Title: Thrombosis Research

Title: Thrombosis Research

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JCR Abbreviated Title:

ISSN: 0049-3848

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Dores, G.M., Miller, M.E. and Thorpe, S.L. (1993), Platelet adhesion at low shear rate: Study of a normal population. Thrombosis Research, 69 (2), 173-184.

Full Text: 1993\Thr Res69, 173.pdf

Abstract: the use of oral contraceptives (OCs) has been associated with vascular complications. The mechanism(s) by which OCs predispose to thrombotic events remains unclear. Recent studies have demonstrated that postmenopaUSAl (PM) women who take estrogen replacement therapy (ERT) have a decreased incidence of myocardial infarction compared to those who do not take ERT. This study was undertaken to determine if healthy individuals have differences in platelet adhesion depending on hormonal status. Men, PM women taking ERT, PM women not taking ERT, OC users, and premenopaUSAl women not taking any medications were studied. Platelet studies were performed in a Hele-Shaw flow chamber at a low shear rate using platelet-rich plasma. The platelet adhesion process to subendothelial components: fibronectin, collagen I and collagen III was recorded using a 35 mm camera mounted on an inverted microscope. Photographs were taken at 30 second intervals for a total of 12 minutes and analyzed using a modified computer program which provided a numerical account of platelet adhesion. OC users had significantly higher platelet adherence to fibronectin, collagen I and collagen III compared to all other groups. All other study groups had similar platelet adhesion independent of hormonal status. These findings suggest that OCs cause increased platelet adhesion in some individuals and this may be one of the mechanisms by which OCs contribute to thrombotic events.

Keywords: Platelet Adhesion, Estrogen Replacement Therapy, Oral Contraceptives Corresponding Author, Dose Oral-Contraceptives, Vascular Subendothelium, Cardiovascular-Disease, Venous Thromboembolism, Human-Blood, Coagulation, Collagen, Surface

? Pai, M., Evans, N.S., Shah, S.J., Green, D., Cook, D. and Crowther, M.A. (2011), Statins in the prevention of venous thromboembolism: A meta-analysis of observational studies. Thrombosis Research, 128 (5), 422-430.

Full Text: 2011\Thr Res128, 422.pdf

Abstract: Introduction: Studies have established a relationship between inflammation and venous thromboembolism (VTE). Though statins modulate inflammation, it is uncertain if they prevent VTE in heterogeneous populations. A recent randomized trial demonstrated that statins prevent VTE in healthy older adults, yet this has not been well established in other groups, including younger individuals and individuals with comorbidities. The objective of this meta-analysis was to estimate the effect of statins on VTE in a heterogeneous group of adults. Methods: We systematically reviewed the effect of statins in preventing VTE in adult inpatients and outpatients. We systematically searched MEDLINE (1966-Jan 2010), EMBASE (1980-Jan 2010), Google Scholar, Cochrane Library, PapersFirst, ProceedingsFirst, and ISI Web of Science, manually reviewed references, and contacted experts. Observational studies that compared any dose of statin to no statin or placebo, examined inpatients or outpatients, and assessed VTE, pulmonary embolism, and/or deep vein thrombosis were included. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale) were independently conducted in duplicate. Results: Four cohort studies and four case-control studies met criteria. Comparing statins to control, the odds ratio for VTE was 0.67 (95% confidence interval 0.53, 0.84), and for deep vein thrombosis was 0.53 (95% confidence interval 0.22, 1.29). The association was attenuated in lower-quality studies and studies enrolling older individuals. Conclusions: Further well-designed trials are needed to evaluate the risks and benefits of statins in preventing VTE in heterogenous populations of adults, identify high-risk subgroups, and analyze cost-effectiveness of statin use for this indication. (C) 2011 Elsevier Ltd. All rights reserved.

Keywords: Adult, Adults, Association, Cardiovascular Events, Case-Control, Case-Control Studies, Cochrane, Cohort, Cohort Studies, Control, Cost-Effectiveness, Deep Vein Thrombosis, Embase, Evaluation, Google Scholar, Health, Hydroxymethylglutaryl-Coa, Inflammation, Inflammation, ISI, ISI Web of Science, MEDLINE, Meta Analysis, Meta-Analysis, Methods, Observational, Observational Studies, Older Adults, Prevention, Pulmonary Embolism, Ratio, Reductase Inhibitors, Risk, Scale, Science, Statins, Therapy, Thromboembolism, Thrombosis, Venous Thrombosis, Web of Science

? Zhao, L.X., Li, C.S., Yin, Q., Zhang, Q., Shao, R. and Fang, Y.Y. (2014), Endothelial nitric oxide synthase 894 G > T polymorphism and thrombotic disease: A meta-analysis of 17 studies involving 8808 subjects. Thrombosis Research, 134 (5), 1057-1065.

