Low hemoglobin, albumin, lymphocyte, and platelet score increases symptomatic intracranial hemorrhage risk in thrombectomy patients

Abstract

Background:

The HALP index, a composite biomarker integrating hemoglobin, albumin, lymphocyte, and platelet parameters, reflects both immunological competence and nutritional status. We therefore conducted this retrospective analysis to assess the correlation between HALP score and the risk symptomatic intracranial hemorrhage (sICH) risk in patients receiving mechanical thrombectomy (MT).

Methods:

This retrospective study included patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent MT between October 2019 and July 2024. The HALP index was calculated based on admission laboratory parameters. The sICH was diagnosed according to Heidelberg Bleeding Classification criteria within 72 h post-procedure. Multivariate logistic regression analysis was performed to identify independent association between pretreatment HALP score and sICH risk after adjusting for covariates.

Results:

A total of 735 patients (mean age, 71.3 ± 10.9 years; 423 male) were enrolled in this study. sICH was diagnosed in 82 patients (11.2%) during hospitalization. After adjusting for demographic characteristics and other covariates, multivariate logistic regression analysis revealed that a low HALP index was significantly associated with an elevated risk of sICH (odds ratio: 1.058, 95% confidence interval: 1.024–1.094, p = 0.001). findings were obtained when the HALP score was analyzed as a categorical variable. Additionally, the restricted cubic spline analysis confirmed a linear inverse relationship between the HALP index and the risk of sICH following MT (p = 0.551 for non-linearity).

Conclusion:

Our data confirmed a significant inverse correlation between the HALP score and the sICH risk in patients treated with MT. This suggests that the HALP score may serve as a valuable tool for monitoring and managing sICH risk in ischemic stroke patients following reperfusion therapy.

1 Introduction

Ischemic stroke is a leading cause of disability and mortality worldwide, imposing substantial medical and financial burdens globally (1, 2). Numerous randomized controlled trials have established that mechanical thrombectomy (MT) is effective for ischemic stroke patients with large vessel occlusion in the anterior circulation (3). Symptomatic intracranial hemorrhage (sICH) is a serious complication following reperfusion therapy, strongly associated with neurological deterioration and poor functional outcomes (4, 5). Therefore, early and accurate prediction of sICH is essential for optimizing functional recovery after MT.

Stroke outcomes are influenced by a multitude of factors, including genetic predisposition, modifiable lifestyle choices, dietary patterns, and cardiometabolic conditions. Inflammatory processes play a significant role in these mechanisms. Extensive research has shown that lymphocytes can alleviate neuronal damage by regulating inflammatory responses and act as key immunomodulators during acute ischemic stroke (6). Beyond their role in thrombosis, platelets also contribute to the inflammatory response triggered by ischemic stroke, primarily through interactions between platelet receptors and endothelial or immune cells (7). The Thrombolysis in Stroke Patients registry, which included 7,533 stroke patients treated with intravenous thrombolysis, demonstrated that a lower platelet count was significantly associated with an increased risk of sICH, while a higher platelet count correlated with a greater risk of mortality (8). Additionally, malnutrition is linked to stroke-related complications. Previous studies have indicated that low hemoglobin levels can lead to cerebral hypoxia, mitochondrial dysfunction, and neuronal damage (9). Deficiencies in serum albumin have been associated with poorer 90-day outcomes in patients with large artery occlusive stroke following MT (10), partly due to reduced antioxidant capacity after ischemic injury. Recently, the HALP (hemoglobin, albumin, lymphocyte, and platelet) index has emerged as a validated marker for evaluating systemic inflammation and nutritional status (11). The HALP index has gained recognition as a novel predictor of clinical outcomes in various cancers (12) and has also been shown to predict stroke recurrence and cognitive impairment in ischemic stroke patients (13, 14). However, the relationship between the HALP score and sICH in patients undergoing thrombectomy remains unclear.

Therefore, we conducted this study to evaluate the association between the HALP index and the risk of sICH in ischemic stroke patients following MT.

