Search

International audience; Background: Bleeding during oral anticoagulant therapy is currently codified by expert guidelines. Monitoring of coagulation during bleeding events is challenging. Our study sought to assess thrombin generation assay (TGA) in direct oral anticoagulant-treated patients without bleeding (WB), bleeding without reversal therapy (BR-), and bleeding with reversal therapy (BR+).Methods: We conducted a prospective, monocentric study from June 2015 to June 2018. For all bleeding groups, TGA was evaluated using platelet-poor plasma collected upon arrival at emergency (T0), and 30 min (T1), 6 h (T2) and 24 h (T3) after reversal therapy (if indicated) following activation by tissue factor 5 pM and phospholipids.Results: Overall, 292 patients participated, including 91 BR+, 94 BR-, and 107 WB patients. At T0, vitamin K antagonist reversed (VKA-BR+) patients experienced a significant decrease in TGA parameters (ETP and peak) compared with VKA without bleeding (VKA-WB). Compared with healthy controls, VKA-BR+ patients reversed by four-factor prothrombin complex concentrate (4F-PCC) displayed comparable TGA 's ETP and peak at T1, T2, and T3, whereas direct anti-Xa BR+ patients reversed by 4F-PCC or activated prothrombin complex concentrate (aPCC) reached thrombin generation parameters that exceeded normal range at T2 and T3.Conclusions: In VKA-treated patients reversed by 4F-PCC, TGA parameters were normalized, whereas in rivar-oxaban or apixaban-treated patients reversed by 4F-PCC or aPCC, TGA parameters exceeded normal range. Further studies are needed to compare the efficacy and safety of a different dose of reversal therapy and the impact on coagulation parameters.

Supplemental material, sj-docx-1-his-10.1177_11786329231174340 for The Association Between Age and Admission to an Inappropriate Ward: A Cross-Sectional Survey in France by Diane Naouri, Henri Panjo, Laura Moïsi, Carlos El Khoury, Patrice Serre, Jeannot Schmidt, Youri Yordanov and Nathalie Pelletier-Fleury in Health Services Insights

International audience; 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.

Contexte. L’encombrement des services d’accueil des urgences (SAU) est au coeur de l’actualité. Cette saturation crée de multiples insatisfactions pour les usagers et pour le personnel médical. Une des causes évoquées est la présence de consultations jugées inappropriées par les SAU. Objectif. Explorer les motivations des patients consultant au SAU pour des motifs relevant d’une consultation de médecine générale. Méthode. Étude qualitative avec analyse inductive générale réalisée en 2017 par des entretiens semi-dirigés auprès de 76 patients adultes consultant au SAU pour des motifs de médecine générale pendant les horaires de permanence de soins. Résultats. La définition de l’urgence pour les patients était complexe. La traumatologie au SAU faisait l’unanimité. Ils élargissaient la définition de l’urgence avec l’absence d’alternatives médicales. La motivation principale de consultation au SAU était la facilité d’accès aux soins et la facilité organisationnelle. L’offre de soins en ambulatoire ne permettait pas de répondre à la demande des patients. Les patients étaient conscients que l’encombrement des SAU était responsable d’un temps d’attente plus long. Ils l’expliquaient par un manque de personnels au SAU et par un excès de consultations jugées inappropriées. Conclusion. Les patients ne définissaient plus l’urgence comme une urgence réelle ou ressentie, mais comme une nécessité de consulter immédiatement pour avoir des réponses rapides à leur problème de santé. Notre système de soins doit être réorganisé.

Additional file 2. Examples of Multiple Choice Questions.

Additional file 1. List of lectures.

Additional file 3. Timing of the study (Figure). Legend: THM, take-home message; MCQ: multiple choice question.

BACKGROUND: Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. METHODS: We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin). RESULTS: Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage. CONCLUSIONS: In patients with acute major bleeding associated with the use of a factor Xa in-hibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 .)

Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. Results The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. Conclusions On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .)

