Platelet-to-neutrophil ratio predicts hemorrhagic transformation and unfavorable outcomes in acute ischemic stroke with intravenous thrombolysis

Abstract

BACKGROUND

Acute ischemic stroke (AIS) retains a notable stance in global disease burden, with thrombolysis via recombinant tissue plasminogen activator (rtPA) serving as a viable management approach, albeit with variable outcomes and the potential for complications like hemorrhagic transformation (HT). The platelet-to-neutrophil ratio (P/NR) has been considered for its potential prognostic value in AIS, yet its capacity to predict outcomes following rtPA administration demands further exploration.

AIM

To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.

METHODS

Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed. The relationship between P/NR and clinical outcomes [early neurological deterioration (E-ND), HT, delayed ND (D-ND), and 3-mo outcomes] was scrutinized.

RESULTS

Notable variables, such as age, diabetes, and stroke history, exhibited statistical disparities when comparing patients with and without E-ND, HT, D-ND, and 3-mo outcomes. P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3% sensitivity and a 52.5% specificity for 90-d outcomes. P/NR prognostic accuracy was statistically significant for 90-d outcomes [area under the curve (AUC) = 0.562], D-ND (AUC = 0.584), and HT (AUC = 0.607).

CONCLUSION

P/NR demonstrated an association with adverse 3-mo clinical outcomes, HT, and D-ND in AIS patients post-rtPA administration, indicating its potential as a predictive tool for complications and prognoses. This infers that a diminished P/NR may serve as a novel prognostic indicator, assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.

Key Words: Acute ischemic stroke; Platelet-to-neutrophil ratio; Prognosis; Hemorrhagic transformation; Recombinant tissue plasminogen activator; Thrombolysis; Clinical outcomes

Core Tip: The study explored the prognostic value of the platelet-to-neutrophil ratio (P/NR) in patients with acute ischemic stroke (AIS) who underwent thrombolysis with recombinant tissue plasminogen activator (rtPA). It aimed to determine if P/NR could predict hemorrhagic transformation and clinical outcomes following rtPA treatment. An optimal P/NR cutoff value was identified for predicting 90-d outcomes with moderate sensitivity and specificity. The study concluded that P/NR is associated with negative 3-mo outcomes, suggesting it could be a useful indicator for predicting risks post-rtPA treatment in AIS patients.

INTRODUCTION

Stroke has perpetually maintained a predominant position, ranking within the top three, regarding disease burden over the past two decades, as assessed through disability-adjusted life-years (DALYs)[1,2]. The gravity of cerebral infarction, witnessed during acute ischemic stroke (AIS), bears a correlation with the disease's burden[3]. Ensuring successful AIS management proves pivotal in mitigating its associated burdens[4]. Cardioembolic and atherothrombotic strokes are the subtypes of ischemic infarct associated with the highest in-hospital mortality. The short-term prognosis for patients with these types of strokes is poorer compared to other ischemic stroke subtypes[5]. Despite the absence of a mortality reduction, intravenous thrombolysis employing recombinant tissue plasminogen activator (rtPA) has been substantiated to attenuate the burden in AIS[6]. Regrettably, merely 50% of patients manifest significantly favorable outcomes post intravenous rtPA administration[7]. Stroke survivors, perpetuating suboptimal outcomes subsequent to treatment, endure the remainder of their existence with disadvantageous DALYs[8]. A salient progenitor of unfavorable outcomes resides in complications attributed to intracranial hemorrhagic transformation (HT) in association with intravenous rtPA[9]. A multitude of predictive instruments for outcomes in AIS, following treatment with intravenous rtPA, have permeated clinical practice; nevertheless, the parameters encapsulated within each tool exhibit variance[10,11].

