NLR–FAR Index as a Prognostic Marker in Acute Ischemic Stroke: Biological Rationale, Current Evidence, and Clinical Translation (2015–2025)

Acute ischemic stroke (AIS) remains one of the most devastating neurological emergencies, accounting for the majority of stroke cases and imposing substantial global burdens of death, disability, dependency, and healthcare expenditure [1–4]. Although reperfusion strategies such as intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) have transformed acute stroke care, substantial heterogeneity persists in treatment response, hemorrhagic complications, infarct progression, neurological recovery, and long-term functional outcomes [5–9]. This heterogeneity reflects the complex interplay among vascular occlusion characteristics, collateral circulation, infarct core–penumbra dynamics, blood–brain barrier (BBB) integrity, systemic inflammation, thrombosis, endothelial activation, and patient-level physiological reserve [10–14].

 In recent years, there has been increasing interest in blood-based prognostic biomarkers that are inexpensive, rapidly available, and broadly accessible in emergency settings [15–18]. Such biomarkers are particularly attractive in AIS because clinical decisions are often made within narrow therapeutic windows, and advanced imaging or specialized assays may not always be available—especially in resource-constrained settings. Among the most studied candidates, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a robust inflammatory index associated with stroke severity, early neurological deterioration, hemorrhagic transformation, poor functional outcome, and mortality [19–27]. NLR captures two biologically meaningful processes: an increase in circulating neutrophils reflecting acute innate immune activation, and a relative reduction in lymphocytes reflecting stress-related immunosuppression and impaired adaptive immune balance [20,21,28].

Parallel to this, the fibrinogen-to-albumin ratio (FAR has gained attention as a composite marker integrating prothrombotic/inflammatory burden (fibrinogen) with nutritional, antioxidant, endothelial-stabilizing, and anti-inflammatory reserve (albumin) [29–35]. Fibrinogen is a key acute-phase reactant and coagulation substrate implicated in clot architecture, blood viscosity, platelet aggregation, endothelial dysfunction, and microvascular obstruction [36–39]. Albumin, conversely, is associated with antioxidant capacity, endothelial protection, modulation of blood rheology, and maintenance of oncotic balance; low albumin has been repeatedly associated with poor stroke outcomes [40–44]. FAR therefore represents a biologically coherent marker of “thrombo-inflammatory imbalance.”

 A more recent conceptual advance is the proposal of a combined NLR–FAR index, intended to unify two related but non-identical pathobiological domains: systemic inflammatory dysregulation (NLR) and coagulation–nutritional/hemostatic imbalance (FAR). This combined index is attractive because ischemic stroke is increasingly understood as a thromboinflammatory syndrome, rather than a purely vascular occlusive event [45–49]. By combining NLR and FAR, investigators aim to better capture the multidimensional host response that shapes infarct evolution, reperfusion injury, hemorrhagic risk, and recovery trajectories.

 However, despite growing enthusiasm, the literature remains uneven. NLR is supported by multiple meta-analyses and a substantial number of cohort studies, whereas FAR evidence is newer and less extensive. Most importantly, direct evidence on the combined NLR–FAR index is still very limited [50].

 Accordingly, this review critically examines the biological rationale, current evidence, clinical applications, and limitations of the NLR–FAR index in AIS. Particular emphasis is placed on the distinction between well-supported evidence for NLR, growing evidence for FAR, and still-emerging evidence for the combined NLR–FAR index. The goal is to provide a balanced, scientifically rigorous synthesis suitable for journal submission and future research framing.

