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Thrombosis Research Jun 2022Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of... (Meta-Analysis)
Meta-Analysis Review
Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis.
BACKGROUND
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of aPLs with thrombotic events depends on the number of positive tests. Besides the three classical tests to classify APS, phosphatidylserine/prothrombin complex autoantibodies (aPS/PT) are increasingly used to better define this condition. The aim of this systematic review was to evaluate the prevalence of aPS/PT in general and according to antiphospholipid antibody profiles in patients with APS.
METHODS
A systematic search of PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021 was carried out according to PRISMA guidelines. Proportions and 95% confidence intervals (CIs) were calculated using random-effects model. Publication biases were evaluated via visualization of funnel plots along with Egger's and Begg's tests.
RESULTS
Twenty-one articles about the prevalence of aPS/PT in 1853 patients with APS were deemed eligible and analyzed according to the inclusion criteria. Pooled prevalence of aPS/PT IgG alone, IgM alone, and IgG/M were 50.0%, 45.0%, and 65.0%, respectively. No significant publication bias was detected from funnel plots or Egger's and Begg's tests. When the prevalence of aPS/PT was calculated in homogeneous aPLs, a much higher rate of pooled prevalence of aPS/PT IgG/M in patients positive for Lupus Anticoagulant (84.5%) and in those with triple positivity (83.4%) was found.
CONCLUSIONS
These data show a high rate of aPS/PT positivity in patients with APS (especially in those positive for LAC) but further studies are needed to ascertain whether this test might be useful in the laboratory classification criteria of APS.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Immunoglobulin G; Phosphatidylserines; Prevalence; Prothrombin; Thrombosis
PubMed: 35526513
DOI: 10.1016/j.thromres.2022.04.021 -
Thrombosis Research Feb 2015Thrombophilia is reported to be a candidate etiology of recurrent pregnancy loss (RPL). No conclusive results on the association between prothrombin G20210A mutation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thrombophilia is reported to be a candidate etiology of recurrent pregnancy loss (RPL). No conclusive results on the association between prothrombin G20210A mutation and RPL have been reported.
METHODS
We undertook a systematic review and meta-analysis of 37 case-control studies using a comprehensive electronic search on papers published by May 2014. We studied 5400 cases and 4640 controls to investigate the potential association between G20210A and RPL. In this review, we define RPL as more than 2 miscarriages.
RESULTS
A significant association was found between G20210A and RPL, with a combined odds ratio (OR) of 1.81 (95% confidence interval [CI]: 1.26-2.60). However, the risks differed in the subgroup analyses, categorized by study sites, maternal age, and type of miscarriages. The pooled OR remained significant in European studies (OR: 1.80, 95% CI: 1.35-2.41), whereas in the Middle-Eastern studies, it was not significant (OR: 2.39, 95% CI: 0.96-5.92). The risk of RPL was significantly higher in women older than 29 years (OR: 1.91, 95% CI: 1.61-6.11), and a positive relationship was only observed between prothrombin G20210A mutation and fetal loss, but not embryonic loss. There was no evidence of publication bias in any of the analyses. The sensitivity analyses showed that the findings were quite stable.
CONCLUSION
This meta-analysis suggests that the G20210A prothrombin mutation increases the risk of RPL (fetal loss, primary RPL, or secondary RPL), particularly in Europeans and women older than 29 years. We recommend further screening in more specific groups among women.
Topics: Abortion, Habitual; Adult; Female; Humans; Mutation; Pregnancy; Prothrombin; Thrombophilia
PubMed: 25528068
DOI: 10.1016/j.thromres.2014.12.001 -
Expert Review of Gastroenterology &... 2023The incidence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing globally. We aimed to assess the performance of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The incidence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing globally. We aimed to assess the performance of alpha-fetoprotein (AFP), AFP-L3, des-gamma-carboxy prothrombin (DCP), and GALAD score in detecting NAFLD-related HCC.
METHODS
We searched the relevant literature in PubMed, Embase and Cochrane. Conventional and network meta-analyses were performed for sensitivity, specificity, Youden index (YI), and the area under the summary receiver operator characteristic curve (AUC).