In the AIS pathogenesis, platelet activation and aggregation emerge as critical elements. Amidst pathological circumstances, an excessive activation and aggregation of platelets can precipitate thrombosis and vascular occlusion, thereby instigating ischemic stroke or heart disease[12]. A plethora of studies have authenticated a decrement in platelet count within the circulatory system of AIS patients, whereas the platelet distribution width and mean platelet volume experience an elevation[13]. The immune response is recognized as imperative in the pathological alterations observed in AIS. Ischemic and anoxic brain tissue instigates the infiltration of peripheral blood leukocytes into the afflicted area. Neutrophils, the initial cells to be recruited into the brain following a stroke, discharge inflammatory mediators within the ischemic brain area, exacerbate brain damage[14] and foster the incidence of ischemia by inducing thrombosis via various mechanisms, such as interfacing with platelets, coagulation factors, and discharging proteases[15]. The platelet-to-neutrophil ratio (P/NR) emerges as a novel biomarker that amalgamates platelets and neutrophil counts. Contrasting with singular platelet and neutrophil counts, P/NR mirrors the severity of both thrombosis and inflammation, elucidating the liaison between the two processes. Within the realm of stroke, a recent study posited that the level of P/NR upon admission is associated with the prognosis of AIS patients[16]. Furthermore, another study advocated that P/NR surpasses other complete blood count ratios in prognosticating an adverse outcome in AIS patients[17]. Within this retrospective study, our objective was to illustrate the clinical value of P/NR in prognosticating the outcome in AIS patients who have been treated with intravenous rtPA.

MATERIALS AND METHODS

Study population

This retrospective study was conducted utilizing data procured from Thammasat University Hospital (TUH). The patient cohort comprised individuals diagnosed with AIS who underwent intravenous thrombolysis treatment, specifically utilizing intravenous rtPA, in adherence to the TUH protocol between January 2018 and June 2021. A complete blood count (CBC) was mandated before confirming the decision to administer intravenous rtPA[18].

Inclusion criteria: Patients formally diagnosed with AIS who met the criteria for and consequently received intravenous rtPA treatment within 4.5 h of stroke onset, in line with the stroke fast-track criteria established by TUH. Age range between 18 years and 85 years.

Exclusion criteria: Patients with a history of infection or surgery within the preceding 2 wk. An underlying disease condition such as malignancy, rheumatoid arthritis, or connective tissue disease. Chronic liver disease (Child-Pugh Score > B). Chronic kidney disease (serum creatinine > 2.0 mg/dL). Prior abnormalities in platelet and white blood cell counts. Ultimately, 418 patients were incorporated into the study, forming the basis for subsequent analysis and findings.

Ethical approval and methodological adherence

The Human Research Ethics Committee of Thammasat University (Medicine) bestowed approval for this study and granted a waiver for the requirement of informed consent, under approval number: 284/2564. All methodologies employed throughout the study adhered scrupulously to pertinent guidelines and regulations.

Data collection

Data procurement entailed an assessment by proficient clinicians, predicated on clinical manifestations, to verify alignment with the diagnostic criteria for acute stroke. Stroke severity upon admission was gauged using the National Institute of Health Stroke Scale (NIHSS). To exclude hemorrhagic stroke, all patients underwent emergent imaging via computerized tomography (CT) scan or magnetic resonance imaging (MRI) prior to intravenous rtPA administration. Pre-rtPA intravenous CBC was obtained. Additionally, baseline clinical attributes, inclusive of alternative laboratory examinations within 24 h of admission [e.g., fasting blood glucose and low-density lipoprotein (LDL)] and demographic data, were amassed for all patients[19].

Evaluation standard

Criteria were as follows: Hypertension was characterized by recurrent systolic blood pressure readings ≥ 140 mmHg upon admission or antecedent hypertension history. Diabetes encapsulated either a prior diagnosis or admission with diabetes mellitus, and either fasting plasma glucose ≥ 126 mg/dL or HbA1C ≥ 6.5%. Atrial fibrillation (AF) required precedent AF episodes or admission-time AF electrocardiogram recordings. Hyperlipidemia entailed hyperlipidemia history or admission with dyslipidemia, and either LDL ≥ 100 mg/dL or triglyceride ≥ 150 mg/dL[20].