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 Search strategy

Relevant literature was identified through structured searches of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar. Search terms included combinations of the following keywords and Medical Subject Headings (MeSH) where applicable:

•              “acute ischemic stroke”

•              “ischemic stroke”

•              “neutrophil to lymphocyte ratio” OR “NLR”

•              “fibrinogen to albumin ratio” OR “FAR”

•              “NLR-FAR index” OR “NLR–FAR”

•              “prognosis”

•              “functional outcome”

•              “mortality”

•              “hemorrhagic transformation”

•              “intravenous thrombolysis”

•              “endovascular thrombectomy”

•              “reperfusion therapy”

•              “biomarker”

•              “inflammation”

•              “thromboinflammation”

 Eligibility criteria

Included studies met the following criteria:

1.             Published between 2015 and 2025.

2.             Human studies involving acute ischemic stroke.

3.             Evaluated NLR, FAR, or a combined NLR–FAR index in relation to clinical outcomes.

4.             Reported at least one of the following outcomes: baseline stroke severity, early neurological deterioration, hemorrhagic transformation, symptomatic intracranial hemorrhage, discharge outcome, 30-day or 90-day functional outcome, mortality, or post-reperfusion outcomes.

5.             Study designs included observational cohort studies, case-control studies, systematic reviews, and meta-analyses.

 Exclusion criteria

The following were excluded:

•              Studies focusing solely on hemorrhagic stroke, transient ischemic attack, or mixed stroke populations without separable AIS data.

•              Non-English articles where adequate data extraction was not feasible.

•              Case reports, editorials, letters without primary data, and conference abstracts lacking sufficient methodological detail.

•              Pre-2015 publications.

 Data synthesis approach

Because of heterogeneity in study populations, biomarker timing, outcome definitions, cut-off values, and statistical modeling, a narrative critical synthesis was performed rather than a de novo quantitative meta-analysis. Greater evidentiary weight was assigned to:

•              multicenter cohorts,

•              reperfusion-focused analyses,

•              adjusted multivariable models, and

•              systematic reviews/meta-analyses.

 Methodological considerations

A central methodological challenge in this field is lack of standardization. NLR may be measured on admission, pre-thrombolysis, post-thrombolysis, or at delayed time points; FAR may be calculated using differing fibrinogen and albumin units; and the combined NLR–FAR index has not yet been uniformly defined across studies. Consequently, interpretation in this review prioritizes directional consistency and biological plausibility over absolute threshold values.

 Biological Basis of the NLR–FAR Index in Ischemic Stroke

AIS initiates a rapidly evolving cascade of sterile inflammation, coagulation activation, endothelial injury, microvascular dysfunction, and systemic stress responses [45–49,51–55]. The NLR–FAR index is biologically attractive because it integrates these interlocking domains.

 Neutrophils and ischemic brain injury

Neutrophils are among the earliest leukocytes mobilized after cerebral ischemia [20,21,52]. They infiltrate the ischemic territory through endothelial adhesion and transmigration, facilitated by upregulated adhesion molecules, chemokines, and BBB disruption [52–55]. Once activated, neutrophils contribute to injury via:

•              release of reactive oxygen species (ROS),

•              proteolytic enzymes such as matrix metalloproteinase-9 (MMP-9),

•              neutrophil extracellular traps (NETs),

•              microvascular plugging and no-reflow phenomena, and

•              amplification of thromboinflammation [56–60].

These processes worsen reperfusion injury, promote hemorrhagic transformation, and enlarge infarct burden [57–61].

 Lymphocytes and stroke-induced immune dysregulation

In contrast, lymphocyte depletion after AIS may reflect stress-induced immunosuppression, sympathetic activation, hypothalamic–pituitary–adrenal axis effects, and apoptosis of adaptive immune cells [62–64]. Reduced lymphocyte counts may indicate impaired immunoregulatory balance, reduced neuroprotective immune signaling, and greater vulnerability to post-stroke infections [63–66]. Thus, a high NLR is not merely a marker of inflammation but also a marker of immune imbalance.

 Fibrinogen: coagulation substrate and inflammatory mediator

Fibrinogen is a liver-derived acute-phase glycoprotein central to coagulation, fibrin clot formation, and platelet aggregation [36–39]. In AIS, elevated fibrinogen is associated with:

•              increased plasma viscosity,

•              denser and more lysis-resistant clot structure,

•              endothelial activation,

•              platelet–leukocyte interaction,

•              enhanced thrombus propagation, and

•              impaired microcirculatory reperfusion [36–39,67–69].

