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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 -
Thrombosis Research Aug 2023Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice.
AIMS
This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab.
METHODS
A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation.
RESULTS
Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %-69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %-37.2 %), to enable thrombolysis (range: 2.0 %-27.3 %), dabigatran intoxication without bleeding (range: 3.6 %-7.0 %) or unspecified reasons (range: 0.4 %-18.8 %). Overall, 2.8 % (95%CI 0.5 %-6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %-87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %-100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %-17.9 %) and 2.0 % (95%CI 0.8 %-3.4 %), respectively.
CONCLUSION
Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.
Topics: Humans; Dabigatran; Antithrombins; Antibodies, Monoclonal, Humanized; Hemorrhage; Thromboembolism; Hemostatics
PubMed: 37267671
DOI: 10.1016/j.thromres.2023.05.020 -
Science Progress 2021All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from... (Meta-Analysis)
Meta-Analysis
All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43-1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37-2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73-2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40-1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism
PubMed: 33913387
DOI: 10.1177/00368504211012160 -
BMJ (Clinical Research Ed.) Dec 2007To evaluate the benefits and harms of antithrombin III in critically ill patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the benefits and harms of antithrombin III in critically ill patients.
DESIGN
Systematic review and meta-analysis of randomised trials.
DATA SOURCES
CENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (to November 2006); hand search of reference lists, contact with authors and experts, and search of registers of ongoing trials.
REVIEW METHODS
Two reviewers independently selected parallel group randomised clinical trials comparing antithrombin with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. Disagreements were resolved by discussion. Trials in any type of critically ill patients in intensive care were eligible. All trials, irrespective of blinding or language status, that compared any antithrombin III regimen with no intervention or placebo were included. Trials were considered to be at low risk of bias if they had adequate randomisation procedure, blinding, and used intention to treat analysis. Risk ratios with 95% confidence intervals were estimated with fixed and random effects models according to heterogeneity.
MAIN OUTCOME MEASURES
Mortality, length of stay in intensive care or hospital, quality of life, severity of sepsis, respiratory failure, duration of mechanical ventilation, incidence of surgical intervention, intervention effect among various populations, and adverse events (such as bleeding).
RESULTS
20 trials randomly assigning 3458 patients met inclusion criteria. Eight trials had low risk of bias. Compared with placebo or no intervention, antithrombin III did not reduce overall mortality (relative risk 0.96, 95% confidence interval 0.89 to 1.03). No subgroup analyses on risk of bias, populations of patients, or with and without adjuvant heparin yielded significant results. Antithrombin III increased the risk of bleeding events (1.52, 1.30 to 1.78). Heterogeneity was observed in only a few analyses.
CONCLUSION
Antithrombin III cannot be recommended for critically ill patients based on the available evidence.
Topics: Anticoagulants; Antithrombin III; Critical Care; Critical Illness; Humans; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Respiration, Artificial; Risk Factors
PubMed: 18037615
DOI: 10.1136/bmj.39398.682500.25 -
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 -
Thrombosis Journal Jan 2024Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of...
BACKGROUND
Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model.
METHOD
We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study.
RESULTS
We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I value 55%).
CONCLUSIONS
Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results.
TRIAL REGISTRATION
This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).
PubMed: 38225597
DOI: 10.1186/s12959-023-00579-z -
British Journal of Clinical Pharmacology Oct 2022Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine... (Meta-Analysis)
Meta-Analysis Review
Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69-91, I = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography-tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy.