RESULTS
Fifteen studies involving 2031 NAFLD participants were included in this meta-analysis. When detecting early-stage NAFLD-related HCC, GALAD score and DCP process excellent performance. The sensitivity and AUC of DCP (0.60, 0.74, respectively) were higher than AFP (0.34, 0.59, respectively). The network meta-analysis showed that DCP and GALAD score had similar performance. In detecting all-stage NAFLD-related HCC, GALAD score (sensitivity = 0.87; YI = 0.77) performed better than AFP (sensitivity = 0.56; YI = 0.50), AFP-L3 (sensitivity = 0.39; YI = 0.36) and DCP (sensitivity = 0.73; YI = 0.62). Network meta-analysis obtained consistent results with conventional meta-analysis.
CONCLUSIONS
Due to the lower cost-effectiveness, DCP was more suitable for detecting early NAFLD-related HCC. AFP could be used in detecting all-stage NAFLD-related HCC.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Liver Neoplasms; Protein Precursors; Prothrombin; Biomarkers; Biomarkers, Tumor
PubMed: 37929312
DOI: 10.1080/17474124.2023.2279175 -
International Journal of Environmental... Oct 2019Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events;... (Meta-Analysis)
Meta-Analysis
Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275-2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398-3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920-2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293-4.860), cefamandole (OR 3.247, 95% CI 1.083-9.733), and moxalactam (OR 3.367, 95% CI 1.725-6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.
Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Hypoprothrombinemias; Male
PubMed: 31623191
DOI: 10.3390/ijerph16203937 -
Journal of Clinical Medicine May 2020The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but... (Review)
Review
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.
PubMed: 32403255
DOI: 10.3390/jcm9051420 -
Clinical Gastroenterology and... Nov 2014We conducted a systematic review and meta-analysis to evaluate the associations of the coagulation factor V (encoded by F5) Leiden (FVL) or prothrombin (encoded by F2)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We conducted a systematic review and meta-analysis to evaluate the associations of the coagulation factor V (encoded by F5) Leiden (FVL) or prothrombin (encoded by F2) G20210A mutation with Budd-Chiari syndrome or portal vein thrombosis (PVT).
METHODS
Relevant articles were identified in searches of the PubMed, EMBASE, Cochrane Library, and ScienceDirect databases. The prevalence of the FVL and prothrombin G20210A mutations were compared between patients with Budd-Chiari syndrome or PVT without cirrhosis and healthy individuals (controls) and between patients with cirrhosis, with and without PVT. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
RESULTS
We initially identified 869 articles, and included 27 in our final analysis. Compared with controls, patients with Budd-Chiari syndrome had a significantly higher prevalence of the FVL mutation (OR, 6.21; 95% CI, 3.93-9.79) and a similar prevalence of the prothrombin G20210A mutation (OR, 1.90; 95% CI, 0.69-5.23); patients with PVT without cirrhosis had a significantly higher prevalence of the FVL mutation (OR, 1.85; 95% CI, 1.09-3.13) or the prothrombin G20210A mutation (OR, 5.01; 95% CI, 3.03-8.30). Compared with patients with cirrhosis without PVT, patients with cirrhosis and PVT had a significantly higher prevalence of the FVL mutation (OR, 2.55; 95% CI, 1.29-5.07). We observed a trend toward a higher prevalence of the prothrombin G20210A mutation in patients with cirrhosis and PVT, but the difference was not statistically significant (OR, 2.93; 95% CI, 0.94-9.07).
CONCLUSIONS
Based on a meta-analysis, the FVL mutation is associated with an increased risk of Budd-Chiari syndrome, PVT without cirrhosis, and PVT in cirrhosis. The prothrombin G20210A mutation is associated with PVT, but not Budd-Chiari syndrome. Studies are needed to confirm these findings in different racial and ethnic groups.
Topics: Budd-Chiari Syndrome; Factor V; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Portal Vein; Prothrombin; Thrombosis
PubMed: 24793031
DOI: 10.1016/j.cgh.2014.04.026 -
PloS One 2016To compare the prevalence of prothrombin G20210A in patients with objectively confirmed cerebral vein or cortical vein thrombosis against healthy controls, and evaluate... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the prevalence of prothrombin G20210A in patients with objectively confirmed cerebral vein or cortical vein thrombosis against healthy controls, and evaluate geographical variations.
DESIGN
Systematic review and meta-analysis of case control studies.
METHODS
We conducted a systematic review of electronic databases including MEDLINE and EMBASE. The main outcome was the prevalence of prothrombin G20210A in patients with objectively confirmed cerebral vein or cortical vein thrombosis; we also analyzed individual country variations in the prevalence. The random-effects model OR was used as the primary outcome measure.