 

Fibrinogen also contributes to inflammation by engaging integrins and toll-like receptor–related pathways, promoting leukocyte recruitment and vascular inflammation [68–70].

 Albumin: marker of systemic reserve and potential neurovascular protection

Albumin is a multifunctional plasma protein with antioxidant, anti-inflammatory, endothelial-stabilizing, and rheological properties [40–44,71]. Lower albumin levels in AIS may reflect:

•              poor nutritional reserve,

•              chronic inflammation or frailty,

•              hepatic dysfunction,

•              capillary leak/systemic stress, or

•              acute catabolic burden.

•             

Hypoalbuminemia has been associated with worse stroke severity, higher edema risk, increased infection, and poor functional recovery [41–44,72–74]. Although albumin infusion as a neuroprotective therapy has not translated successfully in large trials, endogenous albumin levels remain prognostically informative [75,76].

 

 

 

Figure 1: Pathophysiological framework of the proposed NLR–FAR index in acute ischemic stroke

 FAR as a thrombo-inflammatory balance marker

FAR combines two biologically opposed signals:

•              high fibrinogen = prothrombotic and proinflammatory state

•              low albumin = reduced physiological reserve and loss of protective buffering

 

A high FAR therefore may indicate an adverse internal milieu characterized by hypercoagulability + heightened inflammation + impaired resilience [29–35].

 Why a combined NLR–FAR index may be superior

The rationale for combining NLR and FAR lies in the concept of multidimensional host response profiling. NLR captures leukocyte-driven inflammatory and immunological disequilibrium, whereas FAR reflects hemostatic burden and reduced systemic reserve. Together, they may better approximate the “thromboinflammatory phenotype” that determines:

•              infarct progression,

•              reperfusion success,

•              no-reflow and microvascular failure,

•              hemorrhagic transformation risk, and

•              post-stroke recovery potential [45–50,56–60].

 

This mechanistic complementarity makes the NLR–FAR index biologically plausible, but biological plausibility alone is insufficient; robust clinical validation is still needed.

 Prognostic Significance of NLR in Acute Ischemic Stroke

Among blood-based inflammatory markers in AIS, NLR has the strongest evidence base.

 NLR and baseline stroke severity

Multiple studies have shown that higher admission NLR correlates with greater baseline NIHSS scores and larger infarct burden [19–27,77–82]. This relationship is consistent with the concept that more severe strokes generate stronger systemic inflammatory responses and greater neurovascular injury.

 NLR and functional outcome

Meta-analytic evidence supports a significant association between elevated NLR and poor functional outcome. A 2017 meta-analysis by Zhang et al. found that higher NLR was associated with poor 3-month functional outcome in AIS [22]. A 2019 cohort study with systematic review by Wang et al. further reinforced that admission NLR predicts poor outcomes after AIS [23]. The 2021 systematic review and meta-analysis by Li et al. demonstrated that elevated NLR is associated with unfavorable prognosis across stroke populations, including ischemic stroke subgroups [24]. In reperfusion-treated AIS, Wang et al. (2021) specifically showed that higher NLR in IVT-treated patients was associated with poor functional outcome and adverse events [25].

 NLR and hemorrhagic transformation

NLR has been linked to both hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH), particularly after IVT and EVT [22,25–27,83–86]. Mechanistically, neutrophil-mediated BBB injury, MMP-9 release, and reperfusion-related inflammatory amplification provide a plausible explanation [57–60]. This makes NLR especially relevant in thrombolysis/thrombectomy settings.

 NLR and mortality

Several observational studies and pooled analyses suggest that higher NLR predicts increased short-term mortality and poorer survival [22–27,87–90]. However, mortality associations are somewhat less consistent than functional outcome associations, likely because mortality is influenced by multiple downstream factors including age, comorbidities, infarct location, and complications.

