-
JAMA Nov 2020Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from...
IMPORTANCE
Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.
OBSERVATIONS
PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin.
CONCLUSIONS AND RELEVANCE
Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.
Topics: Age Factors; Biomarkers; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Life Style; Lower Extremity; Medical Illustration; Postthrombotic Syndrome; Predictive Value of Tests; Risk Factors; Sex Factors; Symptom Assessment; Thrombectomy; Thrombophilia; Ultrasonography; Vena Cava Filters; Venous Thromboembolism; Warfarin
PubMed: 33141212
DOI: 10.1001/jama.2020.17272 -
Future Cardiology May 2022To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial... (Meta-Analysis)
Meta-Analysis Review
To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Dabigatran; Fibrinolytic Agents; Humans; Network Meta-Analysis; Pyridones; Rivaroxaban; Stroke; Vitamin K
PubMed: 35360925
DOI: 10.2217/fca-2021-0120 -
The Lancet. Oncology Oct 2019Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during...
Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Topics: Anticoagulants; Central Venous Catheters; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Vena Cava Filters; Venous Thromboembolism; Vitamin K
PubMed: 31492632
DOI: 10.1016/S1470-2045(19)30336-5 -
Journal of Thrombosis and Haemostasis :... Oct 2021The usefulness of D-dimer measurement to rule out venous thromboembolism (VTE) during pregnancy is debated. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The usefulness of D-dimer measurement to rule out venous thromboembolism (VTE) during pregnancy is debated.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the safety of D-dimer to rule out acute VTE in pregnant women with suspected pulmonary embolism and/or deep vein thrombosis.
METHODS
Two reviewers independently identified studies through PubMed and Embase until June 2021, week 1. We supplemented our search by manually reviewing reference lists of all retrieved articles, clinicalTrials.gov, and reference literature. Prospective or retrospective studies in which a formal diagnostic algorithm was used to evaluate the ability of D-dimer to rule out VTE during pregnancy were eligible.
RESULTS
We identified 665 references through systematic database and additional search strategies; 45 studies were retrieved in full, of which four were included, after applying exclusion criteria. Three studies were prospective, and one had a retrospective design. The 3-month thromboembolic rate in pregnant women left untreated after a negative D-dimer was 1/312 (0.32%; 95% CI, 0.06-1.83). The pooled estimate values were 99.5% for sensitivity (95% CI, 95.0-100.0; I², 0%) and 100% for negative predictive value (95% CI, 99.19-100.0; I², 0%). The prevalence of VTE and the yield of D-dimer were 7.4% (95% CI, 3.8-12; I², 83%) and 34.2% (95% CI, 15.9-55.23; I², 89%) respectively.
CONCLUSION
Our results suggest that D-dimer allows to safely rule out VTE in pregnant women with suspected VTE and a disease prevalence consistent with a low/intermediate or unlikely pretest probability.
Topics: Female; Fibrin Fibrinogen Degradation Products; Humans; Pregnancy; Prospective Studies; Pulmonary Embolism; Retrospective Studies; Venous Thromboembolism
PubMed: 34161671
DOI: 10.1111/jth.15432 -
The Cochrane Database of Systematic... May 2022Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
OBJECTIVES
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
METHODS
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty). We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
MAIN RESULTS
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows. First-line treatments Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD -105.71 mL/cycle, 95% CI -201.10 to -10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD -80.32 mL/cycle, 95% CI -127.67 to -32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD -76.93 mL/cycle, 95% CI -153.82 to -0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD -40.67 mL/cycle, -84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty. We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction. Second-line treatments Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence). Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).
AUTHORS' CONCLUSIONS
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Topics: Amenorrhea; Antifibrinolytic Agents; Child, Preschool; Female; Humans; Menorrhagia; Network Meta-Analysis; Progestins; Quality of Life; Systematic Reviews as Topic
PubMed: 35638592
DOI: 10.1002/14651858.CD013180.pub2 -
Chest May 2023The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario.
RESEARCH QUESTION
What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures?
STUDY DESIGN AND METHODS
A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate.
RESULTS
In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE.
INTERPRETATION
The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Warfarin; Fibrinolytic Agents; Hemorrhage; Vitamin K; Administration, Oral
PubMed: 36462533
DOI: 10.1016/j.chest.2022.11.032 -
Stroke Oct 2022High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis.
METHODS
This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs).
RESULTS
Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I=0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I=0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I=0%), death (RR, 1.14 [95% CI, 0.54-2.43], I=1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I=0%).
CONCLUSIONS
This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.
Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Thrombosis; Prospective Studies; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin
PubMed: 35938419
DOI: 10.1161/STROKEAHA.122.039579 -
Expert Review of Hematology Nov 2020COVID-19 disease has spread worldwide from December 2019 to the present day; the early stage of this disease can be associated with high D-dimer, prolonged PT, and...
