Role of Blood Biomarkers in Differentiating Ischemic Stroke and Intracerebral Hemorrhage

Bhatia, Rohit; Warrier, Anand R; Sreenivas, Vishnubhatla; Bali, Prerna; Sisodia, Pranjal; Gupta, Anvita; Singh, Nishita; Srivastava, M V Padma; Prasad, Kameshwar

doi:10.4103/0028-3886.293467

Cited by 15 publications

(11 citation statements)

References 15 publications

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“…From a clinical point of view, until now no single biomarker identified in the context of stroke is suitable to certainly distinguish IS from ICH (21)(22)(23)(24)128). The most promising results so far have been published for GFAP.…”

Section: Discussionmentioning

confidence: 99%

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Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

et al. 2021

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Background: A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in patients with stroke. However, in resource-limited settings brain imaging, which is the current diagnostic gold standard for this purpose, is not always available in time. Hence, an easily accessible and broadly applicable blood biomarker-based diagnostic test differing stroke subtypes would be desirable. Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH.Material and Methods: Plasma samples from patients with IS and ICH were drawn during hospitalization and were analyzed by using liquid chromatography/mass spectrometry. Proteins were identified using the human reference proteome database UniProtKB, and label-free quantification (LFQ) data were further analyzed using bioinformatic tools.Results: Plasma specimens of three patients with IS and four patients with ICH with a median National Institute of Health Stroke Scale (NIHSS) of 12 [interquartile range (IQR) 10.5–18.5] as well as serum samples from two healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2 (CPN2), Coagulation factor XII (FXII), Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonic anhydrase 1, Fibulin-1, and Granulins.Discussion: In this exploratory proteomics-based pilot study, nine candidate biomarkers for differentiation of IS and ICH were identified. The proteins belong to the immune system, the coagulation cascade, and the apoptosis system, respectively. Further investigations in larger cohorts of patients with stroke using additional biochemical analysis methods, such as ELISA or Western Blotting are now necessary to validate these markers, and to characterize diagnostic accuracy with regard to the development of a point-of-care-system for use in resource-limited areas.

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Section: Discussionmentioning

confidence: 99%

“…However, it reliably distinguishes ICH from IS only within 6 h of symptom onset. Its potential use has been demonstrated in an Indian trial, too (16)(17)(18)(19)(20)(21). On the other side, comparable markers of IS have not been identified so far (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

et al. 2021

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“…Similar to other retrospective analyses, the present study is prone to recall bias (e.g., comorbidities may not be complete) such that an unidentified risk factor may be related to risk of ICH recurrence. Other risk factors as described above and biomarkers of ICH in the general populations, such as D‐dimer, soluble CD163, or troponin were not collected. Whether these risk factors are also risk factors in the leukemia population is presently unknown.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes and transfusion management following intracranial hemorrhage in patients with acute leukemia

et al. 2019

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BACKGROUND There is little evidence to guide management of patients with acute leukemia and intracranial hemorrhage (ICH). Predictors of long‐term outcome following ICH are unknown. STUDY DESIGN AND METHODS This study included adult patients with acute leukemia and ICH over an 8‐year period. The primary outcome was data regarding 90‐day mortality. Secondary outcomes included data related to the proportion of patients receiving post‐remission therapy and predictors of 90‐day mortality. RESULTS ICH occurred in 101 patients; 12 patients died within 72 hours. For the 89 others, 90‐day mortality was 40%. Of 43 patients who received induction, 30 achieved remission and 26 received post‐remission therapy. Older age (p = 0.03) and higher white count (p = 0.02) at the time of ICH were predictive of inferior survival. During 90‐day follow‐up, median platelet count was 37 x 109/L (0‐1526 x 109/L). Lower platelet count during follow‐up was predictive of 90‐day mortality (p = <0.01). Twenty‐one percent of platelet transfusions were provided when the platelet count was less than 10 x 109/L, 54% between 10 and 29 x 109/L, and 25% greater than 30 x 109/L. New or progressive ICH occurred in 23 patients. There was no difference in the median platelet transfusion trigger between patients who had new or progressive ICH and those who did not. CONCLUSION In patients with acute leukemia, survival following ICH is poor. Older age and higher white count is associated with increased mortality, perhaps reflecting higher risk disease. Following ICH in acute leukemia platelet transfusions do not appear to alter the risk of progressive bleeding or mortality.

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“…The related research dates back to 1996 ( Rubattu et al, 1996 ). The scientific community has increasing interest in this area from 2010 ( García-Berrocoso et al, 2010 ; Kim et al, 2010 ; Quan et al, 2010 ) to 2020 ( Bhatia et al, 2020 ; Harpaz et al, 2020 ; Hotsuki et al, 2020 ; Khan and Kamal, 2020 ; Medranda et al, 2020 ; Rubattu et al, 2020 ; Shirotani et al, 2020 ; Tonomura et al, 2020 ; Wang et al, 2020 ; Watson et al, 2020 ; Yang et al, 2020 ; Zhao et al, 2020b ). Several studies explore and identify variable degrees of correlation in different types of stroke.…”

Section: Introductionmentioning

confidence: 99%

Circulating N-Terminal Probrain Natriuretic Peptide Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study

et al. 2022

Front. Genet.

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Mendelian randomization was used to evaluate the potential causal association between N-terminal probrain natriuretic peptide (NT-proBNP) and ischemic stroke based on summary statistics data from large-scale genome-wide association studies. Three single-nucleotide polymorphisms (SNPs) rs198389, rs13107325, and rs11105306 associated with NT-proBNP levels found in large general populations and in patients with acute heart disease were used as instrumental variables. The results of genetic association analysis of each single SNP show that there is no significant association between NT-proBNP levels and ischemic stroke or its subtypes, whereas rs198389 alone has a suggestive association with large-artery atherosclerosis stroke. The MR analysis of three SNPs shows that NT-proBNP levels may reduce the risk of small-vessel occlusion stroke suggestively. This genetic analysis provides insights into the pathophysiology and treatment of ischemic stroke.

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Role of Blood Biomarkers in Differentiating Ischemic Stroke and Intracerebral Hemorrhage

Cited by 15 publications

References 15 publications

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

Clinical outcomes and transfusion management following intracranial hemorrhage in patients with acute leukemia

Circulating N-Terminal Probrain Natriuretic Peptide Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study

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