Infarct volume was calculated employing 418 cases examined via CT scans or MRI, utilizing the formula 0.5 × a × b × c (where a is the maximum longitudinal diameter, b is the maximum transverse diameter perpendicular to a, and c denotes 10 mm slices with infarction), with volumes < 5 cm³ and ≥ 5 cm³ defining small and large infarct volumes, respectively[21].

Outcomes

Clinical outcomes encompassed early neurological deterioration (E-ND), HT, delayed ND (D-ND), and 3-mo poor outcomes. HT was delineated as any perceptible hemorrhage discerned on brain CT or MRI within 24 h post-thrombolysis, categorized via the Heidelberg Bleeding Classification[22]. E-ND was delineated as an augmentation of ≥ 4 points in NIHSS scores or death within 24 hours subsequent to intravenous thrombolysis. D-ND and 3-mo clinical outcomes were appraised utilizing the modified Rankin Scale (mRS), with D-ND and poor 3-mo outcomes defined as mRS scores of 3–6 at discharge (24 h to 7 d) and 3 mo post-onset, respectively.

Statistical analysis

Analytical procedures were executed utilizing the Statistical Program for Social Sciences (SPSS), version 22.0 (IBM, West Grove, PA, United States). The Mann-Whitney U-test facilitated the evaluation of disparities between two groups for variables demonstrating a nonparametric distribution, while the Chi-square test was employed to discern variations between categorical variables. Continuous and categorical variables were depicted utilizing medians with interquartile ranges (IQR) and percentages, respectively. The prognostic impact of P/NR was appraised by employing the receiver operating characteristic (ROC) curve, with a P-value < 0.05 establishing statistical significance in all comparative group analyses.

RESULTS

Demographic and clinical overview of the study population

This investigation encompassed 418 patients, comprising 169 females (40.4%) and 249 males (59.6%), with a mean age of 64.5 years (range: 53-72 years) and a mean NIHSS score upon admission of 10 (IQR: 6-16). The predominant risk factors identified were hypertension (71.5%), hyperlipidemia (66%), and diabetes (33.7%). The mean time from stroke onset to intravenous rtPA administration was 170 min (IQR: 124-218 minutes). Laboratory findings included hemoglobin at 13.3 g/dL (IQR: 12.2-14.4) and white blood cell count at 8.4 × 10⁹/L (IQR: 6.81-10.51 × 10⁹/L), among other parameters. Antihypertensive therapy was the most prevalent current medication at 45.6%. Patient outcomes following intravenous rtPA at various time points (24 h, 24 h to 7 d, and 3 mo post-thrombolysis) were also analyzed. Of note, 24 (5.7%) exhibited E-ND, while 75 (18%) manifested HT within the initial 24 h following intravenous rtPA. Twelve patients (2.87%) died in the hospital. Of these, eight patients' deaths were due to neurologic complications.

Correlation between P/NR and clinical outcomes

Eligible patients were stratified into groups according to the presence or absence of distinct clinical outcomes (E-ND, HT, D-ND, and 3-mo outcomes). In the E-ND assessment, statistically significant disparities were observed between groups with and without E-ND in terms of age, diabetes prevalence, current alcohol consumption, baseline blood glucose, and infarct volume, as further detailed. For instance, a statistically higher age was observed in the E-ND group (70 vs 64; P = 0.045).

Differences were also evident when comparing patients with and without HT. Variables that demonstrated statistical variance encompassed previous stroke, stroke etiology, NIHSS upon admission, and LDL, among others. For instance, individuals without a prior stroke manifested a higher proportion of HT than those with a previous stroke (13% vs 4%; P = 0.027).