 NLR in reperfusion-treated AIS

The prognostic utility of NLR may be particularly strong in reperfusion-treated populations. Sharma et al. (2022) reported in a systematic review and meta-analysis that both admission and delayed NLR were associated with worse outcomes after reperfusion therapy [26]. This is clinically important because reperfusion success does not always translate into favorable outcomes, and inflammatory burden may partially explain futile recanalization.

 Limitations of NLR alone

Despite its strengths, NLR has limitations:

•              non-specific elevation in infection, malignancy, trauma, or chronic inflammatory disease,

•              variability by timing of blood sampling,

•              lack of universal cut-offs, and

•              susceptibility to steroid use, physiological stress, and pre-existing immune conditions [17,18,91].

 

Thus, while NLR is among the best-supported stroke biomarkers, it is best viewed as an adjunctive prognostic marker rather than a standalone decision tool.

Table 1. Biological interpretation of components of the NLR–FAR framework in acute ischemic stroke

NLR = neutrophil-to-lymphocyte ratio; FAR = fibrinogen-to-albumin ratio; BBB = blood–brain barrier; NET = neutrophil extracellular trap; ROS = reactive oxygen species; HT = hemorrhagic transformation; sICH = symptomatic intracranial hemorrhage; mRS = modified Rankin Scale.

 

 Prognostic Significance of FAR in Acute Ischemic Stroke

Compared with NLR, FAR is a newer but increasingly studied biomarker in AIS.

 

Conceptual basis

FAR is particularly attractive because it captures both prothrombotic acute-phase activation (fibrinogen) and host reserve/anti-inflammatory buffering (albumin). This duality may be more informative than either analyte alone [29–35].

 

FAR and baseline stroke severity

Recent studies suggest that elevated FAR correlates with more severe initial neurological deficits and larger ischemic injury [29–35,92–95]. This may reflect greater thromboinflammatory burden and impaired collateral microcirculatory physiology.

 

FAR and functional disability

One of the most relevant studies is the 2023 analysis by Chen et al., which reported that higher FAR was associated with poorer 3-month functional prognosis in AIS patients after IVT [30]. This study strengthened the notion that FAR may outperform isolated fibrinogen or albumin measurements by integrating risk information.

FAR and mortality

Although mortality data are less abundant than for NLR, higher FAR has been associated with adverse clinical trajectories, including severe disability and, in some cohorts, increased mortality or composite poor outcome [29–35,92–96]. More robust multicenter data are still needed.

 

FAR and hemorrhagic transformation

FAR may be particularly relevant for hemorrhagic risk. In 2025, Liu et al. reported that post-thrombolysis FAR was associated with hemorrhagic transformation after IVT in AIS [31]. This is clinically important because post-reperfusion hemorrhagic complications remain a major determinant of poor outcome and may be influenced by coagulation–inflammation interactions.

 

FAR in reperfusion-treated patients

In EVT-treated populations, Ozdogru et al. (2024) demonstrated prognostic value of FAR in ischemic stroke patients undergoing mechanical thrombectomy [32]. Such data support the hypothesis that FAR may reflect clot biology, reperfusion injury susceptibility, and microvascular dysfunction after recanalization.

 

FAR compared with related ratio biomarkers

FAR belongs to a broader family of composite inflammatory ratios including C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) [33–35,97–100]. Its advantage is that fibrinogen directly reflects both inflammation and coagulation, potentially making it especially relevant to AIS pathophysiology.

 

Current limitations of FAR evidence

Despite promising signals, FAR evidence remains limited by:

·         predominance of single-center retrospective designs,

·         variability in assay timing (pre- vs post-reperfusion),

·         inconsistent unit standardization,

·         limited external validation, and

·         insufficient head-to-head comparisons with NLR or established clinical models [29–35].

 

Therefore, FAR should currently be considered a promising adjunctive biomarker, not yet a standardized clinical prognostic tool.

 

Table 2. Summary of representative post-2015 evidence on NLR in acute ischemic stroke

AIS = acute ischemic stroke; IVT = intravenous thrombolysis; NLR = neutrophil-to-lymphocyte ratio; sICH = symptomatic intracranial hemorrhage.