RESULTS
In total 19 studies evaluated 868 cases of cerebral venous thrombosis and 3981 controls. Prothrombin G20210A was found in 103/868 of the patients with cerebral venous thrombosis and 105/3999 of the healthy controls [random effects pooled OR 5.838, 95% CI 3.96 to 8.58; I217.9%]. The prevalence of prothrombin G20210A was significantly elevated in Italian studies (OR 9.69), in Brazilian studies (OR 7.02), and in German studies (OR 3.77), but not in Iranian studies (OR 0.98).
CONCLUSION
Prothrombin G20210A is significantly associated with cerebral venous thrombosis when compared to healthy controls, although this association is highly dependent on the country of origin.
Topics: Brazil; Case-Control Studies; Cerebral Veins; Gene Frequency; Germany; Humans; Iran; Italy; Linkage Disequilibrium; Odds Ratio; Point Mutation; Prevalence; Prothrombin; Venous Thrombosis
PubMed: 27031503
DOI: 10.1371/journal.pone.0151607 -
Journal of Acute Medicine Sep 2021Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional...
BACKGROUND
Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional administration of prothrombin complex concentrate (PCC) was proposed to bring about further coagulative benefit. However, investigations evaluating the efficacy as well as corresponding side effects were scarce and inconsistent. The aim of this study was to systematically review current literature and to perform a meta-analysis comparing FFP+PCC with FFP alone.
METHODS
Web search followed by manual interrogation was performed to identify relevant literatures fulfilling the following criteria, subjects as TIC patients taking no baseline anticoagulants, without underlying coagulative disorders, and reported clinical consequences. Those comparing FFP alone with PCC alone were excluded. Comprehensive Meta-analysis software was utilized, and statistical results were delineated with odd ratio (OR), mean difference (MD), and 95% confidence interval (CI). I was calculated to determine heterogeneity. The primary endpoint was set as all-cause mortality, while the secondary endpoint consisted of international normalized ratio (INR) correction, transfusion of blood product, and thrombosis rate.
RESULTS
One hundred and sixty-four articles were included for preliminary evaluation, 3 of which were qualified for meta-analysis. A total of 840 subjects were pooled for assessment. Minimal heterogeneity was present in the comparisons (I < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, < 0.001), whilst the rate showed no difference ( = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells ( < 0.001) and plasma ( < 0.001), but not platelet ( = 0.615). The incidence of deep vein thrombosis was comparable in the two groups ( = 0.460).
CONCLUSIONS
Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.
PubMed: 34595091
DOI: 10.6705/j.jacme.202109_11(3).0001 -
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 -
European Journal of Pediatrics May 2017To systematically evaluate the effectiveness of prothrombin complex concentrate (PCC) in neonates and infants, we performed a systematic review and meta-analysis based... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
To systematically evaluate the effectiveness of prothrombin complex concentrate (PCC) in neonates and infants, we performed a systematic review and meta-analysis based on current evidence. Quality of studies was assessed by Cochrane Collaboration's risk of bias tool and Newcastle-Ottawa quality assessment scale. For dichotomous data, we obtained the number of events and total number and calculated the relative risk (RR) with 95% confidence intervals (CI). For continuous variables, we obtained mean and standard deviation (SD) values and calculated mean difference (MD) with 95% CI. We identified six trials and two cohort studies. For trials, selection bias and performance bias were high, while detection bias, attrition bias, and reporting bias were relatively low. For cohort studies, selection bias was low. Both individual studies and meta-analysis failed to find any benefit of PCC on mortality. Meta-analysis also failed to show any benefit in reducing intracranial hemorrhage. The effectiveness of PCC on the correction of hemostatic defects was inconsistent among studies. In addition, PCC was not more effective than fresh frozen plasma (FFP) in correcting hemostatic defects.
CONCLUSION
There is insufficient evidence to allow a recommendation for use of PCC in neonates and infants. What is Known: • Prothrombin Complex Concentrate is becoming increasingly used off-label for treatment of neonates and infants with severe bleeding or risk of severe bleeding. • Some case reports showed PCC seemed to be effective for infants and children with coagulation factor deficiency, but evidence about the effectiveness of PCC to reverse serious Vitamin K Deficiency Bleeding is limited. What is New: • As far as we know, this is the first systematic review that evaluates the effectiveness of PPC in neonates with bleeding or risk of bleeding. • There is insufficient evidence to allow a recommendation for use of PCCs in neonates and infants.
Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Cohort Studies; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Off-Label Use; Randomized Controlled Trials as Topic; Risk; Vitamin K Deficiency
PubMed: 28281092
DOI: 10.1007/s00431-017-2877-0