INTRODUCTION
COVID-19 disease has spread worldwide from December 2019 to the present day; the early stage of this disease can be associated with high D-dimer, prolonged PT, and elevated levels of fibrinogen, indicating activation of coagulation pathways and thrombosis. In this article, we analyze the levels of D-dimer in patients with COVID-19.
AREA COVERED
In the current study, three databases, PubMed, Scopus, Web of Science, searched using related keywords and information extracted from articles such as location, sample size, gender, age, coagulation test values, patient results, and disease severity.
EXPERT OPINION
D-dimer level is one of the measures used in patients to detect thrombosis. Studies have reported an increase in D-dimer and fibrinogen concentrations in the early stages of COVID-19 disease a 3 to 4-fold rise in D-dimer levels is linked to poor prognosis. In addition, underlying diseases such as diabetes, cancer, stroke, and pregnancy may trigger an increase in D-dimer levels in COVID-19 patients. Measuring the level of D-dimer and coagulation parameters from the early stage of the disease can also be useful in controlling and managing of COVID-19 disease.
Topics: Biomarkers; COVID-19; Fibrin Fibrinogen Degradation Products; Humans; Prognosis; SARS-CoV-2
PubMed: 32997543
DOI: 10.1080/17474086.2020.1831383 -
Journal of the American Academy of... Apr 2022Microneedling as an adjuvant to topical medications has shown promising but variable results in the treatment of melasma. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Microneedling as an adjuvant to topical medications has shown promising but variable results in the treatment of melasma.
OBJECTIVE
To conduct a systematic review and meta-analysis on the efficacy of microneedling as an adjuvant to topical therapies for the treatment of melasma.
METHODS
This study followed PRISMA guidelines. All comparative, prospective studies on the use of topical interventions with microneedling for the treatment of melasma were included. Studies involving radiofrequency microneedling were excluded.
RESULTS
Twelve eligible studies comprising 459 patients from 7 different countries were included. Topical therapies included topical tranexamic acid, vitamin C, platelet-rich plasma, non-hydroquinone-based depigmentation serums, and hydroquinone-based depigmenting agents. Topical therapy with microneedling improved melasma severity with a large effect (standardized mean difference >0.8) beyond 8 weeks, with best results seen at 12 weeks. Compared to topical therapy alone, topical therapy with microneedling resulted in an additional improvement in melasma severity with a moderate effect at 8 weeks and a large effect at 12-16 weeks. Microneedling was well tolerated across studies, with no serious adverse events reported.
LIMITATIONS
Heterogeneity in study designs did not allow for a comparison of the efficacy of various topical therapies with microneedling.
CONCLUSION
Microneedling is useful adjuvant to topical therapies for the treatment of melasma.
Topics: Administration, Cutaneous; Ascorbic Acid; Humans; Melanosis; Prospective Studies; Tranexamic Acid; Treatment Outcome
PubMed: 33857549
DOI: 10.1016/j.jaad.2021.03.116 -
The American Journal of Emergency... Jul 2021Acute gastrointestinal bleeding is a common life-threatening emergent condition. Immediate tranexamic acid is useful for reducing hemorrhage following operation and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute gastrointestinal bleeding is a common life-threatening emergent condition. Immediate tranexamic acid is useful for reducing hemorrhage following operation and bleeding trauma, but evidence on the effects of tranexamic acid in patients with gastrointestinal bleeding is limited or highly heterogeneous. It is still unclear about using tranexamic acid in the emergent condition of gastrointestinal bleeding. This study, therefore, aimed to determine whether or not tranexamic acid should be used in gastrointestinal bleeding management through systematic review and meta-analysis.
METHODS
We searched three biomedical databases for relevant randomized controlled trials on this topic. Two authors independently selected studies and extracted data for bias assessment and meta-analysis of bleeding, further intervention, mortality, transfusion, and intensive care unit admission. Available data were pooled using a random-effects model, and the results were presented as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity and small study effects were also assessed.
RESULTS
Thirteen randomized controlled trials (n = 2271) were included in the present synthesis. Our meta-analysis revealed that tranexamic acid significantly reduced the rates of continued bleeding (RR = 0.60; 95%CI, 0.43-0.84), urgent endoscopic intervention (RR = 0.35; 95%CI, 0.24-0.50), and mortality (RR = 0.60; 95%CI, 0.45-0.80) compared with the placebo.
CONCLUSION
According to the available evidence, the present synthesis confirms that tranexamic acid is an effective medication for patients with upper gastrointestinal bleeding. Early administration of tranexamic acid may be worth to be recommended for treating upper gastrointestinal bleeding in the emergency department. However, the effects of tranexamic acid on lower gastrointestinal bleeding warrant further clarification.
Topics: Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 33041136
DOI: 10.1016/j.ajem.2020.08.062