Differences in clinical characteristics between the presence and absence of D-ND highlighted variables such as age, sex, and hypertension as statistically significant. For example, the D-ND group exhibited a higher mean age than the non-D-ND group (67 vs 60 years; P < 0.001).

In distinguishing between favorable and unfavorable 3-mo clinical outcomes, statistically significant variations were found in variables such as age, sex, and hypertension. Notably, patients with poor 3-mo outcomes had a mean age of 69 years, contrasted with 60 years for those with favorable outcomes (P < 0.001).

The ROC and area under the curve (AUC) analyses for P/NR in prognosticating 90-d outcomes post-ischemic stroke following intravenous thrombolysis revealed an optimal P/NR cutoff value of 43.4, with a 60.3% sensitivity and a 52.5% specificity, 32.86% (95%CI: 26.56-39.17) positive predictive value and a 77.45% (95%CI: 71.72-83.19) negative predictive value. P/NR demonstrated a statistically significant prognostic accuracy of 56.2% for 90-d outcomes (AUC = 0.562, 95%CI: 0.501-0.624, P = 0.048).

ROC curves also provided prognostic insights for P/NR in relation to D-ND and HT post-ischemic stroke following intravenous thrombolysis. Notably, the P/NR offered a 58.4% accurate prognostication for D-ND (AUC = 0.584, 95%CI: 0.504-0.664, P = 0.044), and a 60.7% accurate prognostication for HT (AUC = 0.607, 95%CI: 0.535-0.678, P = 0.004).

These findings, along with further relevant data, are articulated within Figure 1, Tables 1, 2, 3, and 4, and Supplementary Table 1.

Figure 1 Receiver operating characteristic curve. A: Receiver operating characteristic curve (ROC) of platelets to neutrophil ratio (P/NR) for predicting 90-d outcome in acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA); B: ROC of P/NR for predicting delay neurological deterioration in acute ischemic stroke after intravenous rtPA; C: ROC of P/NR for predicting hemorrhagic transformation in acute ischemic stroke after intravenous rtPA; D: ROC of P/NR for predicting early neurological deterioration in acute ischemic stroke after intravenous rtPA.

Table 1 Clinical characteristics of the study population.

Characteristics	Number
Age in yr	64.5 (53-72)
Sex
Male	249 (59.6)
Female	169 (40.4)
Risk factor
Hypertension	299 (71.5)
Dyslipidemia	276 (66)
Diabetes mellitus	141 (33.7)
Atrial fibrillation/atrial flutter	102 (24.4)
Old stroke	47 (11.2)
Current smoking	73 (17.5)
Current alcohol drinking	42 (10)
Etiology
Other determined or undetermined	177 (42.3)
Cardioembolic	102 (24.4)
Small-artery occlusion	94 (22.5)
Large-artery atherosclerosis	42 (10)
Medication before stroke onset
Antihypertensive therapy	202 (48.3)
Antiplatelet therapy	81 (18.3)
Hypoglycemic therapy	121 (27.3)
Time for stroke onset to intravenous rtPA infusion in min	170.05 (124-218.25)
Infarct volume in mL	3.27 (0.58-24.24)
Hemorrhagic transformation
No	343 (82)
Yes	75 (82)
PH1	29 (82)
PH2	27 (6.1)
HI1	12 (2.7)
HI2	7 (1.6)

Data are n (%)/median (25^th-75^th percentiles). HI: Hemorrhagic infarct; PH: Parenchymal hemorrhage; rtPA: Recombinant tissue plasminogen activator.

Table 2 Clinical characteristics of the study population (continued).