 

Emerging Evidence for the Combined NLR–FAR Index

Conceptual definition

The combined NLR–FAR index has been proposed as a composite biomarker that merges leukocyte-derived inflammatory status (NLR) with coagulation/nutritional-inflammatory balance (FAR). In currently available studies, the most commonly described approach is the product of NLR × FAR, though formal standardization has not yet been established [50].

 

Available clinical evidence

As of the 2015–2025 evidence window, direct literature on the combined NLR–FAR index in AIS is very limited. The most notable recent study is a 2026 provisionally accepted Frontiers in Neurology report by Meng et al., which falls outside the strict 2015–2025 final evidence window and therefore should not be treated as formal evidence in this final manuscript [50]. Nonetheless, it is scientifically informative as a near-future signal and suggests that the combined index may outperform NLR or FAR alone in EVT-treated AIS. Because this article is outside the requested time window and provisionally accepted, it should not be included in the strict reference base of a 2015–2025 submission.

 

Therefore, under strict evidence rules, the combined NLR–FAR index remains biologically compelling but not yet adequately validated in peer-reviewed post-2015 AIS literature up to 2025.

 

Indirect support from component biomarkers

The strongest argument for the combined index currently comes from the convergent evidence supporting its individual components:

·         NLR predicts stroke severity, poor 90-day outcome, HT, sICH, and mortality [22–27].

·         FAR predicts poor functional outcome, post-IVT HT, and adverse EVT outcomes [30–32].

 

This indirect support suggests that combining them may improve discrimination, calibration, or reclassification—but this remains a hypothesis until tested prospectively.

 

Why caution is essential

A major risk in the current literature is premature translation. Because the combined index appears intuitively superior, there is temptation to label it as “better” than NLR or FAR alone before sufficient external validation exists. Such claims should be avoided in a submission-ready review. At present, the appropriate scientific position is:

The NLR–FAR index is an emerging, biologically plausible composite marker with promising early signals, but it lacks sufficient direct evidence for routine clinical adoption in AIS.

Research value

Despite limited direct data, the NLR–FAR index is highly attractive for future studies because it is:

·         inexpensive,

·         rapidly available,

·         based on routine hospital laboratory tests,

·         mechanistically aligned with AIS thromboinflammation, and

·         potentially useful in both IVT and EVT pathways.

 

Table 3. Summary of representative post-2015 evidence on FAR in acute ischemic stroke

FAR = fibrinogen-to-albumin ratio; AIS = acute ischemic stroke; IVT = intravenous thrombolysis; EVT = endovascular thrombectomy.

 

Clinical Applications in Acute Stroke Management

If validated, the NLR–FAR framework may have several practical uses.

 

Early emergency department risk stratification

At hospital admission, a high NLR and/or FAR may identify patients at increased risk for:

·         severe baseline deficits,

·         malignant edema,

·         early neurological deterioration, and

·         poor functional outcome.

 

This could support more intensive monitoring and early multidisciplinary planning.

 

Reperfusion therapy prognostication

In IVT and EVT candidates, these biomarkers may help estimate:

·         risk of futile recanalization,

·         post-reperfusion inflammatory injury,

·         hemorrhagic transformation, and

·         need for closer post-procedural surveillance [25,26,30–32].

 

ICU and stroke unit monitoring

Serial measurement may be more informative than a single value. Dynamic rises in NLR or FAR after reperfusion could potentially reflect evolving BBB injury, infarct progression, infection, or systemic decompensation.

 

Counseling and rehabilitation planning

While biomarkers should never replace clinical and imaging assessment, they may enhance early communication regarding prognosis, discharge planning, and rehabilitation intensity—especially when integrated with age, NIHSS, imaging, and reperfusion metrics.

 

Utility in resource-limited settings

For settings where advanced imaging, perfusion software, or specialized biomarkers are not consistently available, NLR and FAR may offer pragmatic supplementary risk signals. This is particularly relevant in many real-world stroke systems across low- and middle-income countries.