Full Text: 2014\Thr Res134, 1057.pdf

Abstract: Introduction: Endothelial nitric oxide synthase (eNOS) 894 G > T polymorphism may influence the risk of thrombotic disease, but data from published studies with low statistical power are inconclusive. To investigate the association between the gene polymorphism and thrombotic disease, a meta-analysis was performed. Materials and Methods: Case-control studies evaluating the association between the eNOS G894T polymorphism, Glu298Asp and thrombotic disease were searched in PubMed, OVID, Web of Science, Google Scholar and China Biology Medicine disc (CBM). Data were available for 4742 cases and 4066 controls from 17 studies. Results: In all, although there was a significant association between G894T and thrombotic disease (G/T + T/T vs. G/G: OR = 1.364, 95% CI = 1.126-1.652, P = 0.001; T/T vs. G/T + G/G: OR = 1.861, 95% CI = 1.207-2.870, P = 0.005; TT vs. GG: OR = 1.938, 95% CI = 1.244-3.021, P = 0.003; G/T vs. G/G: OR = 1.225, 95% CI = 1.022-1.469, P = 0.028), there was significant heterogeneity among studies (P* < 0.001). In subgroup analysis, there was significant association with no heterogeneity in venous thrombosis (G/T + T/T vs. G/G: OR = 1.409, 95% CI = 1.135-1.750, P = 0.002, P* = 0.508; T/T vs. G/G: OR = 1.640, 95% CI = 1.011-2.660, P = 0.045, P* = 0.333; G/T vs. G/G: OR = 1.357, 95% CI = 1.082-1.701, P = 0.008, P* = 0.595) and in Asian population (G/T + T/T vs. G/G: OR = 1.722, 95% CI = 1.443-2.055, P < 0.001, P* = 0.541; T/T vs. G/T + G/G: OR = 2.357, 95% CI = 1.389-4.000, P = 0.001, P* = 0.908; T/T vs. G/G: OR = 2.813, 95% CI = 1.645-4.810, P < 0.001, P* = 0.969; G/T vs. G/G: OR = 1.645, 95% CI = 1.370-1.975, P < 0.001, P* = 0.489). Conclusions: Findings of this meta-analysis demonstrated that eNOS G894T polymorphism may be a risk factor for venous thrombosis, and in Asia the polymorphism may increase the risk of developing thrombotic disease. (C) 2014 Elsevier Ltd. All rights reserved.

Keywords: Analysis, Asia, Asian, Association, Atherosclerosis, Biology, Carotid Atherosclerosis, China, Chinese Population, Common Variant, Coronary-Artery-Disease, Data, Developing, Disease, From, G894t Polymorphism, Gene, Gene Polymorphism, Gene Polymorphisms, Gg, Google, Google Scholar, Heterogeneity, Hyperhomocysteinemia, Independent Risk Factor, Influence, Materials, Medicine, Meta Analysis, Meta-Analysis, Metaanalysis, Methods, Nitric Oxide, Nitric Oxide Synthase, Nov, Oxide, P, Polymorphism, Population, Power, Pubmed, Recurrent Venous Thrombosis, Results, Rights, Risk, Risk Factor, Science, Statistical Power, Thrombosis, Venous Thrombosis, Web, Web Of Science

? Liu, M.J., Yuan, X., Qiu, X.M., Shan, X.X., Lin, D.J. and Zhu, L. (2015), Prognostic role of heart-type fatty acid binding protein in pulmonary embolism: A meta-analysis. Thrombosis Research, 135 (1), 20-25.

Full Text: 2015\Thr Res135, 20.pdf

Abstract: Introduction: Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Our aim was to evaluate the available evidence on the accuracy of H-FABP for predicting the prognosis of adverse clinical outcomes (defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, endotracheal intubation, use of vasopressors, thrombolysis, surgical embolectomy, or admission to the intensive care unit) or mortality in patients with acute PE. Methods: Unrestricted searches of PubMed, the Cochrane Library, Web of Science and Science Direct were performed using the terms of “H-FABP” or “heart-type fatty acid binding protein” and (“pulmonary embolism” or “pulmonary thromboembolism”). A random-effect model was used to pool study results; chi(2) and I-2 testing was used to test for heterogeneity. Data of six studies were included in this analysis. Results: 34 of 119(28.57%; 95%CI, 20.42%-36.72%) patients with elevated H-FABP levels had adverse events during follow-up compared with 24 of 475 (5.05%; 95%CI, 3.08%-7.02%) patients with normal levels. High H-FABP levels were associated with a high risk of occurrence of adverse clinical outcome (pooled OR, 10.81; 95%CI, 3.92-29.83). Conclusion: The results of this meta-analysis indicate that H-FABP is a good predictor for adverse outcomes in patients with acute PE. (C) 2014 Elsevier Ltd. All rights reserved.

