Summary Pulmonary embolism (PE) is the leading cause of maternal mortality in the developed world. Mortality from PE in pregnancy might be related to challenges in targeting the right population for ...prevention, ensuring that diagnosis is suspected and adequately investigated, and initiating timely and best possible treatment of this disease. Pregnancy is an example of Virchow's triad: hypercoagulability, venous stasis, and vascular damage; together these factors lead to an increased incidence of venous thromboembolism. This disorder is often suspected in pregnant women because some of the physiological changes of pregnancy mimic its signs and symptoms. Despite concerns for fetal teratogenicity and oncogenicity associated with diagnostic testing, and potential adverse effects of pharmacological treatment, an accurate diagnosis of PE and a timely therapeutic intervention are crucial. Appropriate prophylaxis should be weighed against the risk of complications and offered according to risk stratification.
Abstract
Background
Antiphospholipid syndrome is associated with recurrent pregnancy loss. Low-molecular-weight heparin (LMWH) and/or aspirin (ASA) prophylaxis during pregnancy to prevent future ...loss is based on limited trial data with mixed results.
Objectives
Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of LMWH and/or ASA in pregnancy.
Methods
We interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients who had ≥1 late pregnancy loss or ≥2 early losses and persistently positive antiphospholipid antibodies based on the revised Sapporo/Sydney criteria were identified in the a Thrombosis Clinic. Patients were also identified by the TIPPS Study screening logs of excluded patients. Data collection and analysis occurred iteratively, in keeping with constructivist grounded theory methodology.
Results
Our analysis generated three themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) managing high stakes, (2) accepting uncertainty, and (3) focusing on safety. Patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e., using LMWH injections became a “ritual”), whereas physicians reacted by removing themselves from the final decision by “leaving it up to the patient.”
Conclusion
Our findings should be considered when designing future research on studying the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients described potential benefit from the process of taking action, even in the absence of a guaranteed good outcome.
Postpartum venous thromboembolism (VTE) is a leading cause of maternal mortality in developed countries and can carry significant long-term morbidity. Despite being able to identify postpartum VTE ...risk factors in a large proportion of the obstetrical population, there is little high-quality evidence available to guide practice on who should receive postpartum thromboprophylaxis. Based on epidemiological data, women with a prior history of VTE or known potent thrombophilia are likely to benefit from an extended duration of low-molecular-weight heparin (LMWH) prophylaxis. However, significant controversy exists around the benefit and harm of postpartum thromboprophylaxis in women with more modest risk factors, such as those with mild thrombophilias or transient situational risk factors around labor and delivery, such as cesarean delivery. We review the available data for postpartum VTE risk factors and thromboprophylaxis in these patients. This review highlights the latest evidence in the area of postpartum VTE prevention, and is a call to action for further research in this area to improve maternal morbidity and mortality.
•Postpartum women with prior VTE or potent thrombophilia benefit from thromboprophylaxis.•The role of thromboprophylaxis for postpartum women with modest VTE risk factors is unclear.•A call to action for randomized controlled trials and patient-centered research is needed.
The SOX-PTS, Amin, and Méan models are three different clinical prediction scores stratifying the risk for postthrombotic syndrome (PTS) development in patients with acute deep vein thrombosis (DVT) ...of the lower limbs. Herein, we aimed to assess and compare these scores in the same cohort of patients.
We retrospectively applied the three scores in a cohort of 181 patients (196 limbs) who participated in the SAVER pilot trial for an acute DVT. Patients were stratified into PTS risk groups using positivity thresholds for high-risk patients as proposed in the derivation studies. All patients were assessed for PTS 6 months after index DVT using the Villalta scale. We calculated the predictive accuracy for PTS and area under receiver operating characteristic (AUROC) curve for each model.
The Méan model was the most sensitive (sensitivity 87.7%; 95% confidence interval CI: 77.2-94.5) with the highest negative predictive value (87.5%; 95% CI: 76.8-94.4) for PTS. The SOX-PTS was the most specific score (specificity 97.5%; 95% CI: 92.7-99.5) with the highest positive predictive value (72.7%; 95% CI: 39.0-94.0). The SOX-PTS and Méan models performed well for PTS prediction (AUROC: 0.72; 95% CI: 0.65-0.80 and 0.74; 95% CI: 0.67-0.82), whereas the Amin model did not (AUROC: 0.58; 95% CI: 0.49-0.67).
Our data support that the SOX-PTS and Méan models have good accuracy to stratify the risk for PTS.
Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE).
To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients ...with a first unprovoked VTE.
Markov modeling study.
Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events.
Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment.
Lifetime.
Canadian health care public payer.
Indefinite anticoagulation with direct oral anticoagulants.
Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs).
When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person).
Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation.
The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation.
Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE.
Canadian Institutes of Health Research.
The role of aspirin in thromboprophylaxis after total hip arthroplasty (THA) is controversial.
To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous ...thromboembolism (VTE) after THA.
