Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366.

Management of isolated distal deep vein thrombosis.

Isolated distal deep vein thrombosis (DVT) represents up to 50% of all lower limb DVT in ultrasound series and is a frequent medical condition, which management is not well established. Data arising from registries and non-randomized studies suggest that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. This data had some impact on international recommendations like the American College of Chest Physicians (ACCP), whose last version stated that ultrasound surveillance might be an option for selected low-risk patients. However, robust data arising from randomized studies are scarce. Indeed, only seven 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. When considering randomized placebo-controlled trials, one included low-risk patients and was hampered by a limited statistical power (CACTUS study). Nevertheless, data from this trial tend to confirm 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 higher risk of bleeding. A second randomized placebo-controlled trial did not assess the necessity of anticoagulant treatment but rather the long-term risk of recurrence and compared 6 weeks versus 12 weeks of treatment with rivaroxaban (RIDTS study). Finally, the last available randomized trial compared a 3-month versus a 12-month edoxaban treatment in patients with cancer and mainly asymptomatic distal DVT, detected by systematic compression ultrasonography. Overall, available data suggest that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE. High risk patients (previous VTE, active cancer, inpatients) might benefit from a course of anticoagulant treatment. However, the optimal anticoagulant intensity and duration are uncertain and further studies are needed.

[Angiology and hemostasis: what's new in 2023]. / Angiologie et hémostase: ce qui a changé en 2023.

We discuss four topics among the angiology and hemostasis studies of importance in 2023. The BASIL-2 study provides new data for the management of chronic limb-threatening ischemia by comparing surgical and endovascular treatment. The new classification of antiphospholipid antibody (aPL) syndrome integrates new clinical elements and gives a different weight among the isotype and titer of aPL. Concizumab, an antibody targeting the tissue factor pathway inhibitor, broadens the therapeutic arsenal for hemophilia A and B as evidenced by the results of the EXPLORER 7 study. The PREVENT-CLOT and CASTING study focus on the prevention of thrombosis after trauma, by testing the role of aspirin or the lack of thromboprophylaxis, respectively.

Parmi les sujets d'angiologie et d'hémostase qui ont marqué l'année 2023, quatre ont retenu notre attention. L'étude BASIL-2 apporte de nouvelles données pour la prise en charge de l'ischémie critique des membres inférieurs en comparant les traitements chirurgical et endovasculaire. La nouvelle classification du syndrome des anticorps antiphospholipides (aPL) intègre de nouveaux items cliniques et donne un poids différent aux isotypes et titres des aPL. Le concizumab, un anticorps ciblant l'inhibiteur de la voie du facteur tissulaire, vient élargir l'arsenal thérapeutique pour les hémophilies A et B comme en témoignent les résultats de l'étude EXPLORER 7. Les études PREVENT-CLOT et CASTING s'intéressent à la prévention de la thrombose après traumatisme, en testant la place de l'aspirine ou l'absence de thromboprophylaxie.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.

BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. LIMITATIONS: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. CONCLUSION: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. PRIMARY FUNDING SOURCE: Dutch Research Council. (PROSPERO: CRD42018089366).

[Anticoagulant treatment in pulmonary embolism : how to initiate and how to pursue ?] / Anticoagulation pour une embolie pulmonaire. Comment l'introduire et la poursuivre?

Pulmonary embolism (PE) is associated with significant morbidity and mortality in the absence of properly prescribed anticoagulant treatment. Direct oral anticoagulants (DOACs) are currently the anticoagulant treatment of first choice. The quality of anticoagulation in the acute phase of PE is a major determinant of patients' prognosis. The dose regimens for the initiation phase must therefore be rigorously respected to ensure the efficacy of the treatment. For the maintenance phase, the reduced doses used in atrial fibrillation are not applicable in venous thromboembolism (VTE) except for edoxaban. Finally, for long-term secondary prevention in patients at risk of VTE recurrence, reduced dose DOACs are currently a very interesting option in terms of benefit-risk balance for the majority of patients.

