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American Journal of Hematology Jun 2019Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for...
Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Factor Xa; Humans; Practice Guidelines as Topic; Recombinant Proteins
PubMed: 30916798
DOI: 10.1002/ajh.25475 -
Critical Care Medicine Oct 2021To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies.
DATA SOURCES
Embase, Pubmed, Web of Science, and the Cochrane Library.
STUDY SELECTION
Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage.
DATA EXTRACTION
Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event.
DATA SYNTHESIS
A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents.
CONCLUSIONS
Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
Topics: Coagulants; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Prothrombin; Recombinant Proteins
PubMed: 33967205
DOI: 10.1097/CCM.0000000000005059 -
BMJ (Clinical Research Ed.) Oct 2017To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous... (Meta-Analysis)
Meta-Analysis Review
To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy. Systematic review and bayesian meta-analysis. Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016. Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion. VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing. 36 studies were included in the meta-analysis. All thrombophilias increased the risk for pregnancy associated VTE (probabilities ≥91%). Regarding absolute risks of pregnancy associated VTE, high risk thrombophilias were antithrombin deficiency (antepartum: 7.3%, 95% credible interval 1.8% to 15.6%; post partum: 11.1%, 3.7% to 21.0%), protein C deficiency (antepartum: 3.2%, 0.6% to 8.2%; post partum: 5.4%, 0.9% to 13.8%), protein S deficiency (antepartum: 0.9%, 0.0% to 3.7%; post partum: 4.2%; 0.7% to 9.4%), and homozygous factor V Leiden (antepartum: 2.8%, 0.0% to 8.6%; post partum: 2.8%, 0.0% to 8.8%). Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3%. Women with antithrombin, protein C, or protein S deficiency or with homozygous factor V Leiden should be considered for antepartum or postpartum thrombosis prophylaxis, or both. Women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not be prescribed thrombosis prophylaxis on the basis of thrombophilia and family history alone. These data should be considered in future guidelines on pregnancy associated VTE risk.
Topics: Bayes Theorem; Evidence-Based Medicine; Female; Humans; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thrombolytic Therapy; Thrombophilia; Venous Thrombosis
PubMed: 29074563
DOI: 10.1136/bmj.j4452 -
JAMA Network Open Nov 2022Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.
OBJECTIVE
To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.
DATA SOURCES
PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.
STUDY SELECTION
The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.
RESULTS
A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.
CONCLUSIONS AND RELEVANCE
In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.
Topics: Male; Adult; Humans; Aged; Adolescent; Female; Hemorrhage; Retrospective Studies; Anticoagulant Reversal Agents; Anticoagulation Reversal; Anticoagulants; Intracranial Hemorrhages; Thromboembolism
PubMed: 36331504
DOI: 10.1001/jamanetworkopen.2022.40145 -
Journal of Thrombosis and Haemostasis :... Jul 2016Essentials We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users. The results support discouraging COC-use in women with a... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Essentials We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users. The results support discouraging COC-use in women with a natural anticoagulant deficiency. Contrary, additive risk of factor V Leiden (FVL) or prothrombin-G20210A (PT) mutation is modest. Women with a FVL/PT-mutation as single risk factor can use COCs if alternatives are not tolerated.
SUMMARY
Background Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), which is shown to be more pronounced in women with hereditary thrombophilia. Currently, WHO recommendations state that COC-use in women with hereditary thrombophilias (antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden and prothrombin-G20210A mutation) is associated with an unacceptable health risk. Objective To perform a meta-analysis evaluating the additional risk of VTE in COC-users with thrombophilia. Methods The MEDLINE and EMBASE databases were searched on 10 February 2015 for potential eligible studies. A distinction was made between 'mild' (factor V Leiden and prothrombin-G20210A mutation) and 'severe' thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin-G20210A mutation). Results We identified 12 case-control and three cohort studies. In COC-users, mild and severe thrombophilia increased the risk of VTE almost 6-fold (rate ratio [RR], 5.89; 95% confidence interval [CI], 4.21-8.23) and 7-fold (RR, 7.15; 95% CI, 2.93-17.45), respectively. The cohort studies showed that absolute VTE risk was far higher in COC-users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill-years, respectively), and these differences in absolute risks were also noted in non-affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history). Conclusion These results support discouraging COC-use in women with severe hereditary thrombophilia. By contrast, additive VTE risk of mild thrombophilia is modest. When no other risk factors are present, (e.g. family history) COCs can be offered to these women when reliable alternative contraceptives are not tolerated.
Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Cohort Studies; Contraceptives, Oral, Combined; Factor V; Female; Heterozygote; Humans; Middle Aged; Mutation; Protein C Deficiency; Protein S Deficiency; Prothrombin; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult
PubMed: 27121914
DOI: 10.1111/jth.13349 -
Journal of the American Heart... Oct 2019Background Inherited thrombophilias are well-established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial... (Meta-Analysis)
Meta-Analysis
Background Inherited thrombophilias are well-established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency) and risk of arterial ischemic stroke in adults. Methods and Results We searched PubMed, EMBASE, and Cochrane Library Databases from inception to December 31, 2018. We included case-control or cohort studies of adults reporting the prevalence of inherited thrombophilias in those with arterial ischemic stroke and subjects without arterial ischemic stroke. Two reviewers (T.C., E.D.) independently searched the literature and extracted data. Pooled odds ratios (ORs) and 95% CIs were calculated using random-effects model. We identified 68 eligible studies, which collectively enrolled 11 916 stroke patients and 96 057 controls. The number of studies reporting factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency were 56, 45, 15, 17, and 12, respectively. Compared with controls, patients with arterial ischemic stroke were significantly more likely to have the following inherited thrombophilias: factor V Leiden (OR, 1.25; 95% CI, 1.08-1.44; I=0%), prothrombin G20210A mutation (OR, 1.48; 95% CI, 1.22-1.80; I=0%), protein C deficiency (OR, 2.13; 95% CI, 1.16-3.90; I=0%), and protein S deficiency (OR, 2.26; 95% CI, 1.34-3.80; I=8.8%). Statistical significance was not reached for antithrombin deficiency (OR, 1.25; 95% CI, 0.58-2.67; I=8.8%). Conclusions Inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency) are associated with an increased risk of arterial ischemic stroke in adults. The implications of these findings with respect to clinical management of patients with ischemic stroke require further investigation.
Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Disorders, Inherited; Brain Ischemia; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Phenotype; Prognosis; Risk Assessment; Risk Factors; Stroke; Thrombophilia
PubMed: 31549567
DOI: 10.1161/JAHA.119.012877 -
Clinical Laboratory Apr 2023Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the... (Review)
Review
BACKGROUND
Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the specialized laboratory, and interpretation of findings together with clinical data, often only part of the necessary laboratory analyses can be performed in remote central laboratories. Restrictive indications for testing, as have been recommended by previous reviews on the topic, have been based on incomplete analytics, studies with small case numbers, or short observation periods, and on an inappropriate, simple risk stratification for venous thromboembolism (VTE), further subdivided into provoked and unprovoked events.
METHODS
The authors reviewed four electronic databases for all peer-reviewed and in-press articles about thrombophilia, VTE, obstetric complications, and arterial thrombosis. After confirmation for relevance to the topic, 201 articles were accepted for inclusion in this article. This review summarizes the studies relevant to the evaluation of thrombophilic conditions, and their combination with each other and with clinical risk factors, to stratify individual risk for thromboembolism and obstetric complications.
RESULTS
Thrombophilia testing requires highly skilled personnel for laboratory analysis and interpretation. Clinical conditions that influence the results as well as special preanalytical, analytical, and postanalytical aspects must be considered if valid results are to be obtained. Tests involved include the natural anticoagulants antithrombin, protein C, and protein S; the procoagulants fibrinogen (dysfibrinogen), prothrombin (mutation G20210A), factor V (Leiden mutation), factor VIII/von Willebrand factor/blood group ABO, factor IX, and factor XI; the anti-phospholipid antibodies to detect an antiphospholipid syndrome and potentially additional uncertain thrombophilic conditions. The risks of thrombophilic conditions and clinical risk factors for VTE are cumulative or even supra-additive. Scores from thrombophilic conditions and other genetic and nongenetic risk factors permit estimation of risk for first and recurrent VTE. Therapeutic strategies can be derived from this risk stratification.
CONCLUSIONS
Thrombophilia testing is indicated when the results have potential to influence the type and duration of treatment. Indications include certain patients after VTE; or patients without previous VTE but with positive family history regarding VTE or thrombophilia before major surgery, pregnancy, combined oral contraceptives, or hormone replacement therapy. Whether or not thrombophilia is present should help determine anticoagulation, hormonal contraception, or hormone replacement.