Multicenter randomized, controlled trial with a noninferiority design based on a minimal clinically important difference of 2.0%. Randomization was electronically generated; patients were assigned to a treatment group through a Web-based program. Patients, physicians, study coordinators, health care team members, outcome adjudicators, and data analysts were blinded to interventions. (Current Controlled Trials: ISRCTN11902170).
12 tertiary care orthopedic referral centers in Canada.
778 patients who had elective unilateral THA between 2007 and 2010.
After an initial 10 days of dalteparin prophylaxis after elective THA, patients were randomly assigned to 28 days of dalteparin (n = 400) or aspirin (n = 386).
Symptomatic VTE confirmed by objective testing (primary efficacy outcome) and bleeding.
Five of 398 patients (1.3%) randomly assigned to dalteparin and 1 of 380 (0.3%) randomly assigned to aspirin had VTE (absolute difference, 1.0 percentage point 95% CI, -0.5 to 2.5 percentage points). Aspirin was noninferior (P < 0.001) but not superior (P = 0.22) to dalteparin. Clinically significant bleeding occurred in 5 patients (1.3%) receiving dalteparin and 2 (0.5%) receiving aspirin. The absolute between-group difference in a composite of all VTE and clinically significant bleeding events was 1.7 percentage points (CI, -0.3 to 3.8 percentage points; P = 0.091) in favor of aspirin.
The study was halted prematurely because of difficulty with patient recruitment.
Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days. Given its low cost and greater convenience, aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA.
Canadian Institutes of Health Research.
Abstract
Introduction
The Villalta scale is the endorsed tool to diagnose and grade the severity of postthrombotic syndrome (PTS); however, assessing presence and severity of PTS is time-consuming ...and relies on both the clinician and patient's assessments. The patient-reported Villalta scale version 2 (PRV2) is a visually assisted form that enables patients to self-assess presence and severity of PTS. Herein, we report on external validation of this tool.
Methods
We assessed the agreement and kappa values of PRV2 to diagnose and assess severity of PTS compared with the original Villalta score in a cohort of 181 patients (196 limbs) who participated in the SAVER pilot randomized control trial. Presence of PTS was defined as PRV2 ≥5 or a Villalta score ≥5.
Results
PTS prevalence was 42% using PRV2 and 33% using the Villalta scale. The corresponding kappa and percentage agreement were 0.60 (95% confidence interval CI: 0.49–0.71) and 81% (95% CI: 76–87), respectively. Kappa values and percentage agreements between PRV2 and Villalta scale increased with increasing severity of PTS. The sensitivity of PRV2 to detect PTS of any severity was 84% (95% CI: 73–92) with a specificity of 79% (95% CI: 71–86).
Conclusion
We conclude that the PRV2 is an acceptable tool for diagnosing and grading the severity of PTS.
Post-thrombotic syndrome (PTS) is the most frequent long-term complication of deep vein thrombosis. Apart from anticoagulation, there are no medications, procedures, devices, or lifestyle changes ...that effectively prevent PTS. There is a growing interest in the potential protective effects of statins for the prevention of PTS.
To conduct a systematic review and meta-analysis on the role of statins to prevent PTS after a DVT event.
We searched the MEDLINE(R) ALL, Embase, Cochrane Central Register of Controlled Trials, and Scopus from inception to April 5, 2022. The main concepts searched were “statins” and “post thrombotic syndrome.” There was no language restriction. The main outcome measure was the incidence rate ratio (IRR) for PTS associated with exposure to statins.
Of 1971 screened records, 5 studies were included in the meta-analysis (2 retrospective cohorts and 3 randomized controlled trials RCTs). The pooled incidence of PTS was 34.8% per patient-year (95% CI, 9.5–127.4) in patients receiving a statin and 41.6% per patient-year (95% CI, 13.2–132) in controls. Exposure to statins was associated with a significantly decreased risk of PTS (IRR, 0.78; 95% CI, 0.63–0.96, I2 = 0%). Meta-analysis of the 2 retrospective cohorts found a significant reduction in the risk of developing PTS (IRR, 0.68; 95% CI, 0.51–0.91), whereas meta-analysis of RCTs showed no reduction in PTS occurrence (IRR, 0.92; 95% CI, 0.68–1.25).
Although this systematic review suggests that statins may reduce PTS incidence by 22% after deep vein thrombosis, meta-analysis of RCTs showed no risk reduction. Confirmation of the efficacy of statins on the prevention of PTS should be assessed in larger RCTs.
•Statins may prevent the occurrence of post-thrombotic syndrome (PTS).•We performed a systematic review of 2 observational studies and 3 randomized controlled trials assessing the effect of statins on occurrence of PTS after deep vein thrombosis.•Statins may reduce PTS incidence by 22%, but meta-analysis of randomized controlled trials showed no risk reduction.•Confirmation of the efficacy of statins on the prevention of PTS should be assessed in larger randomized controlled trials.
Objective To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) ...for the secondary prevention of venous thromboembolism. Design Systematic review and network meta-analysis. Data sources Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand. Review methods Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms. Results 12 articles met our inclusion criteria, with 11 999 patients evaluated for efficacy and 12 167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available. Conclusions All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
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