Keywords: Accuracy, Adverse Clinical Outcome, Adverse Events, Adverse Outcomes, Analysis, Binding, Cardiopulmonary, Cardiopulmonary Resuscitation, Care, Clinical, Clinical Outcomes, Data, Death, Embolism, Events, Evidence, Factors, Fatty Acid, Follow-Up, Heart-Type Fatty Acid Binding Protein, Heterogeneity, Injury, Intensive Care, Intensive Care Unit, Intubation, Marker, Markers, Meta Analysis, Meta-Analysis, Metaanalysis, Methods, Model, Morbidity, Mortality, Myoglobin, Natriuretic Peptide, Normal, Normotensive Patients, Outcome, Outcomes, Patients, Plasma, Predictor, Prognosis, Prognostic, Protein, Pubmed, Pulmonary Embolism, Recent, Results, Resuscitation, Right-Ventricular Dysfunction, Rights, Risk, Risk Stratification, Science, Testing, Thrombolysis, Troponin, Vasopressors, Web, Web of Science

? Yin, Y.W., Wang, Q., Sun, Q.Q., Hu, A.M. and Liu, H.L. (2015), ATP-binding cassette transporter 1 C69T and V825I polymorphisms in the development of atherosclerosis: A meta-analysis of 18,320 subjects. Thrombosis Research, 135 (1), 130-136.

Full Text: 2015\Thr Res135, 130.pdf

Abstract: Introduction: ATP-binding cassette transporter 1 (ABCA1), a member of the ATP-binding cassette family, plays a critical role in the development of atherosclerosis (AS). This meta-analysis was performed to assess the associations of ABCA1 C69T and V8251 polymorphisms with AS susceptibility. Materials and methods: A comprehensive search was conducted to identify all eligible studies from PubMed, Embase, Web of Science, Cochrane database, CBMclisc, CNK1 and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All statistical analyses were done with Review Manager 5.1.4 and Stala 11.0. Results: Eleven articles involving 14 studies were included in the final meta-analysis. For the ABCA1 C69T polymorphism, six studies involving 1854 AS cases and 5744 controls were combined showing significant association between this variant and AS risk (for T allele vs. C allele: OR_1.44,95% Cl_1.04-1.24, p_0.005; for T/T vs. C/C: OR = 1.39,95% CI = 1.12-1.73, p = 0.003; for LT vs. C/T + C/C: OR = 1.34, 95% CI = 1.09-1.65, p = 0.006; for T/T + C/T vs. C/C: OR = 1.13, 95% Cl = 1.01-1.27, p = 0.040). For the ABCA1 V8251 polymorphism, eight studies involving 2026 AS cases and 8696 controls were combined. There was no significant association between the variant and AS risk (for 1 allele vs. V allele: OR = 1.18,95% Cl = 0.90-1.53, p = 0.230; for I/I vs.V/ V: OR = 1.29,95% Cl = 0.75-2.23, p = 0.360; for II vs. V/I + V;V: OR = 1.40,95% Cl = 0.87-2.26, p = 0.160; for I/I + V/I vs. V/V OR = 1.15, 95% Cl = 1.00-1.33, p = 0.060). Conclusions: This meta-analysis suggested that the ABCA1 C69T polymorphism was associated with an increased AS risk. Furthermore, there was no significant association between the ABCA1 V8251 polymorphism and AS risk. (C) 2014 Elsevier Ltd. All rights reserved.

Keywords: Abca1, Analyses, Articles, Association, Atherosclerosis, Atp-Binding Cassette Transporter 1, Coronary-Artery-Disease, Database, Development, Family, From, Genetic Association, Google, Google Scholar, Heart-Disease, Heterogeneity, Materials, Meta Analysis, Meta-Analysis, Metaanalysis, Methods, Polymorphism, Polymorphisms, Population, Pubmed, References, Results, Review, Rights, Risk, Role, Science, Statistical Analyses, Stroke, Susceptibility, Tangier-Disease, Transporter, Type-2 Diabetes-Mellitus, Web, Web of Science

? Li, X.Q., Yang, J., Wang, X.Y., Xu, Q., Zhang, Y.X. and Yin, T. (2015), Clinical benefits of pharmacogenetic algorithm-based warfarin dosing: Meta-analysis of randomized controlled trials. Thrombosis Research, 135 (4), 621-629.