 

Important caveat

At present, NLR and FAR can be considered adjunctive markers, but the combined NLR–FAR index is not yet ready for standalone clinical use. It should not be used to deny reperfusion therapy or alter guideline-based management outside research protocols.

 

Comparison with Other Inflammatory and Hemostatic Biomarkers

AIS biomarker research is crowded, and NLR–FAR must be interpreted relative to alternatives.

 

C-reactive protein (CRP) and CRP-to-albumin ratio (CAR)

CRP is widely available and prognostically relevant, but it may rise later and is highly nonspecific [97,98,101]. CAR has shown prognostic value in stroke and may be comparable to FAR in some contexts [99,100].

 

Platelet-to-lymphocyte ratio (PLR)

PLR reflects platelet activation plus immune status, but evidence is less consistent than NLR, and platelet counts may be influenced by numerous comorbid factors [102–104].

 

Lymphocyte-to-monocyte ratio (LMR)

LMR has emerging evidence, including recent meta-analytic support, but remains less established than NLR [105].

Systemic immune-inflammation index (SII)

SII (platelets × neutrophils / lymphocytes) may provide broader immune-thrombotic integration than NLR alone, but it is more complex and less familiar clinically [106–108].

 

D-dimer

D-dimer is highly relevant to thrombosis, cardioembolic stroke, cancer-associated stroke, and outcome prediction, but is less specific and influenced by age, infection, and malignancy [109–112].

 

Fibrinogen alone

Fibrinogen is directly relevant to thrombosis and inflammation, but FAR may be more informative because it contextualizes fibrinogen relative to albumin [29–35].

 

Albumin alone

Albumin is prognostically valuable but reflects a broad range of chronic and acute systemic conditions. FAR likely provides richer biological information than albumin in isolation [40–44].

 

Relative position of NLR–FAR

The putative advantage of NLR–FAR is that it combines:

·         leukocyte inflammatory activation,

·         adaptive immune suppression,

·         acute-phase coagulation burden, and

·         systemic reserve.

This multidomain structure may offer better clinical relevance than single analytes. However, until comparative model-performance studies are performed, superiority remains hypothetical.

Table 4. Practical strengths and limitations of the NLR–FAR index in acute ischemic stroke

NLR = neutrophil-to-lymphocyte ratio; FAR = fibrinogen-to-albumin ratio; IVT = intravenous thrombolysis; EVT = endovascular thrombectomy.

Limitations of Current Evidence

The literature on NLR, FAR, and especially the combined NLR–FAR index has important limitations.

 Predominance of retrospective single-center studies

Most studies are retrospective and single-center, increasing risk of selection bias, incomplete adjustment, and limited generalizability.

 Heterogeneity in biomarker timing

Admission, pre-IVT, post-IVT, pre-EVT, post-EVT, and delayed measurements are often pooled conceptually despite differing biological meanings.

 Inconsistent cut-offs

Thresholds vary widely across studies, limiting bedside standardization.

 Residual confounding

NLR and FAR are influenced by infection, malignancy, chronic inflammatory disease, liver disease, malnutrition, renal dysfunction, steroid exposure, and systemic stress.

 Variable outcome definitions

Some studies use discharge mRS, others 30-day or 90-day mRS, and definitions of poor outcome vary (mRS ≥2, ≥3, or ≥4).

 Limited mechanistic correlation

Few studies integrate biomarker data with imaging endpoints such as infarct volume growth, BBB permeability, collateral status, or reperfusion grades.

 Sparse direct evidence for NLR–FAR

This is the most important limitation. Direct evidence for the combined NLR–FAR index remains very limited within the strict 2015–2025 window. Therefore, strong clinical claims are premature.

 Future Directions

To move the field from association to application, several research priorities are essential.

 Prospective multicenter validation

Large, multicenter prospective cohorts across diverse populations are needed to validate NLR, FAR, and especially NLR–FAR.