2 Materials and methods

2.1 Subjects and study design

We retrospectively analyzed acute ischemic stroke patients who underwent MT at Nanjing First Hospital between October 2019 and July 2024 for large vessel occlusion in the anterior circulation. The inclusion criteria were as follows: (1) age 18 years or older; (2) presence of anterior circulation large vessel occlusion (internal carotid artery or middle cerebral artery M1/M2 segments); and (3) availability of data necessary for calculating the HALP score. To ensure the homogeneity of the study population, we excluded patients with malignant tumors or hematological disorders. All procedures performed in studies involving human participants were reviewed and approved by the Ethics Committee of Nanjing First Hospital. This study complies with the Declaration of Helsinki. Due to its retrospective nature; patient consent was waived by the Ethics Committee of Nanjing First Hospital. Patient data confidentiality was maintained in Nanjing First Hospital.

2.2 Baseline variables assessment

We collected data on demographic characteristics, vascular risk factors, imaging findings, procedural details, and laboratory results. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate baseline neurological deficits (15). The Alberta Stroke Program Early CT Score (ASPECTS) was applied to measure pre-treatment infarct volume (16). Stroke subtypes were classified according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) criteria (17). Collateral circulation was evaluated using digital subtraction angiography and graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale, with grades 0–1 indicating poor collateral circulation and grades 2–4 representing moderate to excellent collateral circulation (18). Successful recanalization was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b–3 (19).

2.3 Measurement of HALP score

Fasting whole blood samples were collected within 24 h of admission and systematically processed for all laboratory analyses. The HALP index was calculated using the following formula: hemoglobin levels (g/L) × albumin levels (g/L) × lymphocyte counts (/L) / platelet counts (/L) (20).

2.4 Definition of sICH

sICH was diagnosed based on the Heidelberg Bleeding Classification within 72 h post-MT (21).

2.5 Statistical analysis

Quantitative variables were expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]), depending on the distribution normality, while categorical variables were presented as frequencies (percentages). Continuous variables were compared using the Student’s t-test or Mann–Whitney U test, and categorical variables were analyzed using the chi-square test or Fisher’s exact test. Binary logistic regression analysis was conducted to assess the association between the HALP score and the likelihood of sICH. Model 1 was adjusted for age and sex; Model 2 was further adjusted for baseline ASPECTS and poor collateral circulation. In model 3, additional adjustments were made for demographic characteristics and variables with a p value <0.1 in the univariate analysis, including baseline NIHSS score, baseline ASPECTS, prior intravenous thrombolysis, poor collateral status, fasting blood glucose, hemoglobin, and lymphocyte count. Variance Inflation Factor (VIF) was used for evaluating multicollinearity between HALP and its components. Furthermore, the pattern and magnitude of the relationship between the HALP index and sICH risk were evaluated using restricted cubic splines with three knots (at the 5th, 50th, and 95th percentiles), adjusted for the covariates included in Model 3. We also used the receiver operating characteristic (ROC) curve analysis to detect the discriminative ability of the HALP index in predicting sICH.

All statistical analyses were performed using IBM SPSS Statistics (version 25.0) and R software (version 4.3.1). A two-tailed p value <0.05 was considered statistically significant in this study.

3 Results

3.1 Baseline characteristics

This study enrolled 735 consecutive ischemic stroke patients, with 57.6% being male and a mean age of 71.3 ± 10.9 years. Among them, 265 patients (36.1%) received intravenous thrombolysis prior to endovascular treatment (EVT). Poor collateral circulation was observed in 328 patients (44.6%), and successful reperfusion was achieved in 91.7% of cases. Table 1 provides detailed clinical data stratified by HALP quartiles. Significant differences were observed across HALP quartiles in baseline NIHSS scores, poor collateral circulation, and fasting blood glucose levels. However, demographic characteristics and vascular risk factors showed no significant differences among the groups.