Characteristics	Number
Baseline blood glucose in mg%	110 (96-141)
Laboratory tests
Hb	13.3 (12.2-14.4)
WBC as 109/L	8.4 (6.81-10.51)
Platelets as 109/L	227 (192-278)
Neutrophil as 109/L	5.14 (3.8-7.06)
Lymphocyte as 109/L	1.93 (1.36-2.7)
P/NR	43.73 (32.0-59.04)
PLR	115.33 (87.17-170.64)
NLR	2.56 (1.61-4.52)
PWR	27.07 (21.4-33.99)
LDL	114.5 (89-143)
NIHSS on admission	10 (6-16)
NIHSS score on discharge date (day 1-7)	5 (1-10)
Outcome events
Increase NIHSS from baseline or death within 7 d after IV rt-PA
Poor outcome (≥ 4 score)	24 (5.7)
Good outcome (< 4 score)	394 (94.3)
mRS on admission	5 (3.75-5)
Poor outcome (3-6)	348 (83.3)
Good outcome (0-2)	70 (16.7)
mRS on discharge date (day 1-7)	3 (1-4)
Poor outcome (3-6)	236 (56.5)
Good outcome (0-2)	182 (43.5)
mRS at 3 mo	2 (0-4)
Poor outcome (3-6)	168 (40.2)
Good outcome (0-2)	250 (59.8)

Data are n (%)/median (25^th-75^th percentiles). Hb: Hemoglobin; LDL: Low density lipoprotein; mRS: Modified Rankin Scale; NIHSS: National Institute of Health Stroke Scale; NLR: Neutrophil-to-lymphocyte ratio; P/NR: Platelet-to-neutrophil ratio; PLR: Platelet-to-lymphocyte ratio; WBC: White blood cell.

Table 3 Clinical characteristics of patients according to presence/absence of early neurological deterioration and hemorrhagic transformation after intravenous recombinant tissue plasminogen activator treatment.

Variables	Total, n = 418	No E-ND, n = 394	E-ND, n = 24	P value	No HT, n = 342	HT, n = 75	P value
Age in yr	64.5 (53-72)	64 (52-71)	70 (58.75-77.25)	0.0451	65 (53-72)	64 (52-74)	0.9391
Sex
Male	249 (59.6)	237 (60.2)	12 (50)	0.3252	206 (60.2)	42 (56.0)	0.4992
Female	169 (40.4)	157 (39.8)	12 (50)		136 (39.8)	33 (44.0)
Risk factor
Hypertension	299 (71.5)	279 (71.2)	20 (83.3)	0.1982	245 (72.1)	53 (70.7)	0.8082
Dyslipidemia	276 (66.0)	261 (66.9)	15 (62.5)	0.6552	223 (65.8)	52 (70.3)	0.4582
Diabetes mellitus	141 (33.7)	126 (32.1)	15 (62.5)	0.0022	114 (33.4)	26 (34.7)	0.8382
Atrial fibrillation/ atrial flutter	102 (24.4)	97 (24.6)	5 (20.8)	0.6752	81 (23.7)	21 (28.0)	0.4312
Old stroke	47 (11.2)	44 (11.3)	3 (12.5)	0.8522	44 (13.0)	3 (4.0)	0.0272
Current smoking	73 (17.5)	70 (82.4)	3 (100)	0.4242	62 (83.8)	10 (76.9)	0.5462
Current alcohol drinking	42 (10.0)	42 (91.3)	0 (0)	0.0032	37 (90.2)	5 (83.3)	0.6082
Etiology
Other determined or undetermined	177 (42.3)	161 (41.2)	16 (66.7)	0.0052	143 (42.1)	34 (45.3)	< 0.0012
Cardioembolic	102 (24.4)	100 (25.6)	2 (8.3)		73 (21.5)	29 (38.7)
Small-artery occlusion	94 (22.5)	93 (23.8)	1 (4.2)		91 (26.8)	3 (4.0)
Large-artery atherosclerosis	42 (10)	37 (9.5)	5 (20.8)		33 (9.7)	9 (12.0)
Medication
Antihypertensive therapy	202 (45.6)	75 (19.0)	6 (25.0)	0.4732	165 (48.2)	37 (49.3)	0.8642
Antiplatelet therapy	81 (18.3)	191 (48.5)	11 (45.8)	0.8012	63 (18.4)	18 (24.0)	0.2692
Hypoglycemic therapy	121 (27.3)	111 (28.2)	10 (41.7)	0.162	96 (28.2)	25 (33.3)	0.3712
Infarct volume in mL	3.27 (0.58-24.24)	2.76 (0.45-20.25)	34.42 (5.57-303.93)	< 0.0011	2.67 (0.43-16.88)	13.99 (1.11-73.07)	0.3891
Time for stroke onset to intravenous rtPA infusion in min	170.05 (124-218.25)	170 (122-217)	180.5 (147.5-232.25)	0.1571	172 (124.85-218.25)	160 (124-219)	0.5161

