Use of anticoagulants in elderly patients: practical recommendations

Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE) prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF) and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH), unfractionated heparin (UFH) or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA) are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future

A systematic review of biomarkers among hospitalized patients with COVID-19 predictive of venous thromboembolism: A communication from the Predictive and Diagnostic Variables Scientific and Standardization Committee of the ISTH

Background Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures

Risk of neonatal hypothyroidism in newborns from mothers exposed to CTPA during pregnancy: Ancillary data from a prospective outcome study

Background: Neonatal hypothyroidism is often raised as a potential concern for the use of computed tomography pulmonary angiography (CTPA) in pregnant women with suspected pulmonary embolism (PE). Objectives: To assess the incidence of neonatal hypothyroidism among newborns from mothers exposed to CTPA. Patients/methods: Pregnant women with clinically suspected PE were included in a multicenter, multinational prospective diagnostic management outcome study, based on pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb venous compression ultrasonography, and CTPA. Results of Guthrie tests were systematically collected for newborns of all women who required CTPA as part of the diagnostic strategy. A thyroid-stimulating hormone (TSH) level above 15 U/ml was used to define hypothyroidism. Results: Out of the 166 women included in the Swiss participating centers, 149 underwent a CTPA including 14 with twin pregnancies. Eight women suffered a pregnancy loss and results of the Guthrie test could not be retrieved for four newborns. All TSH levels were reported as being below 15 U/ml. The incidence of neonatal hypothyroidism was 0/151 (0.0%, 95% confidence interval: 0.0%-2.5%). Conclusions: We did not identify any cases of neonatal hypothyroidism in our cohort of 149 pregnant women investigated for suspected PE using a CTPA. Along with previous literature data, this provides further reassuring data regarding the use of CTPA in this indication. Keywords: Guthrie test; diagnosis; hypothyroidism; pregnancy; pulmonary embolism

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial.

INTRODUCTION The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial. METHODS Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms. RESULTS Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms. CONCLUSIONS In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial

INTRODUCTION The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial. METHODS Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms. RESULTS Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms. CONCLUSIONS In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms

Challenges and perspectives in the diagnosis of pulmonary embolism in specific populations of patients

Current diagnostic management of patients with suspected pulmonary embolism (PE) relies on diagnostic strategies, rather than an isolated diagnostic test, with sequential assessment of pre-test clinical probability, D-dimer measurement, and – only when needed - thoracic imaging. This work first presents the evolution of PE diagnostic algorithms and challenging issues in specific subgroups of patients. Then, some of our studies contributing to fill knowledge gaps in some subgroups are presented: analysis of the usefulness of D-dimer in patients with renal impairment, prospective validation of diagnostic strategies and assessment of their safety in pregnant patients, assessment of the safety of multidetector CTPA to exclude PE in patients with likely clinical probability. Finally, challenges and future perspectives to overcome concerns about the overuse of CTPA are presented, such as the potential development of PE clinical suspicion rules applicable to all patients with chest symptoms, and the development of alternative less radiating imaging tests

Covid-19, anticoagulation et maladie thromboembolique veineuse : qu’a-t-on appris ?

Severe COVID-19 is associated with venous thromboembolic events and and immuno-thrombotic phenomena, responsible for pulmonary vascular damage. This review summarizes the current knowledge on thrombotic risk in COVID-19 inpatients, the potential predictive factors (including D-dimer) and the randomized trials studying the effect of intermediate or therapeutic-dose anticoagulation on the clinical and thrombotic prognosis. Despite the initial hope, therapeutic anticoagulation does not improve the clinical prognosis in critically ill inpatients, and standard prophylactic anticoagulation is therefore recommended. In non-critical inpatients, the use of therapeutic anticoagulation may help reduce the risk of severe clinical deterioration, but its risk-benefit will be clarified in ongoing studies and meta-analyzes.Le Covid-19 sévère se complique fréquemment d’événements thromboemboliques veineux et de phénomènes d’immunothrombose responsables d’altérations vasculaires pulmonaires. Cet article résume les connaissances actuelles du risque thrombotique lié au Covid-19 hospitalier, les facteurs prédictifs (dont les D-dimères) et les résultats des essais randomisés d’anticoagulation à doses intermédiaire ou thérapeutique. Malgré l’espoir initial, une anticoagulation thérapeutique n’améliore pas le pronostic clinique aux soins intensifs et une anticoagulation prophylactique standard est donc préconisée. En médecine, l’utilisation d’une anticoagulation thérapeutique pourrait contribuer à réduire le risque de détérioration clinique, mais le rapport bénéfice-risque d’une telle stratégie sera précisé dans les résultats des études et méta-analyses en cours

Diagnostic clinique de l’ischémie critique chronique de membre inférieur

Chronic critical ischemia of the lower limb (CCLI) is the most severe form of peripheral arterial disease. This terminology reflects the need to compare treatments based on an accurate and objective description of the clinical cases rather than subjective items like limb threatening ischemia or intervention for limb salvage. At the stage of CCLI the prognosis is very poor with a high risk of major amputation or disability or death. This highlights the importance of a precise clinical evaluation (including an hemodynamic reading of the clinical assessment of the foot) and of the use of the appropriate diagnostic tools to confirms CCLI diagnosis. This approach is invaluable for the correct stratification of the amputation risk

Anticoagulation in the Elderly

Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future

Should we diagnose and treat distal deep vein thrombosis?

Ultrasound series report that isolated distal deep vein thrombosis (DVT), also known as calf DVT, represents up to 50% of all lower-limb DVTs and, therefore, is a frequent medical condition. Unlike proximal DVT and pulmonary embolism, which have been studied extensively and for which management is well standardized, much less is known about the optimal management of isolated calf DVT. Recent data arising from registries and nonrandomized studies have suggested that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. These data had some impact on the international recommendations that recently stated that ultrasound surveillance instead of systematic therapeutic anticoagulation might be an option for selected low-risk patients. However, robust data from randomized studies are scarce. Only 5 randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. The only randomized placebo-controlled trial included low-risk patients (outpatients without cancer or previous venous thromboembolism [VTE]) and was hampered by limited statistical power. Nevertheless, data from this trial confirmed that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE but is associated with a significantly higher risk of bleeding. Further randomized studies are needed to define the best therapy for high-risk patients (inpatients, patients with active cancer, or patients with previous VTE) and the optimal dose and duration of treatment