Topics: Female; Pregnancy; Humans; Venous Thromboembolism; Thrombophilia; Anticoagulants; Risk Factors
PubMed: 37057948
DOI: 10.7754/Clin.Lab.2022.220817 -
BMJ (Clinical Research Ed.) Jul 2022To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.
MAIN OUTCOME MEASURES
Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.
RESULTS
44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.
CONCLUSIONS
Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020173088.
Topics: Anticoagulants; Bayes Theorem; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitals; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35788047
DOI: 10.1136/bmj-2022-070022 -
Critical Care (London, England) Nov 2023Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear.
METHODS
A systematic search of published studies was performed on MEDLINE and EMBASE databases using standardized search equations. Ongoing studies were identified using clinicaltrials.gov. Studies investigating the use of PCC to treat TIC (on its own or in combination with other treatments) in adult major trauma patients were included. Studies involving pediatric patients, studies of only traumatic brain injury (TBI), and studies involving only anticoagulated patients were excluded. Primary outcomes were in-hospital mortality and venous thromboembolism (VTE). Pooled effects of PCC use were reported using random-effects model meta-analyses. Risk of bias was assessed for each study, and we used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence.
RESULTS
After removing duplicates, 1745 reports were screened and nine observational studies and one randomized controlled trial (RCT) were included, with a total of 1150 patients receiving PCC. Most studies used 4-factor-PCC with a dose of 20-30U/Kg. Among observational studies, co-interventions included whole blood (n = 1), fibrinogen concentrate (n = 2), or fresh frozen plasma (n = 4). Outcomes were inconsistently reported across studies with wide variation in both measurements and time points. The eight observational studies included reported mortality with a pooled odds ratio of 0.97 [95% CI 0.56-1.69], and five reported deep venous thrombosis (DVT) with a pooled OR of 0.83 [95% CI 0.44-1.57]. When pooling the observational studies and the RCT, the OR for mortality and DVT was 0.94 [95% CI 0.60-1.45] and 1.00 [95% CI 0.64-1.55] respectively.
CONCLUSIONS
Among published studies of TIC, PCCs did not significantly reduce mortality, nor did they increase the risk of VTE. However, the potential thrombotic risk remains a concern that should be addressed in future studies. Several RCTs are currently ongoing to further explore the efficacy and safety of PCC.
Topics: Adult; Humans; Child; Venous Thromboembolism; Blood Coagulation Factors; Blood Coagulation Disorders; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37919775
DOI: 10.1186/s13054-023-04688-z -
European Journal of Vascular and... Aug 2015Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE/BACKGROUND
Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The aim of this review was to evaluate the association of prothrombin G20210A and lower extremity peripheral arterial disease (PAD).
METHODS
This was a systematic review and meta-analysis of case-control studies. A systematic review of electronic databases, including MEDLINE and Embase, was conducted to assess the prevalence of prothrombin G20210A in patients with lower extremity PAD. The main outcome was the prevalence of prothrombin G20210A in patients with lower extremity PAD. The random effects model odds ratio (OR) was used as the primary outcome measure.
RESULTS
The initial electronic search identified 168 relevant abstracts of which five studies evaluating 1,524 cases of PAD and 1,553 controls were included. Prothrombin G20210A was found in 70 of 1,524 patients with lower extremity PAD and 44 of 1,553 of the controls (random effects OR 1.68, 95% confidence interval [CI] 0.8-3.2). In those with critical limb ischemia (CLI), the prevalence of prothrombin G20210A was 23 of 302 compared with 31 of 1,253 of the controls (OR 3.2, 95% CI 1.6-6.1).
CONCLUSION
Despite finding no significant association between lower extremity PAD and prothrombin G20210A, the meta-analysis suggests that the prevalence of prothrombin G20210A is significantly elevated in those with atherosclerotic occlusive disease of the lower extremities presenting with CLI. Well-designed prospective cohort studies evaluating the role of prothrombin G20210A as a predictor of disease progression or adverse vascular events are highly needed.
Topics: Chi-Square Distribution; Critical Illness; Gene Frequency; Genetic Predisposition to Disease; Humans; Ischemia; Lower Extremity; Mutation; Odds Ratio; Peripheral Arterial Disease; Phenotype; Prothrombin; Risk Assessment; Risk Factors; Thrombophilia
PubMed: 26092622
DOI: 10.1016/j.ejvs.2015.04.033