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Pharmacological Research Jul 2020Portal venous system thrombosis (PVST) is a life-threatening complication after splenectomy in cirrhotics patients with portal hypertension, while the application of... (Meta-Analysis)
Meta-Analysis
What intervention regimen is most effective prevention for Portal venous system thrombosis after splenectomy in cirrhotics patients with Portal hypertension? Systematic review and network meta-analysis.
Portal venous system thrombosis (PVST) is a life-threatening complication after splenectomy in cirrhotics patients with portal hypertension, while the application of intervention regimen may prevent the incidence of PVST. The aim of this network meta-analysis was to determine the most appropriate intervention regimen and application time. Several electronic databases were searched up to December 2019. We estimated summary odds ratios (OR) using pairwise and network meta-analyses with random effects for the outcome of occurrence of PVST. This work was registered with PROSPERO (CRD42019161406). The analysis was based on 19 researches, which included 1853 patients. The results drawn from the data in standard meta-analysis indicated that the application of intervention was better than no intervention use, and early application of interventions was better than delayed application in preventing the occurrence of PVST. Subsequent network meta-analysis was performed to determine the most suitable intervention regimen used early post-operation. For separate mono-therapy drug, alprostadil, antithrombin III, low molecular dextran were significantly more efficacious than others. However, mono-therapy analysis was not so close to clinical application. In the follow-up network meta-analysis, low molecular dextran combined with low molecular weight heparin exhibited the largest effect on the preventing the incidence of PVST (0.12, 0.03-0.49), followed by antithrombin III (0.12, 0.04-0.41) with low molecular dextran (0.14, 0.05-0.41). We could draw the conclusion that early application of low molecular weight heparin combined with low molecular dextran seems to be the most satisfactory treatment to prevent the incidence of PVST for patients with cirrhotic portal hypertension after splenectomy.
Topics: Dextrans; Drug Therapy, Combination; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Network Meta-Analysis; Portal Pressure; Portal Vein; Protective Factors; Risk Assessment; Risk Factors; Splenectomy; Treatment Outcome; Venous Thrombosis
PubMed: 32330553
DOI: 10.1016/j.phrs.2020.104825 -
British Journal of Haematology Aug 2018Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of...
Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty-five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs -21, -19b, and -92a, RNU2-1f, CXCL13, interleukins -6, -8, and -10, soluble interleukin-2-receptor, soluble CD19, soluble CD27, tumour necrosis factor-alfa, beta-2-microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA-21 soluble CD27, and beta-2-microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL-13, beta-2-microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.
Topics: Biomarkers, Tumor; Central Nervous System Neoplasms; Chemokine CXCL13; Humans; Neopterin; beta 2-Microglobulin
PubMed: 29808930
DOI: 10.1111/bjh.15410 -
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 -
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 -
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 -
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 -
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 Cochrane Database of Systematic... May 2015Hepatic veno-occlusive disease (VOD) is a severe complication after haematopoietic stem cell transplantation (HSCT). Different drugs with different mechanisms of action... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatic veno-occlusive disease (VOD) is a severe complication after haematopoietic stem cell transplantation (HSCT). Different drugs with different mechanisms of action have been tried in HSCT recipients to prevent hepatic VOD. However, it is uncertain whether high-quality evidence exists to support any prophylactic therapy.
OBJECTIVES
We aimed to determine the effects of various prophylactic therapies on the incidence of hepatic VOD, overall survival, mortality, quality of life (QOL), and the safety of these therapies in people undergoing HSCT.
SEARCH METHODS
We searched the Cochrane Central Registe of Controlled Trials (CENTRAL), MEDLINE, EMBASE, conference proceedings of three international haematology-oncology societies and two trial registries in January 2015, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing prophylactic therapies with placebo or no treatment, or comparing different therapies for hepatic VOD in people undergoing HSCT.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 14 RCTs. Four trials (612 participants) compared ursodeoxycholic acid with or without additional treatment versus placebo or no treatment or same additional treatment. Two trials (259 participants) compared heparin with no treatment. Two trials (106 participants) compared low molecular weight heparin (LMWH) with placebo or no treatment. One trial (360 participants) compared defibrotide with no treatment. One trial (34 participants) compared glutamine with placebo. Two trials (383 participants) compared fresh frozen plasma (FFP) with or without additional treatment versus no treatment or same additional treatment. One trial (30 participants) compared antithrombin III with heparin versus heparin. One trial compared heparin (47 participants) with LMWH (46 participants) and prostaglandin E1 (PGE1) (47 participants). No trial investigated the effects of danaparoid. The RCTs included participants of both genders with wide age range and disease spectrum undergoing autologous