Suspected recurrent venous thromboembolism (VTE) is a common and vexing clinical problem. Confounding the diagnosis of recurrent VTE is a high frequency of residual VTE from prior VTE. The diagnosis ...of recurrent VTE must be established by comparing current imaging with past imaging to distinguish acute from chronic thrombosis. Next, we must ascertain if non-compliance was the cause of “apparent therapeutic failure” and if non-compliance is at play then re-initiate anticoagulant therapy. Therapeutic failure is relatively uncommon. As such, we must consider underlying causes of therapeutic failures including malignancy and potent thrombophilias. Finally, short term anticoagulant management of therapeutic failures is controversial, and requires further research, but the best current evidence supports a course of full-dose low-molecular-weight heparin (LMWH) (and dose escalated LMWH if failure occurs while on full-dose LMWH).
•Suspected recurrent venous thrombosis is common•First objectively confirm the recurrence then consider the etiology of recurrent VTE and decide whether to change/escalate anticoagulant therapy•Non-compliance is a concern in recurrent VTE
Identifying previously undiagnosed cancer in patients with newly diagnosed venous thromboembolism (VTE) is important. Screening for malignant conditions can potentially diagnose more cases of cancer ...and at earlier stages, thereby preventing cancer-associated morbidity and perhaps mortality.
To summarize the period prevalence of previously undiagnosed cancer at baseline (within 1 month of VTE diagnosis), 6 months, and 12 months after VTE diagnosis and to quantify the additional value of an extensive cancer screening strategy (limited screening plus imaging techniques or tumor marker measurement) at baseline compared with more limited screening (history, physical examination, and simple widely available tests) at baseline.
MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and Evidence-Based Medicine Reviews.
A total of 36 studies that reported the prevalence of undiagnosed cancer at baseline, 6 months, and 12 months were selected. Fourteen articles and 1 abstract also met inclusion criteria for the assessment of extensive versus limited cancer screening.
Two reviewers independently extracted data onto standardized forms.
The period prevalence of previously undiagnosed cancer in patients with unprovoked VTE was 6.1% (95% CI, 5.0% to 7.1%) at baseline and 10.0% (CI, 8.6% to 11.3%) from baseline to 12 months. An extensive screening strategy using computed tomography of the abdomen and pelvis statistically significantly increased the proportion of previously undiagnosed cancer detected from 49.4% (CI, 40.2% to 58.5%) (with limited screening alone) to 69.7% (CI, 61.1% to 77.8%) in patients with unprovoked VTE.
The investigators could not determine complication rates, cost-effectiveness, and difference in morbidity and mortality associated with extensive screening strategies.
Previously undiagnosed cancer is frequent in patients with unprovoked VTE. Many cases of previously undiagnosed cancer are missed by screening. An extensive cancer screening strategy detects more malignant conditions than does a limited screening strategy.
AbstractObjectiveTo determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when warfarin is ...temporarily interrupted for a planned procedure.DesignProspective, double blind, randomised controlled trial.Setting10 thrombosis research sites in Canada and India between February 2007 and March 2016.Participants1471 patients aged 18 years or older with atrial fibrillation or mechanical heart valves who required temporary interruption of warfarin for a procedure.InterventionRandom assignment to dalteparin (n=821; one patient withdrew consent immediately after randomisation) or placebo (n=650) after the procedure.Main outcome measuresMajor thromboembolism (stroke, transient ischaemic attack, proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral embolism, or vascular death) and major bleeding according to the International Society on Thrombosis and Haemostasis criteria within 90 days of the procedure.ResultsThe rate of major thromboembolism within 90 days was 1.2% (eight events in 650 patients) for placebo and 1.0% (eight events in 820 patients) for dalteparin (P=0.64, risk difference −0.3%, 95% confidence interval −1.3 to 0.8). The rate of major bleeding was 2.0% (13 events in 650 patients) for placebo and 1.3% (11 events in 820 patients) for dalteparin (P=0.32, risk difference −0.7, 95% confidence interval −2.0 to 0.7). The results were consistent for the atrial fibrillation and mechanical heart valves groups.ConclusionsIn patients with atrial fibrillation or mechanical heart valves who had warfarin interrupted for a procedure, no significant benefit was found for postoperative dalteparin bridging to prevent major thromboembolism.Trial registrationClinicaltrials.gov NCT00432796.
Unique considerations are needed when diagnosing and treating venous thromboembolism (VTE) in women who are pregnant or postpartum. What are the risks to the fetus, such as drug exposure or the risk ...of radiation with diagnostic imaging? How does the physiology of pregnancy affect imaging techniques and anticoagulation management? How should anticoagulation be managed around labor and delivery? These questions highlight some of the important considerations needed when managing a pregnant patient with suspected or confirmed VTE. This review outlines what is known about the epidemiology, pathophysiology, clinical risk factors, diagnosis, and therapeutic management of VTE in pregnancy. We also review our preferred diagnostic and treatment algorithm for a pregnant patient with suspected or confirmed VTE.
Khan et al provide details on stopping anticoagulation in a woman with unprovoked venous thromboembolism. A previously healthy 47-year-old woman was started on anticoagulant therapy six months ago. ...She had been diagnosed with a submassive pulmonary embolism after returning from a trip to the Caribbean. At that time, she had no associated deep vein thrombosis on ultrasonography and her symptoms have completely resolved without sequelae. She has not had any bleeding while on anticoagulant therapy. She asks about the need to continue anticoagulation, as she is worried about the risk of another pulmonary embolism, but is also concerned about bleeding on anticoagulant therapy. She is wondering if she could take acetylsalicylic acid (ASA) instead. The HERDOO2 rule was applied: the patient's body mass index was 27 kg/m2, she had no postthrombotic syndrome, and her d-dimer level was slightly elevated at 300 g/L. Because the patient had only one of the HERDOO criteria, she was classified as having a low risk of recurrence. After discussion with the patient regarding the long-term bleeding risk associated with anticoagulation, as well as the long-term risk of recurrent venous thromboembolism, a decision was made to stop anticoagulant therapy.
The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain.
To ...determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups.
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021.
Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment.
Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies.
Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs.
Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs.
In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE.
Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).
Long-term low-molecular-weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to ...individual risk of VTE recurrence remains unknown. We performed a retrospective cohort study and a validation study in patients with cancer-associated VTE to derive a clinical prediction rule that stratifies VTE recurrence risk.
The cohort study of 543 patients determined the model with the best classification performance included 4 independent predictors (sex, primary tumor site, stage, and prior VTE) with 100% sensitivity, a wide separation of recurrence rates, 98.1% negative predictive value, and a negative likelihood ratio of 0.16. In this model, the score sum ranged between -3 and 3 score points. Patients with a score ≤ 0 had low risk (≤ 4.5%) for recurrence and patients with a score >1 had a high risk (≥ 19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized, controlled trials comparing low-molecular-weight heparin to coumarin treatment in cancer patients.
By identifying VTE recurrence risk in cancer patients with VTE, we may be able to tailor treatment, improving clinical outcomes while minimizing costs.
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.
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