3.2 Risk factors of sICH after MT

The mean HALP score among the study participants was 32.2. Based on the Heidelberg Bleeding Classification, 82 patients (11.2%) were diagnosed with sICH. Table 2 summarizes the age, sex, baseline clinical data, and laboratory findings of patients with and without sICH. Univariate analysis revealed that patients with sICH had higher NIHSS scores (median: 15.0 vs. 13.0; p = 0.044) and lower baseline ASPECTS scores (median: 8.0 vs. 9.0; p = 0.003) compared to those without sICH. Prior intravenous thrombolysis (46.3% vs. 34.8%; p = 0.040) and poor collateral circulation (62.2% vs. 42.4%; p = 0.001) were more common in patients with sICH than in those without. Additionally, patients with sICH exhibited higher fasting blood glucose levels (mean: 8.2 ± 2.35 mmol/L vs. 7.07 ± 2.41 mmol/L; p = 0.001) and lower hemoglobin concentrations (1.1 ± 0.4 g/L vs. 1.2 ± 0.6 g/L; p = 0.046) compared to those without sICH. The HALP index was significantly lower in patients with sICH than in those without (mean: 26.2 ± 13.4 vs. 32.8 ± 19.7; p = 0.001).

3.3 Associations between HALP index and sICH risk

After adjusting for covariates, multivariate logistic regression analysis revealed that a higher HALP index was significantly associated with a reduced risk of sICH (odd ratios, 1.058; 95% confidence interval, 1.024–1.094, p = 0.001). These findings were further supported when the HALP index was analyzed as a categorical variable (1st quartile vs. 4th quartile of HAPL score, odd ratios, 7.342; 95% confidence interval, 2.962–18.200, p = 0.001; Table 3). Additionally, restricted cubic spline analysis confirmed a linear inverse relationship between the HALP index and sICH risk (p = 0.551 for non-linearity; p = 0.001 for linearity; Figure 1). In the ROC analysis, the area under the ROC curve values of the HALP index were 0.709 (95% CI: 0.657–0.761, p = 0.027; Figure 2). Also, the predictive ability of the HALP index is superior to baseline NIHSS score (AUC = 0.666), baseline glucose levels (AUC = 0.694), poor collateral status (AUC = 0.566), and prior IVT treatment (AUC = 0.512).

Figure 1

Figure 2

4 Discussion

This study identified the HALP index as an independent predictor of sICH in patients with large artery occlusive stroke undergoing MT. This association remained significant even after adjusting for potential confounders, suggesting that the HALP index could serve as a modifiable risk factor for thrombectomy patients.

The HALP index, calculated from hemoglobin levels, albumin levels, lymphocyte counts, and platelet counts, reflects the interplay between inflammation and nutritional status. Previous clinical studies have demonstrated that a lower HALP index is strongly associated with an increased risk of cardiovascular diseases and overall mortality (22, 23). The HALP index also demonstrates a significant correlation with the risk of post-stroke cognitive impairment (24) and poor outcomes (13). Even though the underlying mechanisms connecting the HALP score and sICH remain unclear, the components of the index might shed light on these observations. Firstly, systemic inflammation is thought to be associated with increased endothelial dysfunction and the impairment of the blood—brain barrier following cerebral ischemia (25). Moreover, highly reactive platelets are indicative of a severe pro-inflammatory state (26, 27). Additionally, platelets can interact with platelet-binding T lymphocytes to produce cytokines, interferons, and chemokines. As a result, this interaction modifies the blood—brain barrier after a stroke (28). Secondly, lymphocytes assume pivotal regulatory functions in the inflammatory process subsequent to ischemic stroke (29). A decrease in lymphocyte levels has been associated with larger infarct volumes and higher NIHSS scores (30). Significantly, both of these factors are independent predictors of sICH (31). Thirdly, hypoalbuminemia contributes to the occurrence of sICH. It does so by intensifying the inflammatory response and oxidative stress (32), stimulating platelet aggregation (33), and enhancing cytokine adhesion within the postcapillary microcirculation (34). Finally, robust evidence demonstrates that reduced hemoglobin levels can give rise to brain hypoxia, mitochondrial dysfunction, and neuronal damage, thus increasing the risk of hemorrhage (9). Additional research is essential to thoroughly clarify the role of the HALP score in predicting the risk of sICH after reperfusion therapy.

