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Intensive Care Medicine Apr 2016Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients.
METHODS
We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language.
RESULTS
We included 30 RCTs with a total of 3933 participants. The majority of included trials were at high risk of bias. Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality (RR 0.95, 95% CI 0.88-1.03, I (2) = 0%, fixed-effect model, 29 trials, 3882 participants). Among those with severe sepsis and disseminated intravascular coagulation (DIC), AT III showed no impact on mortality (RR 0.95, 95% Cl 0.88-1.03, I (2) = 0%, fixed-effect model, 12 trials, 2858 participants). We carried out multiple subgroup and sensitivity analyses to assess the benefits and harms of AT III and to examine the impact of risk of bias. AT III significantly increased bleeding events (RR 1.58, 95% CI 1.35-1.84, I (2) = 0%, fixed-effect model, 11 trials, 3019 participants). However, for all other outcome measures and analyses, the results did not reach statistical significance.
CONCLUSIONS
There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact on mortality, but increased the risk of bleeding.
Topics: Antithrombin III; Antithrombins; Critical Illness; Disseminated Intravascular Coagulation; Humans; Randomized Controlled Trials as Topic; Sepsis
PubMed: 26862016
DOI: 10.1007/s00134-016-4225-7 -
Pharmacological Research Oct 2017Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII)... (Meta-Analysis)
Meta-Analysis Review
Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29, p=0.094) or ≥12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone.
Topics: Antithrombin III; Controlled Clinical Trials as Topic; Estrogen Receptor Modulators; Fibrinogen; Humans; Norpregnenes
PubMed: 28760491
DOI: 10.1016/j.phrs.2017.07.024 -
Systematic Reviews Feb 2023Thrombin-antithrombin complex (TAT) is a prethrombotic marker, and its application in ischemic stroke is still uncertain. The purpose of this systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Thrombin-antithrombin complex (TAT) is a prethrombotic marker, and its application in ischemic stroke is still uncertain. The purpose of this systematic review and meta-analysis is to evaluate the relationship between plasma TAT and ischemic stroke base on the current evidence.
METHODS
A systematic literature search was conducted for searching the relative studies that investigated the association of TAT and ischemic stroke in PubMed, EMBASE, and Cochrane library databases. Mean difference and 95% confidence interval as the effect sizes were synthesized by random effects model in Review Manager (RevMan) Version 5.4. The heterogeneity was investigated using the chi-square test and the possible sources of heterogeneity were explored by sensitivity analysis and meta-regression. The publication bias was estimated by Egger's tests.
RESULTS
A total of 12 eligible studies were included involving 1431 stroke cases and 532 healthy controls, of which six studies were eventually included in the meta-analysis. Plasma TAT in patients with ischemic stroke was significantly higher than that in healthy controls (MD 5.31, 95% CI = 4.12-6.51, P < 0.0001, I = 97.8%). There is a difference of TAT level in the same period among cardioembolic, lacunar, and atherothrombotic stroke (all P < 0.0001), in which the cardioembolic stroke with the highest level. Meanwhile, it is significant of TAT levels among various phases of cardioembolic stroke and the acute phase are markedly elevated (MD 7.75, 95CI%, 6.07-9.43, P < 0.001). However, no difference was found in the atherothrombotic (P = 0.13) and lacunar stroke (P = 0.34). Besides, the higher TAT level is closely related to the poor prognosis of patients with ischemic stroke, including higher recurrence, mortality, unfavorable recovery (modified Rankin scale > 2), and poor revascularization.
CONCLUSIONS
This study suggested that plasma TAT levels are different in ischemic stroke subtypes, which are closely associated with the progression and might have an effect on the prognosis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD: 42021248787.
Topics: Humans; Brain Ischemia; Embolic Stroke; Ischemic Stroke
PubMed: 36788633
DOI: 10.1186/s13643-023-02174-9 -
Journal of Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
The Cochrane Database of Systematic... Feb 2016Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown. This review was published in 2008 and updated in 2015.
OBJECTIVES
To examine:1. The effect of AT III on mortality in critically ill participants.2. The benefits and harms of AT III.We investigated complications specific and not specific to the trial intervention, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general.
SEARCH METHODS
We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP,), CAB, BIOSIS and CINAHL. We contacted the main authors of trials to ask for any missed, unreported or ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We contacted the investigators and the trial authors in order to retrieve missing data. In this updated review we include trials only published as abstracts.
DATA COLLECTION AND ANALYSIS
Our primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetrics, and paediatrics), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed trial sequential analysis (TSA) to establish the implications for further research.