Background Suspected pulmonary embolism (PE) is a frequent, complex and harmful situation. In a cohort study conducted in 117 emergency departments, we observed that diagnostic management was inappropriate according to international guidelines in the majority of the patients. The risk for thromboembolism during follow-up in patients left untreated (ie, false negative risk) was sixfold higher in these patients than in those who received appropriate management. Of note, proper management was found to be hampered in institutions that lacked a written diagnostic algorithm.1 We initiated the SPEED program with the aim of improving diagnostic decision making for PE. Because paper guidelines dissemination has generally little effect, we thought to use a computerised clinical decision support system (CDSS). The SPEED program CDSS development We developed a CDSS software for handheld computers named SPEED. It is based on Bayesian principles and a dynamic calculation of PE probability. Using clinical probability estimation and the likelihood ratios of the diagnostic tests, SPEED guides diagnostic decision making step by step until the risk of error is low enough to rule-out or to rule-in PE with confidence.2 CDSS assessment We assessed its effectiveness in a cluster-randomised trial involving 20 emergency departments provided with handheld computers. After a preintervention period with baseline testing assessment, the centers were randomly assigned to activation of the CDSS on the devices or posters and pocket cards that showed validated diagnostic strategies. Results A greater proportion of patients in both groups received appropriate diagnostic testing during the intervention period than in the preintervention period; however, the increase was of significantly greater in the CDSS group (+30.2% vs +10.9%, p=0.023). Patients had fewer tests in the CDSS group than in the paper guidelines group to achieve appropriate work-up. During intervention period, the frequency of venous thromboembolic events in patients who were untreated because of a negative initial work-up was low in the two groups (1% vs 1.5%) but notably lower than in the observational study performed 2.5 years earlier (4.7%).13 Discussion Distributing guidelines for diagnosing PE and especially using a CDSS on handheld devices improves diagnostic decision-making in emergency departments. Moreover, our results suggest a clinical impact of the quality improvement with less thromboembolic events during follow-up. The CDSS SPEED is now distributed free of charge on www.thrombus.fr. Versions for other devices are under construction. A continual impact assessment in routine clinical practice is planned for French users. Contexte La suspicion d9embolie pulmonaire (EP) est une situation frequente, complexe et potentiellement grave. Dans une etude observationnelle conduite dans 117 services d9urgence, nous avons constate que la demarche diagnostique lors d9une suspicion d9EP etait non conforme aux recommandations internationales environ une fois sur 2. Chez les patients pour lesquels l9hypothese d9une EP n’etait pas retenue, le risque de survenue d9un evenement thromboembolique dans les 3 mois (ie, risque de faux negatifs), etait 6 fois plus important lorsque la demarche etait non conforme que lorsqu9elle etait conforme.1 Ces constations et le fait que les demarches diagnostiques etaient plus souvent conformes dans les centres ayant un protocole operationnel, nous ont conduit a mettre en place le programme SPEED avec pour but d9ameliorer les pratiques diagnostiques par une aide informatisee a la decision. Le programme SPEED Elaboration de l9outil d9aide a la decision Nous avons elabore un logiciel d9aide a la decision fonctionnant sur ordinateurs de poche et s9appuyant sur une mesure dynamique de la probabilite diagnostique a partir de la probabilite clinique et des rapports de vraisemblance des tests selon les principes de Bayes.2 SPEED guide le clinicien pas a pas afin qu9il determine la probabilite clinique et choisisse le test ou les tests appropries jusqu’a ce que le risque d9erreur soit suffisamment faible pour qu9il puisse prendre une decision fiable. Evaluation de l9outil d9aide a la decision Nous avons evalue l9interet du logiciel SPEED par comparaison a des recommandations ecrites dans le cadre d9une etude prospective randomisee par centre. Vingt services d9urgences ont recus des ordinateurs de poches pour consigner les demarches realisees chez les patients suspects d9EP. Apres une phase d’evaluation passive, ils ont ete randomises en 2 groupes : aide informatisee a la decision sur les ordinateurs de poches ou recommandations ecrites sur affiches et fiches de poche. Resultats Les deux interventions ont entraine une augmentation significative du taux de demarches appropriees par comparaison a la periode d’evaluation passive. Cependant, l9augmentation a ete significativement plus importante avec l9aide informatisee qu9avec les recommandations ecrites (+30.2% vs +10,9% ; p=0.023). Moins de tests diagnostiques ont ete realises pour obtenir une decision appropriee avec le logiciel SPEED qu9avec les recommandations ecrites (1.76 vs 2.25; p Discussion et perspectives Nos resultats demontrent l9efficacite de la diffusion de recommandations et particulierement de l9aide informatisee a la decision sur la qualite des pratiques diagnostiques lors des suspicions d9EP aux urgences et suggere un impact clinique par une moindre frequence des accidents thomboemboliques dans le suivi. Le logiciel SPEED est distribue gratuitement sur le site www.thrombus.fr. Des evolutions sont prevues afin qu9il puisse fonctionner quelque soit le support informatique et en differentes langues. Une evaluation continue de son impact en pratique quotidienne est envisagee dans le cadre d9un groupe d9utilisateurs realisant une evaluation des pratiques professionnelles.