We demonstrated that 82 patients (11.2%) experienced sICH during hospitalization. This percentage is slightly higher than the rates reported in several randomized controlled trials (3), as well as those observed in the MR CLEAN Registry (5.8%) (35) and the NASA Registry (9.9%) (36). The data in these registries were predominantly obtained from white populations. This disparity might be attributed to the higher prevalence of cerebral atherosclerosis in the Asian population. Intracranial atherosclerotic occlusion is often more difficult to recanalize successfully compared to cardioembolic occlusion, since the former is frequently associated with significant stenosis. Notably, in this study, a correlation was found between sICH and the number of passes made with the retriever. Repeated use of the thrombectomy device for atherosclerotic occlusion may lead to vascular endothelial damage and disrupt the blood–brain barrier, both of which are linked to an increased risk of sICH (37). However, differences in study methods and the definitions of sICH could potentially explain this discrepancy.

Several limitations in our study need to be acknowledged. First, there is an absence of clinical data on whether patients have pre-existing factors affecting the calculation of the HALP, such as a history of infection and medications. Secondly, given the nature of our study design, this research was unable to establish a causal relationship between HALP and the risk of sICH. Thirdly, the study failed to document whether the patients had been taking medications capable of influencing HALP scores prior to the commencement of the study. Examples of such medications include anti—platelet drugs and iron supplements. Finally, this research was executed at a solitary hospital in China and encompassed a particular cohort of cerebral infarction patients. This fact may potentially restrict the applicability and generalizability of the study findings. Consequently, multicenter studies involving large and diverse sample sizes are imperative to validate and strengthen our research findings.

In summary, this study clearly demonstrated that low HALP index was significantly associated with the risk of sICH in patients suffering from large artery occlusive stroke subsequent to MT therapy. The HALP score holds the potential to enhance the early and precisely-targeted treatment of stroke for these high-risk patients. Further research is essential to evaluate the potential effectiveness of dietary interventions and anti-inflammatory therapies in preventing sICH following MT treatment.

References

• 1.

  Wang Y Li Z Gu H Zhai Y Zhou Q Jiang Y et al . China stroke statistics: an update on the 2019 report from the National Center for healthcare quality Management in Neurological Diseases, China National Clinical Research Center for neurological diseases, the Chinese Stroke Association, National Center for chronic and non-communicable disease control and prevention, Chinese Center for Disease Control and Prevention and institute for global neuroscience and stroke collaborations. Stroke Vasc Neurol. (2022) 7:415–50. doi: 10.1136/svn-2021-001374

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 2.

  GBD 2019 Stroke Collaborators . Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet Neurol. (2021) 20:795–820. doi: 10.1016/S1474-4422(21)00252-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 3.

  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) 387:1723–31. doi: 10.1016/S0140-6736(16)00163-X

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 4.

  Zhang M Xing P Tang J Shi L Yang P Zhang Y et al . Predictors and outcome of early neurological deterioration after endovascular thrombectomy: a secondary analysis of the DIRECT-MT trial. J Neurointerv Surg. (2023) 15:e9–e16. doi: 10.1136/neurintsurg-2022-018976

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 5.

  Hao Y Yang D Wang H Zi W Zhang M Geng Y et al . Predictors for symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke. Stroke. (2017) 48:1203–9. doi: 10.1161/STROKEAHA.116.016368

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 6.

  Ren X Akiyoshi K Dziennis S Vandenbark A Herson P Hurn P et al . Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke. J Neurosci. (2011) 31:8556–63. doi: 10.1523/JNEUROSCI.1623-11.2011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 7.

  Cui J Li H Chen Z Dong T He X Wei Y et al . Thrombo-inflammation and immunological response in ischemic stroke: focusing on platelet-Tregs interaction. Front Cell Neurosci. (2022) 16:955385. doi: 10.3389/fncel.2022.955385

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 8.