Full Text: 2015\Thr Res135, 621.pdf

Abstract: Background: Pharmacogenetic (PG) algorithms were proposed to predict warfarin therapeutic dose more accurately. However, the clinical efficacy of the strategy over the standard treatment was not consistently proven. Methods: We conducted a meta-analysis of the published randomized controlled trials (RCTs) comparing PG algorithm-based warfarin dosing (PG group) with clinical or standard protocols (STD group). The PUBMED, EMBASE, Cochrane Library and Web of Science databases were searched up to June 2014. Results: A total of 10 RCTs were retrieved for the meta-analysis with the inclusion of 2,601 participants. Primary analysis showed both major bleeding (2.65% versus 4.75%; RR: 0.57, 95% CI: 0.37-0.90, P = 0.02) and thromboembolic events (0.59% versus 1.88%; RR: 0.38, 95% CI: 0.17-0.85, P = 0.02) were significantly lower in PG than in STD group. There was a trend towards increased percentage of time in therapeutic range (%TTR) [mean difference (MD): 4.65, 95% CI: 0.01-9.29, P = 0.05] in PG group, but no difference was observed for over-anticoagulation (INR > 4). Subgroup analyses showed significant reduction of both major bleeding and thromboembolic events in PG group when the follow-up time was more than 1 month. After stratified by different PG algorithms, significant major bleeding reduction could be found in PG group when warfarin indication or co-medication of amiodarone was integrated in the algorithms. Conclusion: PG algorithm-guided warfarin anticoagulation is beneficial for the reduction of both major bleeding and thromboembolic events compared with standard dosing strategy. The benefits may be prominent in patients with longer follow-up time, or guided by refined PG algorithms. (C) 2015 Elsevier Ltd. All rights reserved.

Keywords: Algorithms, Analyses, Analysis, Anticoagulation, Benefits, Bleeding, Bleeding Complications, Chinese Patients, Clinical, Cyp2c9, Databases, Efficacy, Embase, Events, Follow-Up, Indication, Initiating Oral Anticoagulation, Integrated, Intensity, Meta Analysis, Meta-Analysis, Metaanalysis, Methods, P, Patients, Pharmacogenetics, Protocols, Randomized, Randomized Controlled Trials, Reduction, Results, Rights, Risk, Science, Standard, Std, Strategy, Therapeutic, Therapy, Thromboembolism, Treatment, Trend, Vitamin-K Antagonists, Vkorc1 Genotypes, Warfarin, Web, Web Of Science, Web Of Science Databases

? Sun, Y.F., Wu, Z.T., Li, S., Qin, X., Li, T.J., Xie, L., Deng, Y. and Chen, J.Q. (2015), Impact of gamma-glutamyl carboxylase gene polymorphisms on warfarin dose requirement: A systematic review and meta-analysis. Thrombosis Research, 135 (4), 739-747.

Full Text: 2015\Thr Res135, 739.pdf

Abstract: Background: The Gamma-glutamyl carboxylase (GGCX) gene, as with Vitamin K Epoxide Reductase Complex Subunit 1(VKORC1), CytochromeP450 Complex Subunit 14 F2 (CYP4F2) and CytochromeP450 Complex Subunit2C9 (CYP2C9), is a candidate predictor for appropriate maintenance warfarin dose. However, the association between GGCX gene polymorphisms and warfarin dose requirement is still controversial. To quantify the influence of GGCX polymorphisms on warfarin dose requirements, we performed a systematic review and meta-analysis. Methods: According to PRISRM statement (Preferred reporting items for systematic reviews and meta-analyses), a comprehensive literature search was undertaken through August 2014 looking for eligible studies in Embase, Pubmed, Web of Science and the Cochrane Library. The impact of GGCX polymorphisms on mean daily warfarin dose (MDWD) was counted by means of Z test. RevMan 5.2.7 software (developed by the Cochrane Collaboration) was applied to analyze the relationship between GGCX gene polymorphisms and warfarin dose requirements. Results: Nineteen articles including 21 studies with a total of 6957 patients were included in the meta-analysis. Among three investigated single nucleotide polymorphisms (SNPs), rs11676382 showed higher CC genotype frequencies in Asian than those in Caucasian(97.7% vs. 86.9%); patients who were “G carriers” (that is, carried the GGCX rs11676382 CG or GG genotypes) required 27% lower warfarin dose than CC genotype[95% Confidence Interval(CI) = 17%-37%, P = 0.000, I-2% = 82.0 and PQ = 0.000], moreover, stratified analysis by ethnicity showed similar results in Caucasian(23% lower, 95% CI = 12%-33%), but not in Asian. With respect to genetic variation of rs699664 and rs121714145 SNPs, no significant impact on warfarin dose requirements were demonstrated. Conclusions: This meta-analysis suggested that GGCX rs11676382 polymorphism may be one of factors affecting the dose of warfarin requirement, and the effects are different in different ethnicities. Further studies about this topic in different ethnicities with larger samples are expected to be conducted to validate our results. (C) 2015 The Authors. Published by Elsevier Ltd.