L'embolie pulmonaire (EP) est associée à une morbimortalité significative en l'absence de traitement anticoagulant bien conduit. Les anticoagulants oraux directs (ACOD) sont actuellement le traitement anticoagulant de 1er choix. La qualité de l'anticoagulation en phase aiguë de l'EP est un facteur déterminant pour le pronostic du patient, les schémas posologiques d'introduction doivent donc être rigoureusement respectés pour assurer la sécurité du traitement. Pour la phase de maintien, les posologies réduites utilisées dans la fibrillation auriculaire ne sont pas valables pour la maladie thromboembolique veineuse (MTEV) hormis pour l'édoxaban. Enfin, pour la prévention secondaire au long cours chez les patients à risque de récidive de MTEV, les ACOD à dose réduite sont actuellement une option très intéressante en termes de balance bénéfice-risque pour une majorité de patients.

Ruling out pulmonary embolism across different healthcare settings: A systematic review and individual patient data meta-analysis.

BACKGROUND: The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. METHODS AND FINDINGS: We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the "failure rate" of each strategy-i.e., the proportion of missed PE among patients categorized as "PE excluded" and "efficiency"-defined as the proportion of patients categorized as "PE excluded" among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. CONCLUSIONS: The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

[Selected highlights in angiology and haemostasis for the year 2021]. / Angiologie-hémostase - Année 2021 : morceaux choisis.

Several topics among those that marked the year 2021 are discussed in this article. Factor XI represents an original target for new anticoagulants, and the first results of a phase 2 study of prophylaxis after knee replacement surgery are very promising. A real-life study confirms that the pulmonary embolism exclusion strategy using an age-adjusted D-dimer cut-off is safe and increases the diagnostic yield. Several studies of tranexamic acid provide further insight into the indications for its use and highlight some potential risks. Finally, the concerns regarding a potential risk of increased mortality related to paclitaxel-eluting technology used in lower limb revascularisation are questioned by the results of the latest trials.

Plusieurs sujets parmi ceux qui ont marqué l'année 2021 sont abordés dans cet article. Le facteur XI représente une cible originale pour de nouveaux anticoagulants et les premiers résultats d'une étude de phase 2 dans la prophylaxie après chirurgie du genou sont très prometteurs. Une étude de vie réelle confirme que la stratégie d'exclusion de l'embolie pulmonaire en utilisant un seuil de D-dimères adapté à l'âge est sûre et augmente le rendement diagnostique. Plusieurs études concernant l'acide tranexamique permettent de mieux cerner les indications de son utilisation et soulignent quelques risques potentiels. Finalement, les données récentes remettent en cause le risque de surmortalité liée à la technologie à élution au paclitaxel utilisée dans les interventions endovasculaires des membres inférieurs rapporté précédemment.

[Hospital mechanical thromboprophylaxis]. / Thromboprophylaxie mécanique hospitalière.

Mechanical thromboprophylaxis is an important part of hospital prevention of venous thromboembolism. It comprises graduated compression stockings and intermittent pneumatic compression. In this review, we summarize its physiological effect on venous hemodynamics, recent clinical studies that offer contrasting results, and discuss its utility in contemporary clinical practice. Mechanical thromboprophylaxis is currently suggested in patients at high thrombotic and hemorrhagic risk, favoring intermittent pneumatic compression, but does not seem useful in addition to pharmacological thromboprophylaxis.

La thromboprophylaxie mécanique est une composante importante de la prévention hospitalière de la maladie thromboembolique veineuse. Elle comprend la compression graduée par bas ou chaussettes et la compression pneumatique intermittente (CPIn). Dans cet article, nous résumons son effet veineux physiologique et revenons sur les études cliniques récentes qui offrent des résultats contrastés. Enfin, nous discutons de sa place en clinique contemporaine. La thromboprophylaxie mécanique est actuellement suggérée chez des patients à hauts risques thrombotique et hémorragique, en privilégiant la compression pneumatique intermittente, mais ne semble pas utile en plus d'une thromboprophylaxie pharmacologique.