  Gensicke H Al Sultan AS Strbian D Hametner C Zinkstok SM Moulin S et al . Intravenous thrombolysis and platelet count. Neurology. (2018) 90:e690–7. doi: 10.1212/WNL.0000000000004982

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 9.

  Wang X Mori T Sumii T Lo E . Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: caspase activation and oxidative stress. Stroke. (2002) 33:1882–8. doi: 10.1161/01.str.0000020121.41527.5d

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 10.

  Gao J Zhao Y Du M Guo H Wan T Wu M et al . Serum albumin levels and clinical outcomes among ischemic stroke patients treated with endovascular Thrombectomy. Neuropsychiatr Dis Treat. (2021) 17:401–11. doi: 10.2147/NDT.S293771

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 11.

  Liu X Qiu Z Ndhlovu E Wan Y Sun H Wang S et al . Establishing and externally validating a hemoglobin, albumin, lymphocyte, and platelet (HALP) score-based nomogram for predicting early recurrence in BCLC stage 0/a hepatocellular carcinoma patients after radical liver resection: a multi-center study. J Hepatocell Carcinoma. (2024) 11:1127–41. doi: 10.2147/JHC.S465670

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 12.

  Guo Y Shi D Zhang J Mao S Wang L Zhang W et al . The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a novel significant prognostic factor for patients with metastatic prostate Cancer undergoing Cytoreductive radical prostatectomy. J Cancer. (2019) 10:81–91. doi: 10.7150/jca.27210

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 13.

  Tian M Li Y Wang X Tian X Pei L Wang X et al . The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is associated with poor outcome of acute ischemic stroke. Front Neurol. (2021) 11:610318. doi: 10.3389/fneur.2020.610318

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 14.

  Xu M Chen L Hu Y Wu J Wu Z Yang S et al . The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is associated with early-onset post-stroke cognitive impairment. Neurol Sci. (2023) 44:237–45. doi: 10.1007/s10072-022-06414-z

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 15.

  Sucharew H Khoury J Moomaw CJ Alwell K Kissela BM Belagaje S et al . Profiles of the National Institutes of Health stroke scale items as a predictor of patient outcome. Stroke. (2013) 44:2182–7. doi: 10.1161/STROKEAHA.113.001255

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 16.

  Barber PA Demchuk AM Zhang J Buchan AM . Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS study group. Alberta stroke Programme early CT score. Lancet. (2000) 355:1670–4. doi: 10.1016/S0140-6736(00)02237-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 17.

  Adams HP Jr Bendixen BH Kappelle LJ Biller J Love BB Gordon DL et al . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. (1993) 24:35–41. doi: 10.1161/01.STR.24.1.35

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 18.

  Carvalho A Rocha M Rodrigues M Gregório T Costa H Cunha A et al . Time to reset the definition of successful revascularization in endovascular treatment of acute ischemic stroke. Cerebrovasc Dis. (2018) 46:40–5. doi: 10.1159/000491553

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 19.

  Zhang X Peng M Feng C Wang H Gong P Jiang T et al . Nomogram predicting early neurological improvement in ischaemic stroke patients treated with endovascular thrombectomy. Eur J Neurol. (2021) 28:152–60. doi: 10.1111/ene.14510

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 20.

  Chen XL Xue L Wang W Chen HN Zhang WH Liu K et al . Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study. Oncotarget. (2015) 6:41370–82. doi: 10.18632/oncotarget.5629

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 21.

  von Kummer R Broderick JP Campbell BC Demchuk A Goyal M Hill MD et al . The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. (2015) 46:2981–6. doi: 10.1161/STROKEAHA.115.010049

  • CrossRef
  • Google Scholar

• 22.

  Pan H Lin S . Association of hemoglobin, albumin, lymphocyte, and platelet score with risk of cerebrovascular, cardiovascular, and all-cause mortality in the general population: results from the NHANES 1999-2018. Front Endocrinol (Lausanne). (2023) 14:1173399. doi: 10.3389/fendo.2023.1173399

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 23.

  Zheng Y Huang Y Li H . Hemoglobin albumin lymphocyte and platelet score and all-cause mortality in coronary heart disease: a retrospective cohort study of NHANES database. Front Cardiovasc Med. (2023) 10:1241217. doi: 10.3389/fcvm.2023.1241217

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 24.

