Venous thromboembolism Khan, Faizan; Tritschler, Tobias; Kahn, Susan R ...
The Lancet (British edition),
07/2021, Letnik:
398, Številka:
10294
Journal Article
Recenzirano
Venous thromboembolism, comprising both deep vein thrombosis and pulmonary embolism, is a chronic illness that affects nearly 10 million people every year worldwide. Strong provoking risk factors for ...venous thromboembolism include major surgery and active cancer, but most events are unprovoked. Diagnosis requires a sequential work-up that combines assessment of clinical pretest probability for venous thromboembolism using a clinical score (eg, Wells score), D-dimer testing, and imaging. Venous thromboembolism can be considered excluded in patients with both a non-high clinical pretest probability and normal D-dimer concentrations. When required, ultrasonography should be done for a suspected deep vein thrombosis and CT or ventilation–perfusion scintigraphy for a suspected pulmonary embolism. Direct oral anticoagulants (DOACs) are the first-line treatment for almost all patients with venous thromboembolism (including those with cancer). After completing 3–6 months of initial treatment, anticoagulation can be discontinued in patients with venous thromboembolism provoked by a major transient risk factor. Patients whose long-term risk of recurrent venous thromboembolism outweighs the long-term risk of major bleeding, such as those with active cancer or men with unprovoked venous thromboembolism, should receive indefinite anticoagulant treatment. Pharmacological venous thromboembolism prophylaxis is generally warranted in patients undergoing major orthopaedic or cancer surgery. Ongoing research is focused on improving diagnostic strategies for suspected deep vein thrombosis, comparing different DOACs, developing safer anticoagulants, and further individualising approaches for the prevention and management of venous thromboembolism.
Objective To prospectively validate the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L; Obesity with body mass index ≥30; or Older age, ≥65 years), which ...states that women with none or one of the criteria can safely discontinue anticoagulants after short term treatment.Design Prospective cohort management study.Setting 44 secondary or tertiary care centres in seven countries.Participants Of 3155 consecutive eligible participants with a first unprovoked venous thromboembolism (VTE, proximal leg deep vein thrombosis or pulmonary embolism) who completed 5-12 months of short term anticoagulant treatment, 370 declined to participate, leaving 2785 enrolled participants. 2.3% were lost to follow-up.Interventions Women with none or one of the HERDOO2 criteria were classified as at low risk of recurrent VTE and discontinued anticoagulants (intervention arm), whereas anticoagulant management for high risk women (≥2 HERDOO2 criteria) and men was left to the discretion of the clinicians and patients (observation arm).Main outcome measure Recurrent symptomatic VTE (independently and blindly adjudicated) over one year of follow-up.Results Of 1213 women, 631 (51.3%) were classified as low risk and 591 discontinued oral anticoagulant treatment. In the primary analysis, 17 low risk women who discontinued anticoagulants developed recurrent VTE during 564 patient years of follow-up (3.0% per patient year, 95% confidence interval 1.8% to 4.8%). In 323 high risk women and men who discontinued anticoagulants, 25 had VTE during 309 patient years of follow-up (8.1%, 5.2% to 11.9%), whereas in 1802 high risk women and men who continued anticoagulants 28 had recurrent VTE during 1758 patient years of follow-up (1.6%, 1.1% to 2.3%).Conclusions Women with a first unprovoked VTE event and none or one of the HERDOO2 criteria have a low risk of recurrent VTE and can safely discontinue anticoagulants after completing short term treatment.Trial registration clinicaltrials.gov NCT00967304.
Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy ...complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.
A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval CI 1.06-2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89-1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80-1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79-1.99) or SGA (OR 1.25, 95% CI 0.92-1.70).
Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors' Summary.
Summary Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These ...complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis. Methods We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate <10th percentile, pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249. Findings We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 14% versus no low-molecular-weight heparin 95/443 (22%) absolute difference −8%, 95% CI −17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36–1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications. Interpretation Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore. Funding Canadian Institutes of Health Research.
AbstractObjectivesTo determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, ...and the cumulative incidence for recurrent VTE up to 10 years.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019).Study selectionRandomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment.Data extraction and synthesisTwo investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity.Results18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%).ConclusionsIn patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE.Systematic review registrationPROSPERO CRD42017056309.
Treatment of Venous Thromboembolism Wells, Philip S; Forgie, Melissa A; Rodger, Marc A
JAMA : the journal of the American Medical Association,
02/2014, Letnik:
311, Številka:
7
Journal Article
Recenzirano
IMPORTANCE Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, potentially lethal condition with acute morbidity. OBJECTIVE To review the ...etiology of VTE and the 3 phases of VTE treatment: acute (first 5-10 days), long-term (from end of acute treatment to 3-6 months), and extended (beyond 3-6 months). EVIDENCE REVIEW Cochrane reviews, meta-analyses, and randomized controlled trials, as well as other clinical trials for topics not covered by the former, were reviewed. Literature searches using broad terms were used to find meta-analyses published in the last 15 years. The ninth edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was used to supplement the literature search. Guidelines from specialty organizations were consulted when relevant. The Canadian Agency for Drugs and Technologies in Health was searched for relevant cost-effectiveness studies. We also searched our own literature database of 8386 articles for relevant research. FINDINGS Low-molecular-weight heparin (LMWH) along with with vitamin K antagonists and the benefits and proven safety of ambulation have allowed for outpatient management of most cases of DVT in the acute phase. Development of new oral anticoagulants further simplifies acute-phase treatment and 2 oral agents can be used as monotherapy, avoiding the need for LMWH. Patients with PE can also be treated in the acute phase as outpatients, a decision dependent on prognosis and severity of PE. Thrombolysis is best reserved for severe VTE; inferior vena cava filters, ideally the retrievable variety, should be used when anticoagulation is contraindicated. In general, DVT and PE patients require 3 months of treatment with anticoagulants, with options including LMWH, vitamin K antagonists, or direct factor Xa or direct factor IIa inhibitors. After this time, decisions for further treatment are based on balancing the risk of VTE recurrence, determined by etiology of the VTE (transient risk factors, unprovoked or malignancy associated), against the risk of major hemorrhage from treatment. Better prediction tools for major hemorrhage are needed. Experience with new oral anticoagulants as acute, long-term, and extended therapy options is limited as yet, but as a class they appear to be safe and effective for all phases of treatment. CONCLUSIONS AND RELEVANCE The mainstay of VTE treatment is anticoagulation, while interventions such as thrombolysis and inferior vena cava filters are reserved for limited circumstances. Multiple therapeutic modes and options exist for VTE treatment with small but nonetheless important differential effects to consider. Anticoagulants will probably always increase bleeding risk, necessitating tailored treatment strategies that must incorporate etiology, risk, benefit, cost, and patient preference. Although great progress has been made, further study to understand individual patient risks is needed to make ideal treatment decisions.