or allogeneic HSCT. Funding was provided by government sources (two studies), research fund (one study), pharmaceutical companies that manufactured defibrotide and ursodeoxycholic acid (two studies), or unclear source (nine studies). All RCTs had high risk of bias because of lack of blinding of participants and study personnel, or other risks of bias (mainly differences in baseline characteristics of comparison groups).Results showed that ursodeoxycholic acid may reduce the incidence of hepatic VOD (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.40 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) 15, 95% CI 7 to 50, low quality of evidence), but there was no evidence of difference in overall survival (hazard ratio (HR) 0.83, 95% CI 0.59 to 1.18, low quality of evidence). It may reduce all-cause mortality (RR 0.70, 95% CI 0.50 to 0.99; NNTB 17, 95% CI 8 to 431, low quality of evidence) and mortality due to hepatic VOD (RR 0.27, 95% CI 0.09 to 0.87; NNTB 34, 95% CI 16 to 220, very low quality of evidence). There was no evidence of difference in the incidence of hepatic VOD between treatment and control groups for heparin (RR 0.47, 95% CI 0.18 to 1.26, very low quality of evidence), LMWH (RR 0.27, 95% CI 0.06 to 1.18, very low quality of evidence), defibrotide (RR 0.62, 95% CI 0.38 to 1.02, low quality of evidence), glutamine (no hepatic VOD in either group, very low quality of evidence), FFP (RR 0.66, 95% CI 0.20 to 2.17, very low quality of evidence), antithrombin III (RR 0.13, 95% CI 0.01 to 2.15, very low quality of evidence), between heparin and LMWH (RR 1.96, 95% CI 0.80 to 4.77, very low quality of evidence), between heparin and PGE1 (RR 1.20, 95% CI 0.58 to 2.50, very low quality of evidence), and between LMWH and PGE1 (RR 0.61, 95% CI 0.24 to 1.55, very low quality of evidence). There was no evidence of difference in survival between treatment and control groups for heparin (92.6% vs. 88.7%) and defibrotide (HR 1.04, 95% CI 0.54 to 2.02, low quality of evidence). There were no data on survival for trials of LMWH, glutamine, FFP, antithrombin III, between heparin and LMWH, between heparin and PGE1, and between LMWH and PGE1. There were no data on quality of life (QoL) for any trials. Eleven trials reported adverse events. There was no evidence of difference in the frequency of adverse events between treatment and control groups except for one trial showing that defibrotide resulted in more adverse events compared with no treatment (RR 18.79, 95% CI 1.10 to 320.45). These adverse events included coagulopathy, gastrointestinal disorders, haemorrhage and microangiopathy. The quality of evidence was low or very low due to bias of study design, and inconsistent and imprecise results.
AUTHORS' CONCLUSIONS
There is low or very low quality evidence that ursodeoxycholic acid may reduce the incidence of hepatic VOD, all-cause mortality and mortality due to VOD in HSCT recipients. However, the optimal regimen is not well-defined. There is insufficient evidence to support the use of heparin, LMWH, defibrotide, glutamine, FFP, antithrombin III, and PGE1. Further high-quality RCTs are needed.
Topics: Antithrombin III; Cause of Death; Cholagogues and Choleretics; Female; Glutamine; Hematopoietic Stem Cell Transplantation; Heparin, Low-Molecular-Weight; Hepatic Veno-Occlusive Disease; Humans; Male; Plasma; Polydeoxyribonucleotides; Randomized Controlled Trials as Topic; Ursodeoxycholic Acid
PubMed: 26017019
DOI: 10.1002/14651858.CD009311.pub2 -
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 -
Journal of Vascular Surgery Feb 2014The purpose of this study was to summarize the current evidence of the association between markers of hemostasis and both the presence and size of abdominal aortic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of this study was to summarize the current evidence of the association between markers of hemostasis and both the presence and size of abdominal aortic aneurysms (AAAs).
METHODS
A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines by use of the search terms "aneurysm AND abdominal AND aortic AND coagulation" NOT "thoracic." Outcome data including concentration of hemostatic marker, number of patients, and significance level were recorded.
RESULTS
A total of 22 nonrandomized studies were included in the analysis, with a total of 9862 patients. Fibrinogen mean difference (MD) (0.43 g/L; 95% confidence interval [CI], 0.28-0.58 g/L; P ≤ .00001), D-dimer MD (325.82 ng/mL; 95% CI, 199.74-451.89 ng/mL; P ≤ .00001), and thrombin-antithrombin III complex MD (5.58 g/L; 95% CI, 3.34-7.83 g/L; P ≤ .0001) were significantly elevated in the presence of AAAs. Tissue plasminogen activator, prothrombin fragments F1+F2, and platelet count were not shown to be significantly different between patients with and those without AAAs. Meta-regression of studies reporting plasma D-dimer concentration and aneurysm diameter suggests a strong and significant association (r(2) = 0.94; P ≤ .0001).
CONCLUSIONS
This study suggests that the presence of AAAs is associated with increased fibrin turnover, fibrinolysis, and thrombin generation, as shown by increased levels of fibrinogen, D-dimer, and thrombin-antithrombin III complex. This is clinically relevant because markers of hemostasis are independent risk factors for cardiovascular events, highlighting the necessity of addressing all modifiable cardiovascular risk factors in patients with AAAs. Furthermore, the finding that plasma D-dimer concentration appears to have a linear relationship with aneurysm diameter may be useful as a future biomarker of AAAs.
Topics: Antithrombin III; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Biomarkers; Dilatation, Pathologic; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Peptide Hydrolases; Prognosis; Risk Factors
PubMed: 24461868
DOI: 10.1016/j.jvs.2013.10.088