[Hemodynamic and cardiovascular implications of arteriovenous fistulas in hemodialysis]. / Répercussions hémodynamiques et cardiovasculaires des fistules artérioveineuses en hémodialyse.

Arteriovenous fistula (AVF) remains the vascular access of choice in hemodialysis but generates cardiovascular constraints. Its creation immediately induces an increase in cardiac output. Increased venous return and subsequent volume overload lead to biventricular remodeling, and eventually to dysfunction. High-output heart failure (HOHF) caused by high-flow AVF is a recognized but not strictly defined clinical entity, based on the combination of hypervolemia with an elevated cardiac output. A Qa greater than 2 L/min is a risk factor for HOHF, particularly in susceptible patients. The most used flow reduction procedure is post-anastomotic vein caliber reduction by a banding technique, relieving symptoms and partially reversing previously induced structural abnormalities, but the benefit often remains limited in time.

La fistule artérioveineuse (FAV) demeure l'accès vasculaire de choix en hémodialyse mais engendre des contraintes cardiovasculaires. Sa création génère une élévation du débit cardiaque. L'augmentation du retour veineux puis la surcharge en volume induisent un remodelage biventriculaire pouvant mener à une dysfonction. L'insuffisance cardiaque à haut débit (ICHD) causée par un hyperdébit de la FAV est une entité clinique connue mais pas strictement définie, reposant sur une hypervolémie et une élévation du débit cardiaque. Un débit d'accès supérieur à 2 l/min est un facteur de risque d'ICHD, en particulier chez des patients susceptibles. Une intervention possible de réduction de débit est la réduction du calibre de la veine post-anastomotique par cerclage, soulageant les symptômes et inversant partiellement les anomalies structurelles induites mais a souvent un effet transitoire.

Proximal deep vein thrombosis and pulmonary embolism in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: COVID-19 appears to be associated with a high risk of venous thromboembolism (VTE). We aimed to systematically review and meta-analyze the risk of clinically relevant VTE in patients hospitalized for COVID-19. METHODS: This meta-analysis included original articles in English published from January 1st, 2020 to June 15th, 2020 in Pubmed/MEDLINE, Embase, Web of science, and Cochrane. Outcomes were major VTE, defined as any objectively diagnosed pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT). Primary analysis estimated the risk of VTE, stratified by acutely and critically ill inpatients. Secondary analyses explored the separate risk of proximal DVT and of PE; the risk of major VTE stratified by screening and by type of anticoagulation. RESULTS: In 33 studies (n = 4009 inpatients) with heterogeneous thrombotic risk factors, VTE incidence was 9% (95%CI 5-13%, I2 = 92.5) overall, and 21% (95%CI 14-28%, I2 = 87.6%) for patients hospitalized in the ICU. Proximal lower limb DVT incidence was 3% (95%CI 1-5%, I2 = 87.0%) and 8% (95%CI 3-14%, I2 = 87.6%), respectively. PE incidence was 8% (95%CI 4-13%, I2 = 92.1%) and 17% (95%CI 11-25%, I2 = 89.3%), respectively. Screening and absence of anticoagulation were associated with a higher VTE incidence. When restricting to medically ill inpatients, the VTE incidence was 2% (95%CI 0-6%). CONCLUSIONS: The risk of major VTE among COVID-19 inpatients is high but varies greatly with severity of the disease. These findings reinforce the need for the use of thromboprophylaxis in all COVID-19 inpatients and for clinical trials testing different thromboprophylaxis regimens in subgroups of COVID-19 inpatients. TRIAL REGISTRATION: The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews ( CRD42020193369 ).

