(Lancet. 2022;400:1777–1787) Venous thromboembolism (VTE) and subsequent major bleeding are leading causes of maternal morbidity and mortality worldwide, and the risk for recurrence increases for women with a history of VTE. Despite this, evidence-based research on thromboprophylaxis strategies is lacking and the optimal dose of low–molecular-weight heparin (LMWH) thromboprophylaxis during the peripartum and postpartum periods is uncertain. This study aimed to assess the safety and efficacy of low-dose compared to intermediate-dose LMWH for pregnant women with past occurrences of VTE.

strategies used to investigate suspected VTE in postpartum individuals.Future prospective studies should aim to improve the postpartum diagnosis of VTE.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international, multicentre, prospective cohort study in women aged 18-50 diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by Pictorial Blood Loss Assessment Charts (PBAC) at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during three-six month follow-up. AUB was defined as an elevated PBAC score (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and end of follow-up using the Menstrual Bleeding Questionnaire (MBQ). The study was terminated early because of slow recruitment due to the pandemic. Of the 98 women, 65 (66%) met at least one of the three definitions of AUB during follow-up (95% confidence interval (CI) 57-75%). AUB occurred in 60% (36/60) of women without AUB before VTE diagnosis ('new-onset' AUB; 95%CI 47-71%). Overall, QoL decreased over time with a mean MBQ increase of 5.1 points (95%CI 2.2-7.9), but this decrease in QoL was only observed among women with new-onset AUB. To conclude, two out of three women who start anticoagulation for acute VTE suffer from AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies for preventing and treating AUB in this setting. This was an academic study (NCT04748393 at www.clinicaltrials.gov); no funding was received.

La maladie thromboembolique veineuse (MTEV) est la 4e cause de mortalité maternelle dans les pays développés. Selon les recommandations internationales, une prévention de MTEV par héparine de bas poids moléculaire (HBPM) est indiquée pendant la grossesse et les 6 semaines post-partum en cas de haut risque de récidive : antécédents de MTEV non provoquée ou liée à un facteur hormonal. Cependant, ces recommandations ne sont que de faible grade (grade 2B–2C) et laissent le choix entre une dose prophylactique fixe ou une dose plus élevée adaptée au poids, dite dose intermédiaire (environ une demi-dose curative). Connaître les pratiques françaises concernant la prévention secondaire des MTEV chez les femmes enceintes à haut risque de récidive. En février 2014, le Centre d’Investigation Clinique du CHU de Saint-Étienne a envoyé 449 questionnaires à tous les gynéco-obstétriciens (GO) des maternités françaises niveaux 2b ou 3 situées dans 33 villes différentes. Le questionnaire comprenait 3 cas cliniques théoriques de femmes enceintes demandant pour chaque cas si une prescription d’HBPM était nécessaire et si oui, à quelle dose (prophylactique ou intermédiaire). Les antécédents étaient pour le 1er cas une MTEV non provoquée, pour le 2e une MTEV liée aux hormones et pour le 3e une MTEV liée à un facteur de risque (FDR) mineur transitoire. Cent cinq questionnaires ont été complétés (23 %) avec au moins une réponse par ville. En cas d’antécédents de MTEV : – non provoquée, 73 % des GO utiliseraient une HBPM (énoxaparine dans 96 % et tinzaparine dans 4 %) ; 95 % choisiraient une dose prophylactique fixe et 4 % une dose intermédiaire ; – liée aux hormones, 86 % des GO utiliseraient une HBPM (énoxaparine dans 96 % et tinzaparine dans 4 %) ; 84 % choisiraient une dose prophylactique fixe et 12 % une dose intermédiaire ; – liée à un FDR mineur transitoire, 36 % des GO utiliseraient une HBPM (100 % d’énoxaparine) ; 92 % choisiraient une dose prophylactique fixe et 5 % une dose intermédiaire. La majorité des GO français suivent les recommandations malgré leur faible grade et prescrivent des HBPM chez les femmes enceintes aux antécédents de MTEV non provoquée ou liée aux hormones en préférant la dose prophylactique fixe, mais la dose intermédiaire est aussi prescrite. Un essai randomisé comparant l’efficacité et la tolérance de ces doses paraît donc justifié.

To evaluate the efficacy of transcutaneous electrical neurostimulation (TENS) in patients with chronic low back pain (LBP).