 Standardization of the combined index

A consensus definition is needed, including:

•              exact formula,

•              unit harmonization for fibrinogen and albumin,

•              preferred timing (admission vs post-reperfusion), and

•              handling of dynamic serial values.

 Incremental predictive value

Future studies should evaluate whether NLR–FAR adds predictive value beyond established models including:

•              age,

•              NIHSS,

•              ASPECTS,

•              onset-to-treatment time,

•              recanalization grade,

•              collateral status, and

•              glucose.

 This should include AUC, calibration, net reclassification improvement (NRI), and decision-curve analysis.

 Dynamic biomarker trajectories

Single time-point values may underperform compared with serial trends. Trajectory-based models may better capture reperfusion injury and post-stroke complications.

 Integration with imaging and omics

Combining NLR–FAR with perfusion imaging, clot imaging, radiomics, endothelial markers, and NET-related biomarkers could produce more biologically precise risk models.

 Interventional relevance

An important but unanswered question is whether high NLR/FAR identifies patients who may benefit from targeted anti-inflammatory or antithromboinflammatory strategies. Biomarkers are most clinically meaningful when they inform treatment selection.

 Validation in special subgroups

Further work is needed in:

•              IVT-only patients,

•              EVT-only patients,

•              large vessel occlusion,

•              posterior circulation stroke,

•              cardioembolic stroke,

•              elderly/frail patients, and

•              low-resource settings.

The NLR–FAR index represents a conceptually strong and clinically attractive attempt to capture the thromboinflammatory biology of acute ischemic stroke using routine laboratory data. The biological rationale is compelling: NLR reflects innate immune activation and adaptive immune suppression, whereas FAR integrates hypercoagulability, acute-phase inflammation, and diminished physiological reserve. Together, these markers align closely with modern understandings of AIS as a dynamic neurovascular and systemic inflammatory syndrome.

 The current evidence base, however, is asymmetric. NLR is supported by multiple post-2015 cohort studies, systematic reviews, and meta-analyses demonstrating associations with stroke severity, poor functional outcome, hemorrhagic transformation, and mortality—particularly in reperfusion-treated patients. FAR has increasingly promising evidence linking it to poor 3-month outcomes, hemorrhagic transformation after thrombolysis, and adverse outcomes after thrombectomy, but the evidence remains newer and less mature. By contrast, the combined NLR–FAR index remains an emerging research construct with insufficient direct validation within the 2015–2025 evidence window.

 Accordingly, the most scientifically defensible conclusion is that NLR and FAR are useful adjunctive prognostic biomarkers in AIS, whereas the NLR–FAR index should currently be regarded as a promising but preliminary composite marker. It should not yet be used as a standalone clinical decision instrument. Its future value will depend on prospective multicenter validation, standardization of calculation methods, demonstration of incremental predictive utility beyond established clinical-imaging models, and integration into practical risk stratification pathways.

 If these steps are achieved, the NLR–FAR index may evolve into a scalable, low-cost, globally accessible biomarker tool capable of improving individualized prognostication and potentially guiding precision stroke care.

 Abbreviations

AIS – Acute ischemic stroke

AUC – Area under the curve

BBB – Blood–brain barrier

CAR – C-reactive protein-to-albumin ratio

CI – Confidence interval

CRP – C-reactive protein

EVT – Endovascular thrombectomy

FAR – Fibrinogen-to-albumin ratio

HT – Hemorrhagic transformation

IVT – Intravenous thrombolysis

LMR – Lymphocyte-to-monocyte ratio

MMP-9 – Matrix metalloproteinase-9

mRS – Modified Rankin Scale

NETs – Neutrophil extracellular traps

NLR – Neutrophil-to-lymphocyte ratio

NIHSS – National Institutes of Health Stroke Scale

NRI – Net reclassification improvement

OR – Odds ratio

PLR – Platelet-to-lymphocyte ratio

ROS – Reactive oxygen species

sICH – Symptomatic intracranial hemorrhage

SII – Systemic immune-inflammation index.

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