[COVID-19, anticoagulation and venous thromboembolism: what have we learned ?] / 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.

[Towards new indications for direct oral anticoagulants]. / Angiologie-hémostase - Vers de nouvelles indications des anticoagulants oraux directs.

Direct oral anticoagulants (DOAC) represent commonly prescribed drugs in everyday clinical practice for indications such as atrial fibrillation, prevention of venous thromboembolic disease (VTE) after major orthopaedic surgery, treatment of deep vein thrombosis and pulmonary embolism, and long term prevention of VTE recurrence. More recently, the efficacy of DOAC has been demonstrated in new clinical situations, such as heparin-induced thrombocytopenia, cancer-associated VTE and secondary prevention of cardiovascular events in patients with atherothrombotic arterial disease. This article's aims is to present the recent data on which these new indications are based.

Les anticoagulants oraux directs (ACOD) font actuellement partie des médicaments couramment prescrits en pratique clinique dans les indications telles que la fibrillation atriale, la prévention de la maladie thromboembolique veineuse (MTEV) après chirurgie orthopédique majeure, le traitement de la thrombose veineuse profonde et embolie pulmonaire et la prévention de la récidive de MTEV au long cours. Se sont récemment rajoutées de nouvelles situations cliniques dans lesquelles les ACOD ont fait la preuve de leur efficacité, telles que la thrombopénie induite par l'héparine, le traitement de la MTEV liée au cancer et la prévention secondaire des événements cardiovasculaires chez les patients avec maladie athéromateuse. Cet article a pour but de présenter les données récentes sur lesquelles sont basées ces nouvelles indications.

[Diagnosis and management of pulmonary embolism : some reflections on the latest ESC guidelines]. / Diagnostic et prise en charge de l'embolie pulmonaire - Quelques réflexions sur les dernières recommandations de l'European Society of Cardiology.

The latest recommendations from the European Society of Cardiology (ESC) on the diagnostic and therapeutic management of pulmonary embolism (PE) published this year provide an important update compared to the 2014 version. In terms of diagnosis, the use of the age-adjusted D-dimer cutoff is currently suggested, and a diagnostic algorithm for suspected PE during pregnancy is proposed. Detailed recommendations are provided for the initial orientation of patients with acute PE based on prognostic stratification criteria, as well as for clinical follow-up after PE. Finally, direct oral anticoagulants are included as therapeutic options for the treatment of cancer-associated thrombosis.

Les dernières recommandations de l'European Society of Cardiology sur la prise en charge diagnostique et thérapeutique de l'embolie pulmonaire (EP) publiées cette année apportent une mise à jour importante par rapport à la version 2014. Au niveau du diagnostic, l'adaptation du seuil de D-dimères à l'âge du patient est actuellement suggérée, et un algorithme diagnostique durant la grossesse est proposé. Des recommandations détaillées quant à l'orientation initiale des patients avec EP aiguë sont exposées en fonction de critères de stratification pronostique, de même que pour le suivi clinique après EP. Enfin, sur la base des dernières données à disposition, les anticoagulants oraux directs sont intégrés dans l'arsenal thérapeutique du traitement des thromboses associées au cancer.

[Digital ischemia: a diagnostic challenge]. / L'ischémie digitale : un défi diagnostique.

Digital ischemia is suspected in presence of a cold, pale or cyanotic and painful finger. It is a diagnostic and therapeutic emergency and needs urgent referral to a vascular specialist. Digital pressure measurement is needed to confirm the diagnosis. A thorough history taking and physical examination help to guide patients' management. Antithrombotic therapy - with an antiplatelet or anticoagulant drug depending on the most likely etiology - need to be introduced without delay, while awaiting the results of the individualized etiologic workup. Hospital admission is often necessary. A prompt diagnostic and therapeutic management allows satisfactory pain control and avoidance of irreversible digital lesions in the majority of cases.