BACKGROUND AND OBJECTIVESdespite the numerous publications debating ethical rules of clinical research, older patients' opinions are rarely taken into account. We report on the feelings and memories related by older patients included in a randomised controlled trial.DESIGN AND SETTINGSa closed-questionnaire was submitted to patients, aged >65 years, who had been included in the randomised trial "PREPIC". PREPIC was a multicentre open trial performed in France, that included 400 patients over 42 months. The aim of PREPIC was to evaluate the benefits and risks of prophylactic filter placement in patients with proximal deep-vein thrombosis who were considered to be at risk for pulmonary embolism.RESULTS104 patients (mean age: 74 years) were interviewed. At the time the trial was proposed to them, 45% of patients felt surprised or shocked and 30% feared incurring additional risks. While 85% of patients did not remember the trial methods (including the randomisation), most older patients (77%) not only judged that they received clear medical information but also well remembered (95%) the aim of the study and the treatment they received (67%). Finally, most older patients not only did not regret their participation (91%), but would also recommend their close relations to participate in a clinical trial (62%).CONCLUSIONSthis study demonstrates that medical scientific information can be understood and remembered by older people.

La suspicion de maladie thromboembolique veineuse est une situation frequente et qui pose parfois des problemes diagnostiques difficiles. Pour remplacer la phlebographie et l'angiographie pulmonaire jugees trop invasifs, de nouvelles strategies combinant plusieurs examens non invasifs, tels que le dosage des D-Dimeres, l'echo-doppler veineux des membres inferieurs, la scintigraphie pulmonaire et plus recemment le scanner helicoidal, sont actuellement proposees. Sur le terrain, ces strategies doivent etre adaptees aux conditions locales. La place du scanner spirale par rapport a la scintigraphie pulmonaire reste a preciser dans l'attente de plusieurs grandes etudes internationales. Le diagnostic de l'EP massive requiert une approche tres specifique basee en priorite sur l'utilisation de l'echographie cardiaque. Pour le suivi, la place des examens complementaires (D-Dimeres, echo-doppler veineux, scintigraphie pulmonaire) devrait se developper mais reste a preciser.

Background: Low molecular weight heparins (LMWHs) have become routine thromboprophylaxis in general surgery. However, their actual clinical effect, its magnitude relative to that of unfractionated heparin (UFH), and the optimal dose are still debated.Methods: A meta-analysis was performed of all available randomized trials in general surgery comparing LMWH with placebo or no treatment, or with UFH.Results: Comparison versus placebo or no treatment confirmed that the significant reduction in asymptomatic deep vein thrombosis (DVT) obtained with LMWH (n = 513; relative risk (RR) 0.28 (95 per cent confidence interval 0.14-0.54)) was associated with a significant reduction in clinical pulmonary embolism (n = 5456; RR 0.25 (0.08-0.79)) and clinical venous thromboembolism (VTE) (n = 4890; RR 0.29 (0.11-0.73)), and a trend towards a reduction in overall mortality rate. Comparison versus UFH showed a trend in favour of LMWH, with a significant reduction in clinical VTE (P = 0.049), a trend also found for cancer surgery. LMWH at doses below 3400 anti-Xa units seemed to be as effective as, and safer than, UFH, while higher doses yielded slightly superior efficacy but increased haemorrhagic risk, including that of major haemorrhage.Conclusion: Asymptomatic DVT may be regarded as a reliable surrogate endpoint for clinical outcome in studies investigating thromboprophylaxis in general surgery. LMWH seems to be as effective and safe as UFH. Determination of the optimal dose regimen of LMWH for this indication requires further investigation.

To determine the specificity of pulmonary embolism (PE) symptoms and lung scan perfusion defects in patients with deep vein thrombosis (DVT), we analyzed data on 400 patients with phlebography-proven proximal DVT included in a prospective trial. As the incidence of PE during anticoagulant therapy was the main outcome measure of the trial, all patients underwent lung scanning and/or pulmonary angiography within 48 h of inclusion, and then whenever PE was suspected. Angiography was recommended in patients with nondiagnostic lung scan. At baseline, the presence or absence of PE could be ascertained in 350 patients (87.5%), and 197 (56%) had PE. Sensitivity and specificity of symptoms for PE were 74 and 67%, respectively. Among 37 patients with symptoms and nondiagnostic lung scan, only 8 (22%) had PE at angiography. During anticoagulant therapy (3 mo), there were 29 events suspicious for PE, mostly (53%) within 2 wk of inclusion. Repeated perfusion studies with comparison to baseline tests excluded PE in 21 cases. Cumulated 3-mo risks of suspected and confirmed on-treatment PE were 6.8% (95% CI, 5.4-8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively. even in patients with known proximal DVT, PE symptoms are unspecific and careful imaging studies are needed for diagnosis, both at baseline and during anticoagulant therapy.

