) 0.040*
Hemorrhagic transformation 1.03 (0.44-2.44) 0.394
*

Statistically significant

OR, odds ratio; CI, confidence interval; TIA, transient ischemic attack; PLR, platelet-to-lymphocyte ratio; PNR, platelet-to-neutrophil ratio; PWR, platelet-to-white blood cell ratio; hsCRP, high-sensitivity C-reactive protein; ASPECTS, alberta stroke program early CT score; NIHSS, national institutes of health stroke scale; sICH, symptomatic intracerebral hemorrhage