  Zuo L Dong Y Liao X Hu Y Pan Y Yan H et al . Low HALP (hemoglobin, albumin, lymphocyte, and platelet) score increases the risk of post-stroke cognitive impairment: a multicenter cohort study. Clin Interv Aging. (2024) 19:81–92. doi: 10.2147/CIA.S432885

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 25.

  Evans LE Taylor JL Smith CJ Pritchard HAT Greenstein AS Allan SM . Cardiovascular comorbidities, inflammation, and cerebral small vessel disease. Cardiovasc Res. (2021) 117:2575–88. doi: 10.1093/cvr/cvab284

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 26.

  Reininger AJ Bernlochner I Penz SM Ravanat C Smethurst P Farndale RW et al . A 2-step mechanism of arterial thrombus formation induced by human atherosclerotic plaques. J Am Coll Cardiol. (2010) 55:1147–58. doi: 10.1016/j.jacc.2009.11.051

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 27.

  Viallard JF Solanilla A Gauthier B Contin C Déchanet J Grosset C et al . Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis. Blood. (2002) 99:2612–4. doi: 10.1182/blood.v99.7.2612

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 28.

  Salas-Perdomo A Miró-Mur F Urra X Justicia C Gallizioli M Zhao Y et al . T cells prevent hemorrhagic transformation in ischemic stroke by P-selectin binding. Arterioscler Thromb Vasc Biol. (2018) 38:1761–71. doi: 10.1161/ATVBAHA.118.311284

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 29.

  Baird AE . The forgotten lymphocyte: immunity and stroke. Circulation. (2006) 113:2035–6. doi: 10.1161/CIRCULATIONAHA.105.620732

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 30.

  Kim J Song TJ Park JH Lee HS Nam CM Nam HS et al . Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction. Atherosclerosis. (2012) 222:464–7. doi: 10.1016/j.atherosclerosis.2012.02.042

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 31.

  Dong S Yu C Wu Q Xia H Xu J Gong K et al . Predictors of symptomatic intracranial hemorrhage after endovascular Thrombectomy in acute ischemic stroke: a systematic review and Meta-analysis. Cerebrovasc Dis. (2023) 52:363–75. doi: 10.1159/000527193

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 32.

  Ishizaka N Ishizaka Y Nagai R Toda E Hashimoto H Yamakado M . Association between serum albumin, carotid atherosclerosis, and metabolic syndrome in Japanese individuals. Atherosclerosis. (2007) 193:373–9. doi: 10.1016/j.atherosclerosis.2006.06.031

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 33.

  Maalej N Albrecht R Loscalzo J Folts J . The potent platelet inhibitory effects of S-nitrosated albumin coating of artificial surfaces. J Am Coll Cardiol. (1999) 33:1408–14. doi: 10.1016/S0735-1097(98)00687-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 34.

  Belayev L Pinard E Nallet H Seylaz J Liu Y Riyamongkol P et al . Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses. Stroke. (2002) 33:1077–84. doi: 10.1161/hs0402.105555

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 35.

  van de Graaf RA Chalos V van Es ACGM Emmer BJ Lycklama À Nijeholt GJ van der Worp HB et al . Periprocedural intravenous heparin during endovascular treatment for ischemic stroke: results from the MR CLEAN registry. Stroke. (2019) 50:2147–55. doi: 10.1161/STROKEAHA.119.025329

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 36.

  Zaidat O Castonguay A Gupta R Sun C Martin C Holloway W et al . North American solitaire stent retriever acute stroke registry: post-marketing revascularization and clinical outcome results. J Neurointerv Surg. (2014) 6:584–8. doi: 10.1136/neurintsurg-2013-010895

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 37.

  Leigh R Christensen S Campbell B Marks M Albers G Lansberg M et al . Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology. (2016) 87:263–9. doi: 10.1212/WNL.0000000000002862

  • Pubmed Abstract
  • CrossRef
  • Google Scholar