¹Mann Whitney U test.

²χ² test.

Data are n (%)/median (25^th-75^th percentiles). E-ND: Early neurological deterioration; HT: Hemorrhagic transformation; rtPA: Recombinant tissue plasminogen activator.

Table 4 Clinical characteristics of patients according to presence/absence of delayed neurological deterioration and 3-mo outcome after intravenous recombinant tissue plasminogen activator treatment.

Variables	Total, n = 418	No D-ND, n = 182	D-ND, n = 236	P value	Good 3-months, n = 250	Poor 3-months, n = 168	P value
Age in yr	64.5 (53-72)	60 (49-67.25)	67 (58-76.75)	< 0.0011	60 (50-68)	69 (61-75)	< 0.0011
Sex
Male	249 (59.6)	120 (65.9)	129 (54.7)	0.022	162 (64.8)	87 (51.8)	0.0082
Female	169 (40.4)	62 (34.1)	107 (45.3)		88 (35.2)	81 (48.2)
Risk factor
Hypertension	299 (71.5)	114 (62.6)	185 (79.1)	< 0.0012	163 (65.2)	136 (81.9)	< 0.0012
Dyslipidemia	276 (66.0)	113 (62.8)	163 (69.7)	0.1412	162 (65.3)	114 (68.7)	0.4782
Diabetes Mellitus	141 (33.7)	55 (30.4)	86 (36.4)	0.1952	73 (29.3)	68 (40.5)	0.0182
Atrial fibrillation/atrial flutter	102 (24.4)	40 (22.0)	62 (26.3)	0.3112	53 (21.2)	49 (29.2)	0.0632
Old stroke	47 (11.2)	16 (8.8)	31 (13.2)	0.162	24 (9.7)	23 (13.7)	0.212
Current smoking	73 (17.5)	38 (86.4)	35 (79.5)	0.3952	52 (85.2)	21 (77.8)	0.392
Current alcohol drinking	42 (10.0)	20 (95.2)	22 (84.6)	0.242	30 (88.2)	12 (92.3)	0.6852
Etiology
Other determined or undetermined	177 (42.3)	69 (38.3)	108 (46.0)	0.0042	93 (37.5)	84 (50.3)	0.0022
Cardioembolic	102 (24.4)	51 (28.3)	51 (21.7)		70 (28.2)	32 (19.2)
Small-artery occlusion	94 (22.5)	50 (27.8)	44 (18.7)		66 (26.6)	28 (16.8)
Large-artery atherosclerosis	42(10)	10 (5.6)	32 (13.6)		19 (7.7)	23 (13.8)
Medication
Antihypertensive therapy	202 (45.6)	81 (44.5)	121 (51.3)	0.172	111 (44.4)	91 (54.2)	0.052
Antiplatelet therapy	81 (18.3)	31 (17.0)	50 (21.2)	0.2872	44 (17.6)	37 (22.0)	0.2622
Hypoglycemic therapy	121 (27.3)	53 (29.1)	68 (28.9)	0.9672	71 (28.5)	50 (29.8)	0.7832
Infarct volume in mL	3.27 (0.58-24.24)	1.16 (0.05-7.88)	7.61 (1.53-63.41)	0.361	1.46 (0.13-7.93)	16.62 (2.51-103.09)	0.0131
Time for stroke onset to intravenous rtPA infusion in min	170.05 (124-218.25)	182 (0-125)	167.5 (120-219.5)	0.5281	173.5 (125-218)	166.5 (120-220)	0.3061

¹Mann Whitney U test.