MAIN RESULTS
We included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I² statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I² statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I² statistic = 0%, fixed-effect model, 20 trials, 967 participants).For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I² statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.Our secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I² statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I² statistic = 28%, random-effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I² statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I² statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was -2.18 (95% Cl -4.36 to -0.00, I² statistic = 0%, fixed-effect model, 3 trials, 102 participants, very low quality of evidence). The incidence of respiratory failure had a RR of 0.93 (95% Cl 0.76 to 1.14, I² statistic = 32%, random-effects model, 6 trials, 2591 participants, moderate quality of evidence). AT III had no statistically significant impact on the duration of mechanical ventilation (MD 2.20 days, 95% Cl -1.21 to 5.60, I² statistic = 0%, fixed-effect model, 3 trials, 190 participants, very low quality of evidence); on the length of stay in the ICU (MD 0.24, 95% Cl -1.34 to 1.83, I² statistic = 0%, fixed-effect model, 7 trials, 376 participants, very low quality of evidence) or on the length of stay in hospital in general (MD 1.10, 95% Cl -7.16 to 9.36), I² statistic = 74%, 4 trials, 202 participants, very low quality of evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support AT III substitution in any category of critically ill participants including the subset of patients with sepsis and DIC. We did not find a statistically significant effect of AT III on mortality, but AT III increased the risk of bleeding events. Subgroup analyses performed according to duration of intervention, length of follow-up, different patient groups, and use of adjuvant heparin did not show differences in the estimates of intervention effects. The majority of included trials were at high risk of bias (GRADE; very low quality of evidence for most of the analyses). Hence a large RCT of AT III is needed, without adjuvant heparin among critically ill patients such as those with severe sepsis and DIC, with prespecified inclusion criteria and good bias protection.
Topics: Anti-Inflammatory Agents; Anticoagulants; Antithrombin III; Critical Illness; Humans; Randomized Controlled Trials as Topic
PubMed: 26858174
DOI: 10.1002/14651858.CD005370.pub3 -
The Canadian Journal of Cardiology Mar 2015Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes in patients with AF. The prognostic value of inflammatory and hemostatic markers in AF has been widely studied; however, the results of previous studies have been inconclusive.
METHODS
We conducted a systematic review and meta-analysis to evaluate the association of inflammatory and hemostatic markers with stroke and thromboembolic events in patients with AF.
RESULTS
A total of 27 studies including 22,176 participants met our inclusion criteria for the systematic review. Our meta-analysis determined that elevated circulating plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) were significantly associated with increased risk of stroke in patients with AF (standardized mean difference [SMD], 0.89; 95% confidence interval [CI], 0.20-1.59 and 1.43; 95% CI, 0.40-2.47, respectively). Higher levels of D-dimer were associated with increased subsequent thromboembolic event risk with a pooled hazard ratio of 2.90 (95% CI, 1.22-6.90) for cohort studies and an SMD of 0.93 (95% CI, 0.36-1.50) for case-control studies. There was also very limited evidence indicating that other biomarkers-such as interleukin-6, von Willebrand factor, P-selectin, and mean platelet volume-could predict adverse outcomes in AF.
CONCLUSIONS
In conclusion, increased circulating PAI-1 and TAT levels were significantly associated with subsequent stroke in patients with AF, and high levels of D-dimer were associated with thromboembolic events in AF. Further epidemiologic studies are needed to accumulate more evidence on the prognostic role of inflammatory and hemostatic markers in AF.
Topics: Anticoagulants; Antifibrinolytic Agents; Antithrombin III; Atrial Fibrillation; Biomarkers; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Mean Platelet Volume; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prognosis; Selectins; Sensitivity and Specificity; Serine Proteinase Inhibitors; Stroke; Thromboembolism; von Willebrand Factor
PubMed: 25746020
DOI: 10.1016/j.cjca.2014.12.002 -
Medical Science Monitor Basic Research Mar 2017BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the... (Meta-Analysis)
Meta-Analysis Review
Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review.
BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusive. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating the association of coagulation activation, fibrinolytic, and endothelial function with occurrence of AF and clinical adverse events. A comprehensive subgroup analysis and meta-regression was performed to explore potential sources of heterogeneity. RESULTS A literature search of major databases retrieved 1703 studies. After screening, a total of 71 studies were identified. Pooled analysis showed the association of coagulation markers (D-dimer (weighted mean difference (WMD) =197.67 and p<0.001), fibrinogen (WMD=0.43 and p<0.001), prothrombin fragment 1-2 (WMD=0.53 and p<0.001), antithrombin III (WMD=23.90 and p=0.004), thrombin-antithrombin (WMD=5.47 and p=0.004)); fibrinolytic markers (tissue-type plasminogen activator (t-PA) (WMD=2.13 and p<0.001), plasminogen activator inhibitor (WMD=11.44 and p<0.001), fibrinopeptide-A (WMD=4.13 and p=0.01)); and endothelial markers (von Willebrand factor (WMD=27.01 and p<0.001) and soluble thrombomodulin (WMD=3.92 and p<0.001)) with AF. CONCLUSIONS The levels of coagulation, fibrinolytic, and endothelial markers have been reported to be significantly higher in AF patients than in SR patients.
Topics: Atrial Fibrillation; Biomarkers; Blood Coagulation Factors; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Stroke; Thromboembolism; Tissue Plasminogen Activator
PubMed: 28360407
DOI: 10.12659/MSMBR.902558 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068 -
Obstetrics and Gynecology Apr 2016To evaluate the risk of pregnancy-associated venous thromboembolism in women with asymptomatic antithrombin deficiency. (Review)
Review
OBJECTIVE
To evaluate the risk of pregnancy-associated venous thromboembolism in women with asymptomatic antithrombin deficiency.
DATA SOURCES
The search was performed on MEDLINE (Ovid and PubMed databases) for the period 1966 to June 2012 and ClinicalTrials.gov as of December 15, 2015.
METHODS OF STUDY SELECTION
A systematic review including randomized controlled trials, cohort studies, and case-control studies was conducted. Selection criteria included objectively diagnosed venous thromboembolism or venous thromboembolism treated with 3 months of anticoagulation before the availability of objective testing. The study population consisted of pregnant women with asymptomatic antithrombin deficiency.
TABULATION, INTEGRATION, AND RESULTS
Seven publications were included in the review. No randomized controlled trials were identified. The best available data consist of three retrospective cohort studies and four case-control studies. Pooled results from case-control studies yielded an estimated odds ratio for venous thromboembolism of 6.09 (95% confidence interval 1.58-23.43). No pooled estimates could be obtained for cohort studies. Data on use of thromboprophylaxis were scarce.
CONCLUSION
Despite the small number of patients included, and the variation in study designs, pooled results from case-control studies show a significant association between asymptomatic antithrombin deficiency and pregnancy-associated venous thromboembolism. Thromboprophylaxis during pregnancy and postpartum should be considered in these women.
Topics: Adult; Antithrombin III Deficiency; Asymptomatic Diseases; Case-Control Studies; Female; Humans; Odds Ratio; Pregnancy; Pregnancy Complications, Cardiovascular; Retrospective Studies; Risk Factors; Venous Thromboembolism
PubMed: 26959206
DOI: 10.1097/AOG.0000000000001347 -
Frontiers in Neurology 2021Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although...
Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although imaging is critical for this process, these biomarkers may provide additional information to distinguish actual stroke from its mimics and monitor patient condition and the effect of potential neuroprotective strategies. For such biomarkers to be effectively scalable to public health in any economic setting, these must be cost-effective and non-invasive. We hypothesized that blood-based combinations (panels) of proteins might be the key to this approach and explored this possibility through a systematic review. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines for systematic review. Initially, the broader search for biomarkers for early stroke diagnosis yielded 704 hits, and five were added manually. We then narrowed the search to combinations (panels) of the protein markers obtained from the blood. Twelve articles dealing with blood-based panels of protein biomarkers for stroke were included in the systematic review. We observed that NR2 peptide (antibody against the NR2 fragment) and glial fibrillary acidic protein (GFAP) are brain-specific markers related to stroke. Von Willebrand factor (vWF), matrix metalloproteinase 9 (MMP-9), and S100β have been widely used as biomarkers, whereas others such as the ischemia-modified albumin (IMA) index, antithrombin III (AT-III), and fibrinogen have not been evaluated in combination. We herein propose the following new combination of biomarkers for future validation: panel 1 (NR2 + GFAP + MMP-9 + vWF + S100β), panel 2 (NR2 + GFAP + MMP-9 + vWF + IMA index), and panel 3 (NR2 + GFAP + AT-III + fibrinogen). More research is needed to validate, identify, and introduce these panels of biomarkers into medical practice for stroke recurrence and diagnosis in a scalable manner. The evidence indicates that the most promising approach is to combine different blood-based proteins to provide diagnostic precision for health interventions. Through our systematic review, we suggest three novel biomarker panels based on the results in the literature and an interpretation based on stroke pathophysiology.
PubMed: 34122297
DOI: 10.3389/fneur.2021.638693