L'ischémie digitale est évoquée devant une froideur, pâleur ou cyanose, et une douleur digitale accompagnées ou non d'une plaie. Il s'agit d'une urgence diagnostique et thérapeutique nécessitant un avis spécialisé. Une mesure des pressions digitales est nécessaire pour confirmer le diagnostic. Un interrogatoire et un examen clinique minutieux permettent d'orienter la prise en charge. Un traitement antithrombotique ­ antiplaquettaire ou anticoagulant en fonction de la présomption clinique ­ doit être introduit sans délai, en attendant le résultat du bilan étiologique, qui sera affiné de façon individuelle. Une hospitalisation est souvent nécessaire. L'instauration rapide de la prise en charge permet de soulager la douleur et d'éviter la progression vers des lésions irréversibles.

[Evolution of thromboprophylaxis after hip and knee arthroplasties]. / Évolution de la thromboprophylaxie après prothèses de hanche et de genou.

Venous thrombotic events frequently complicate major elective arthroplasties such as hip and knee replacements. The risk of proximal deep vein thrombosis and pulmonary embolism is estimated at 5 %. For decades, the use of low-dose heparins for up to 5 weeks post-surgery has helped to reduce the risk of thrombotic complications. In this narrative review, we describe the evidence supporting the use of direct oral anticoagulants (in Switzerland - rivaroxaban and apixaban), whose risk-benefit ratios appears superior to that of heparins, at a lower cost. Hybrid strategies combining a short-term anticoagulant followed by low-dose aspirin are also recommended for patients deemed at low thrombotic risk.

Les thromboses veineuses profondes proximales et les embolies pulmonaires sont des complications redoutées après des interventions électives majeures en chirurgie orthopédique (prothèses totales de la hanche et du genou), avec une incidence cumulée estimée à 5 %. Depuis des décennies, ce risque est réduit par l'utilisation d'héparine à dose préventive jusqu'à 5 semaines postopératoires. Dans cette revue narrative, nous décrivons les évidences motivant l'utilisation des anticoagulants oraux directs (rivaroxaban et apixaban en Suisse) qui semblent présenter un rapport bénéfice-risque supérieur aux héparines, à un coût moindre. Des stratégies hybrides comprenant un anticoagulant puis l'aspirine sont désormais également recommandées chez des patients considérés à bas risque thrombotique.

[Venous thrombotic risk related to SARS-CoV-2†: prevalence, recommendations and perspectives]. / Risque thrombotique veineux induit par le SARS-CoV-2†: prévalence, recommandations et perspectives.

Since the SARS-CoV-2 pandemic outbreak, growing evidence suggests that patients suffering from COVID-19 are at increased risk of thrombotic events. The sepsis-related activation of the coagulation combined with a high prevalence of common thrombotic risk factors could contribute to this prothrombotic state. Coagulation biomarkers could help in the identification of patients at risk of complications and mortality. The incidence of venous thromboembolic events appears to be increased, especially in severe COVID-19 patients. Based on that knowledge, several societies have provided recommendation on the prevention of venous thromboembolism. In this narrative review, we summarize available epidemiologic data on venous thromboembolism and recommendations on thromboprophylaxis in COVID-19.

Depuis le début de l'épidémie de SARS-CoV-2, des faisceaux d'évidences suggèrent que les patients souffrant de COVID-19 sont à risque augmenté d'événements thrombotiques. L'activation de la coagulation secondaire au sepsis associée à des facteurs de risques thrombotiques classiques pourrait contribuer à cet état prothrombotique. Les marqueurs de la coagulation semblent stratifier le risque de détérioration clinique et de mortalité. Le risque de la maladie thromboembolique veineuse (MTEV) semble très élevé, notamment chez les patients sévèrement atteints. Dans ce contexte, de nombreuses sociétés savantes ont émis des recommandations pour la prévention de la MTEV. Nous proposons une mise à jour des connaissances actuelles sur les données épidémiologiques disponibles et sur les recommandations pour la prévention de la MTEV dans le COVID-19.

Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study.

Background: Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. Objective: To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Design: Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). Setting: 11 centers in France and Switzerland between August 2008 and July 2016. Patients: Pregnant women with clinically suspected PE in emergency departments. Intervention: Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months. Measurements: The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up. Results: 441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n = 7], positive CTPA result [n = 19], and high-probability V/Q scan [n = 2]) and excluded in 367 (clinical probability and negative D-dimer result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up. Limitation: There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE. Conclusion: A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women. Primary Funding Source: Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.

Multiple arteriovenous malformations caused by RASA1 gene mutation presenting during pregnancy - a case report and review of the literature.

Pregnancy can influence the development and progression of congenital arteriovenous malformations (AVM) and thus lead to life-threatening complications for the mother and fetus like high output cardiac failure and premature delivery. The simultaneous presence of a capillary malformation and AVM strongly suggests a RASA1 related disorder. Keywords: Arteriovenous malformations, capillary malformation-arteriovenous malformation, capillaries/abnormalities, port-wine stain, pregnancy, RASA1 protein.

[Direct oral anticoagulants in the treatment of cancer-associated thrombosis]. / Anticoagulants oraux directs dans le traitement des événements thrombo­emboliques veineux liés au cancer.

The use of direct oral anticoagulants (DOACs) has been largely -implemented in the management of venous thromboembolic disease in non-cancer patients. In cancer-associated thrombosis, low molecular weight heparins (LMWHs) and especially dalteparin have long been the reference standard therapy. Following the publication of two randomised trials comparing edoxaban and rivaroxaban to -dalteparin, DOACs now represent an alternative with an interesting efficacy and safety profile. Moreover, they offer the comfort of an oral administration and a lower cost. In patients with gastrointestinal or genitourinary cancers however, a higher bleeding risk has been shown with DOACs. LMWHs thus remain the treatment of choice in this group of patients.

L'utilisation des anticoagulants oraux directs (ACOD) pour le traitement de la maladie thromboembolique veineuse (MTEV) chez les patients sans cancer est déjà largement implémentée. En cas de MTEV liée au cancer, les héparines de bas poids moléculaire (HBPM) et en particulier la daltéparine, ont longtemps ­représenté le traitement de référence. Suite à la publication de deux études randomisées récentes comparant l'édoxaban et le rivaroxaban à la daltéparine, les ACOD se sont révélés être une alternative efficace, avec un profil de sécurité satisfaisant, ­offrant par ailleurs le confort d'une administration orale et un coût moindre. Toutefois, en raison d'un risque hémorragique ­accru sous ACOD chez les patients avec un cancer de localisation digestive ou urogénitale, les HBPM restent le traitement de choix dans ce groupe de patients.

[Unprovoked venous thromboembolism : should we look for occult cancer ?] / Maladie thromboembolique veineuse idiopathique : faut-il rechercher un cancer occulte?

Idiopathic venous thromboembolic disease may be the first manifestation of a cancer yet undiagnosed. Early detection of neoplasia may allow a timely management and a reduction of mortality. However, the nature and extent of screening for hidden cancer is still debated. The purpose of this article is to review the usefulness of occult cancer screening in patients with idiopathic venous thromboembolism.

La maladie thromboembolique veineuse idiopathique peut être la première manifestation d'un cancer non encore diagnostiqué. La découverte précoce d'une néoplasie pourrait permettre une prise en charge plus rapide, et ainsi en réduire potentiellement la mortalité. Cependant, à l'heure actuelle, la nature et l'exhaustivité du dépistage à la recherche d'un cancer occulte chez ce groupe de patients restent encore débattues. L'objectif de cet article est de faire le point sur l'utilité du dépistage de cancer occulte en cas de maladie thromboembolique veineuse idiopathique.