Keywords: African-Americans, Analysis, Articles, Asian, Association, Cell Distribution Width, Chinese Patients, Cochrane Collaboration, Collaboration, Cyp2c9, Cytochrome P4502c9, Effects, Ethnicity, Factors, Gamma-Glutamyl Carboxylase, Gene, Genetic, Genotype, Gg, Ggcx Polymorphisms, Impact, Influence, K Epoxide Reductase, Literature, Literature Search, Meta Analysis, Meta-Analyses, Meta-Analysis, Metaanalysis, Methods, P, Patients, Polymorphism, Polymorphisms, Population, Predictor, Reporting, Requirement, Results, Review, Reviews, Science, Sequence Variations, Software, Systematic, Systematic Review, Systematic Reviews, Topic, Vkorc1, Warfarin, Web, Web Of Science

? Di Minno, M.N.D., Ambrosino, P., Ageno, W., Rosendaal, F., Di Minno, G. and Dentali, F. (2015), Natural anticoagulants deficiency and the risk of venous thromboembolism: A meta-analysis of observational studies. Thrombosis Research, 135 (5), 923-932.

Full Text: 2015\Thr Res135, 923.pdf

Abstract: Introduction: Natural anticoagulants deficiency (antithrombin [AT], protein C [PC], protein S [PS]) is a rare, but potent risk factor for venous thromboembolism (VTE). We performed a meta-analysis of observational studies evaluating the impact of inherited natural anticoagulants deficiency on VTE risk. Materials and Methods: Case-control and cohort studies evaluating the association of these abnormalities with VTE were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: Twenty-one studies were included in the analysis. Thirteen studies (3,452 cases and 11,562 controls) showed an increased risk of first VTE in AT deficient subjects compared to controls (OR: 16.26, 95% CI: 9.90-26.70; P < 0.00001). An increased risk of first VTE was also found in PC (11 studies, 2,554 cases and 9,355 controls; OR: 7.51, 95% CI: 3.21-17.52; P < 0.00001) and PS deficient patients (14 studies, 4,955 cases and 9,267 controls; OR: 5.37; 95% CI: 2.70-10.67; P < 0.00001) compared to controls. Evaluating the risk of VTE recurrence, we found a significant association with AT (4 studies, 142 cases and 1,927 controls; OR: 3.61; 95% CI: 1.46-8.95; P = 0.006) and with PC (2 studies, 80 cases and 546 controls; OR: 2.94; 95% CI: 1.43-6.04; P = 0.03), but not with PS deficiency (2 studies, 57 cases and 589 controls; OR: 2.52; 95% CI: 0.89-7.16; P = 0.08). Sensitivity and subgroup analyses confirmed these results. The association among natural anticoagulants deficiency and VTE was maximal for patients with unprovoked events. Conclusion: The VTE risk is increased in patients with natural anticoagulants deficiency, but additional studies are warranted to better assess the risk of VTE recurrence. (C) 2015 Elsevier Ltd. All rights reserved.

Keywords: Analyses, Analysis, Antithrombin, Antithrombin Deficiency, Association, At, Cohort, Databases, Deep-Vein Thrombosis, Events, Familial Thrombophilia, First, Hereditary Deficiencies, Impact, Inherited Thrombophilia, Meta-Analysis, Metaanalysis, Natural, Observational, Observational Studies, Outpatients, P, Patients, Prevalence, Prospective Cohort, Protein, Protein C, Protein S, Protein-S Deficiency, Pubmed, Recurrence, Rights, Risk, Risk Factor, Science, Scopus, Thromboembolism, Venous Thromboembolism, Web Of Science