Summary Background Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to ...prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. Methods We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov , number NCT00143598 , and Current Controlled Trials, number ISRCTN71334751. Findings From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. Interpretation ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Funding Canadian Institutes of Health Research.
Case-fatality rates are important for assessing the risks and benefits of anticoagulation in patients with venous thromboembolism (VTE).
To summarize case-fatality rates of recurrent VTE and major ...bleeding events during anticoagulation and recurrent VTE after anticoagulation.
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and all evidence-based medicine reviews in the Ovid interface through the second quarter of 2008.
69 articles (13 prospective cohort studies and 56 randomized, controlled trials) that reported on patients with symptomatic VTE who received anticoagulation therapy for at least 3 months and on the rate of fatal recurrent VTE and fatal major bleeding.
Two reviewers independently extracted data onto standardized forms.
During the initial 3 months of anticoagulation, the rate of recurrent fatal VTE was 0.4% (95% CI, 0.3% to 0.6%), with a case-fatality rate of 11.3% (CI, 8.0% to 15.2%). The rate of fatal major bleeding events was 0.2% (CI, 0.1% to 0.3%), with a case-fatality rate of 11.3% (CI, 7.5% to 15.9%). After anticoagulation, the rate of fatal recurrent VTE was 0.3 per 100 patient-years (CI, 0.1% to 0.4%), with a case-fatality rate of 3.6% (CI, 1.9% to 5.7%).
Estimates come from heterogeneous trial and cohort populations and are not derived from patient-level longitudinal data. Differences in case-fatality rates during and after anticoagulation may be attributable to unmeasured patient characteristics.
The case-fatality rates of recurrent VTE and major bleeding events are similar during the initial period of VTE treatment. The case-fatality rate of recurrent VTE decreases after completion of the initial period of anticoagulation. When combined with absolute rates of recurrent VTE and major bleeding events, case-fatality rates provide clinicians with a surrogate measure of mortality to balance the risks and benefits of anticoagulant therapy in patients with VTE.
Canadian Institute for Health Research and Heart and Stroke Foundation of Ontario.
Bonjour-Hi Welcome to Montréal Kahn, Susan R.; Matino, Davide; Carrier, Marc ...
Journal of thrombosis and haemostasis,
April 2023, 2023-Apr, 2023-04-00, Letnik:
21, Številka:
4
Journal Article
Recenzirano
We invite you to attend International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress from June 24 to 28, 2023, in Montréal, a friendly, reasonably priced multicultural city with an air of ...sophistication and excitement. The ISTH Congress is the most important international meeting in the field of thrombosis, hemostasis, and vascular biology. It offers new research, continuing education, and opportunities to make connections with colleagues from around the world. The theme of ISTH 2023 is “Investing in ISTH’s future: Early career investigators.” Early career investigators have been involved in planning the congress and will be spotlighted in various sessions. The 24 Scientific and Standardization Committee sessions will present ongoing work and the latest research on bleeding and thrombotic disorders. Additional congress highlights include presentations by 4 world-renowned plenary speakers, 28 State-of-the-Art sessions, 80 oral communication sessions, hundreds of poster presentations, and the not-to-be-missed late-breaking trials sessions. See you in Montréal—we cannot wait to welcome you!
Background: Venous thromboembolism (VTE) complicates ∼1.2 of every 1000 deliveries. Despite these low absolute risks, pregnancy-associated VTE is a leading cause of maternal morbidity and mortality.
...Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and others in decisions about the prevention and management of pregnancy-associated VTE.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations.
Results: The panel agreed on 31 recommendations related to the treatment of VTE and superficial vein thrombosis, diagnosis of VTE, and thrombosis prophylaxis.
Conclusions: There was a strong recommendation for low-molecular-weight heparin (LWMH) over unfractionated heparin for acute VTE. Most recommendations were conditional, including those for either twice-per-day or once-per-day LMWH dosing for the treatment of acute VTE and initial outpatient therapy over hospital admission with low-risk acute VTE, as well as against routine anti-factor Xa (FXa) monitoring to guide dosing with LMWH for VTE treatment. There was a strong recommendation (low certainty in evidence) for antepartum anticoagulant prophylaxis with a history of unprovoked or hormonally associated VTE and a conditional recommendation against antepartum anticoagulant prophylaxis with prior VTE associated with a resolved nonhormonal provoking risk factor.
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