Topics: Adult; Antithrombins; Atrial Fibrillation; Blood Coagulation Tests; Chromatography, Liquid; Dabigatran; Humans
PubMed: 35665523
DOI: 10.1111/bcp.15431 -
BMJ Clinical Evidence Nov 2010Non ST-elevation acute coronary syndrome (NSTE-ACS, here defined as unstable angina and non ST-elevation MI) is characterised by episodes of chest pain at rest or with... (Review)
Review
INTRODUCTION
Non ST-elevation acute coronary syndrome (NSTE-ACS, here defined as unstable angina and non ST-elevation MI) is characterised by episodes of chest pain at rest or with minimal exertion, which increase in frequency or severity, often with dynamic ECG changes. Between 9% and 19% of people with NSTE-ACS die in the first 6 months after diagnosis, with about half of these deaths occurring within 4 weeks of diagnosis.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: antiplatelet; antithrombin; anti-ischaemic; lipid-lowering; and invasive treatments? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 32 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aspirin, beta-blockers, calcium channel blockers, clopidogrel, direct thrombin inhibitors, glycoprotein IIb/IIIa inhibitors (oral or intravenous), heparin (low molecular weight, unfractionated), fondaparinux, nitrates, routine early cardiac catheterisation and revascularisation, statins, and warfarin.
Topics: Acute Coronary Syndrome; Acute Disease; Angina, Unstable; Humans; Myocardial Infarction; Platelet Glycoprotein GPIIb-IIIa Complex; Treatment Outcome
PubMed: 21406132
DOI: No ID Found -
Blood Sep 2011Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association... (Review)
Review
Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association between thrombophilia and failures of assisted reproduction technology (ART). A systematic search of the literature for studies reporting on thrombophilia in women undergoing ART up to April 2011 yielded 33 studies (23 evaluating anti-phospholipid antibodies, 5 inherited thrombophilia, and 5 both) involving 6092 patients. Overall, methodologic quality of the studies was poor. Combined results from case-control studies showed that factor V Leiden was significantly more prevalent among women with ART failure compared with fertile parous women or those achieving pregnancy after ART (odds ratio = 3.08; 95% confidence interval, 1.77-5.36). The prothrombin mutation, methylenetetrahydrofolate reductase mutation, deficiency of protein S, protein C, or anti-thrombin were all not associated with ART failure. Women with ART failure tested more frequently positive for anti-phospholipids antibodies (odds ratio = 3.33; 95% confidence interval, 1.77-6.26) with evidence of high degree of between-study heterogeneity (I(2) = 75%; P < .00001). Prospective cohort studies did not show significant associations between thrombophilia and ART outcomes. Although case-control studies suggest that women experiencing ART failures are more frequently positive for factor V Leiden and anti-phospholipid antibodies, the evidence is inconclusive and not supported by cohort studies.
Topics: Female; Humans; Meta-Analysis as Topic; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted; Thrombophilia
PubMed: 21705498
DOI: 10.1182/blood-2011-03-340216 -
Journal of Thrombosis and Haemostasis :... Jan 2014The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may be useful to provide patients with prognostic information and target prevention strategies.
OBJECTIVE
To conduct a systematic review to assess whether, among patients with DVT, inherited and acquired thrombophilias are associated with a risk of PTS.
METHODS
We searched the electronic databases PubMed, EMBASE, Scopus, and Web of Science for studies published from 1990 to 2013 that assessed any thrombophilia in adult DVT patients and its association with the development of PTS. We calculated odds ratios and 95% confidence intervals for PTS according to the presence of thrombophilia. Meta-analysis was performed using the random-effects model.
RESULTS
Sixteen studies were included: 13 assessed factor V Leiden (FVL), 10 assessed prothrombin mutation, five assessed protein S and C deficiencies, three assessed antithrombin deficiency, four assessed elevated FVIII levels, and six assessed antiphospholipid antibodies. None of the meta-analyses identified any thrombophilia to be predictive of PTS. Both FVL and prothrombin mutation appeared protective among studies including patients with both first and recurrent DVT and studies in which more than 50% of patients had an unprovoked DVT.
CONCLUSIONS
Our meta-analysis did not demonstrate a significant association between any of the thrombophilias assessed and the risk of PTS in DVT patients. Other biomarkers in the pathophysiological pathway may be more predictive of PTS.
Topics: Humans; Postthrombotic Syndrome; Thrombophilia
PubMed: 24406063
DOI: 10.1111/jth.12447