²χ² test.

Data are n (%)/median (25^th-75^th percentiles). D-ND: Delayed neurological deterioration; rtPA: Recombinant tissue plasminogen activator.

DISCUSSION

The investigation discerned a pertinent association between the P/NR and adverse 3-mo clinical outcomes, HT, and D-ND in patients experiencing AIS post-intravenous administration of rtPA. A diminished P/NR was discernibly correlated with unfavorable outcomes, positioning P/NR as a potential novel prognostic indicator for complications and prognoses in the stated patient demographic.

Despite P/NR being a relatively nascent parameter within stroke research, preliminary studies indicate its potential predictive capabilities for outcomes in AIS. A study conducted by Jin et al[16] posited P/NR as a singularly protective predictor for 90-d outcomes in AIS, also noting that lower P/NR was concomitant with short-term adverse outcomes. In a parallel vein, Wang et al[23] associated post-rtPA P/NR with E-ND, HT, D-ND, and suboptimal 3-mo outcomes, echoing the predictive utility of lower P/NR for worse outcomes. Matsuoka et al[24] suggested P/NR could indicate a hypercoagulable state, potentially inducing ischemic stroke related to gastric cancer. While P/NR is corroborated in several studies as being associated with thrombosis, its relationship with prognoses of patients receiving intravenous rtPA has not been comprehensively explored[25].

Insights from existing research elucidate that platelet-neutrophil interactions play a pivotal role in inflammation and thrombosis, particularly during AIS[26]. The intravascular thrombosis and ensuing inflammatory response precipitate a reduction in platelets and a surge in neutrophils, cumulatively resulting in diminished P/NR levels. Accordingly, a rational deduction can be drawn that low P/NR levels are independently associated with adverse AIS outcomes.

Moreover, considering the thrombolysis combination, symptomatic intracranial hemorrhage potentially exacerbates symptoms. A plethora of studies have demonstrated that a synergy of decreased platelets and elevated neutrophils can contribute to symptomatic intracranial hemorrhage[27-29]. Gensicke et al[30] provided insights into the mechanistic link between poor outcomes and neutrophils, elucidating that the latter disrupts the blood-brain barrier by liberating matrix metalloproteinase-9 and augmenting reactive oxygen and nitrogen species[29,30]. The conglomeration of these findings substantiates the hypothesis that P/NR may serve as a viable prognostic predictor for patient outcomes.

The present study not only benefits from an ample sample size, ensuring enhanced reliability and persuasive power of results, but also distinguishes itself as one of the few concentrating on the correlation between P/NR and prognosis in AIS patients treated with intravenous rtPA. Nonetheless, the implications of the findings should be interpreted considering several limitations, including the retrospective nature of the study and potential unconsidered confounders. Furthermore, the solitary hospital data source may induce selection bias, P/NR levels were measured only at a single time point (upon admission), and no dynamic monitoring was conducted. Also, numerous pre-existing conditions and infections that influence inflammation could potentially impact the P/NR ratio.

CONCLUSION

In recapitulation, the findings elucidate that P/NR demonstrates an independent association with unfavorable 3-mo outcomes (mRS ≥ 3), HT, and D-ND. A lower P/NR level could potentially serve as a predictor for adverse outcomes, thereby offering a novel parameter that neurologists might employ for prognosticating stroke outcomes in clinical settings. Prospective studies encompassing larger sample sizes and dynamic P/NR monitoring are requisite for further exploration.

ACKNOWLEDGEMENTS

The authors wish to thank Prof. Paskorn Sritipsukho from the Center of Excellence in Applied Epidemiology, Thammasat University, for his help with biostatistical analysis.