Background The prevention of venous thromboembolic disease is less studied in medical patients than in surgery. Methods. We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deep vein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded. Results. Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both casts), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH ( 4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049). Conclusions. This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.

Background-Patients with venous thromboembolism require initial treatment with an immediate-acting anticoagulant, low-molecular-weight heparin. We evaluated a novel synthetic factor Xa inhibitor (SR90107a/ORG31540) as an alternative treatment.Methods and Results-A randomized-parallel-group, phase II trial to assess the efficacy and safety of SR90107a/ORG31540 (5, 7.5, or 10 mg once daily) relative to low-molecular-weight heparin (dalteparin, 100 IU/kg twice daily) in symptomatic proximal deep vein thrombosis. The primary outcome measure was the change in thrombus mass, assessed by ultrasonography of the leg veins and perfusion lung scintigraphy, performed at baseline and day 7+/-1. A positive outcome was defined as improvement of the ultrasound and/or perfusion scan result without deterioration of either test. Other outcome measures included symptomatic, recurrent venous thromboembolism and major bleeding for a period of 3 months. All outcomes were interpreted with the observer unaware of treatment allocation. A positive primary outcome was observed in 46 of 100 (46%), 52 of 108 (48%), 48 of 115 (42%), and 56 of 115 (49%), respectively, of the subjects given 5, 7.5, or 10 mg SR90107a/ORG31540 or dalteparin. There were 8 recurrent thromboembolic complications (2.4%) in the 334 patients treated with SR90107a/ORG31540 and 6 (5.0%) in the 119 dalteparin patients, a difference of 2.6% in favor of SR90107a/ORG31540 (95% CI -2.1% to 10.1%). The incidence of bleeding was low and was similar among the groups.Conclusions-The factor Xa inhibitor SR90107a/ORG31540 appears to be an effective and safe treatment for patients with deep vein thrombosis across a wide range of doses. This synthetic compound merits evaluation in phase III studies.

OBJECTIVE:To compare oral anticoagulant treatment (fluindione) started on either the 1st or the 10th day of a low-molecular-weight heparin (enoxaparin) treatment for deep vein thrombosis confirmed by venography.DESIGN:An open, multicenter, randomized study in two parallel treatment groups.INTERVENTIONS:All patients received enoxaparin, 1 mg/kg s.c. twice daily, and oral fluindione, 20 mg once daily, either beginning on day 1 or on day 10 of the enoxaparin treatment. Enoxaparin was discontinued once the international normalized ratio under fluindione was stable between 2.0 and 3.0 over 2 days. Fluindione treatment was maintained during a 3-month follow-up period.OUTCOME MEASUREMENTS:Specific examinations (venography and/or V/Q lung scanning and/or angiography) were performed only in the event of a clinically suspected recurrence of venous thromboembolism during the 3-month follow-up period. All cases were blindly assessed by an independent Reading Committee.RESULTS:A clinically suspected venous thromboembolism was confirmed by objective tests in 1 of 223 patients (group of delayed introduction of fluindione; n = 111). Equivalence was demonstrated between the two treatment schedules (p < 0.0001) for a maximal difference of 10% (90% confidence interval: -2.42 to 0.58). The mean duration of hospitalization was significantly reduced (p = 0.0001) in the group with early introduction of fluindione. The incidence of hemorrhage was comparable between the two treatment groups.CONCLUSION:Early and delayed introduction of oral anticoagulant treatment in association with subcutaneous enoxaparin in patients with deep vein thrombosis was shown to be equivalent in preventing the recurrence of venous thromboembolism. In patients with early introduction of oral anticoagulant, hospitalization was significantly reduced.

Summary— The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep‐vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice‐daily doses. When the drug effect had been at a steady‐state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups ( P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted ( P = 0.02), but the clinical relevance of factor VII variation at steady‐state is uncertain. In spite of the short pharmacokinetic half‐life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice‐daily administration of acenocoumarol does not appear to be justified.