Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: comparison of 40 mg o.d. vs 40 mg b.i.d. The X-COVID19 Randomized Clinical Trial

It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards. This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. vs 40 mg o.d. enoxaparin in COVID-19 patients, between April 30, 2020 and April 25, 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (Sto arrivando! 6.5, 95% CI, 1.5-11.6). Absence of concomitant DVT and imaging characteristics suggest that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically non-significant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. In conclusion, no DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

Cost-effectiveness of early placement of vena cava filters to prevent symptomatic pulmonary embolism in patients with contraindications to prophylactic anticoagulant

Introduction: Vena cava filters have been used as a primary means to prevent symptomatic pulmonary embolism (PE) in trauma patients who cannot be anticoagulated after severe injury, but the economic implications for this practice remain unclear. Methods: Using a healthcare system perspective to analyze the a priori primary outcome of the da Vinci trial, we report the cost-effectiveness of using vena cava filters as a primary means to prevent PE in patients who have contraindications to prophylactic anticoagulation after major trauma. Results: Of the 240 patients enrolled, complete, prospectively collected, hospital cost data during the entire hospital stay − including costs for the filter, medical/nursing/allied health staff, medical supplies, pathology tests, and radiological imaging − were available in 223 patients (93%). Patients allocated to the filter group ( n = 114) were associated with a reduced risk of PE (0.9%) compared to those in the control group ( n = 109, 5.5%; p = 0.048); and the filter’s benefit was more pronounced among those who could not be anticoagulated within 7 days (filter: 0% vs control: 16%, Bonferroni-corrected p = 0.02). Overall, the cost needed to prevent one PE was high (AUD $379,760), but among those who could not be anticoagulated within 7 days, the costs to prevent one PE (AUD $36,156; ~ USD $26,032) and gain one quality-adjusted life-year (AUD $30,903; ~ USD $22,250) were substantially lower. Conclusion: The cost of using a vena cava filter to prevent PE for those who have contraindications to prophylactic anticoagulation within 3 days of injury is prohibitive, unless such contraindications remain for longer than 7 days. (Australian New Zealand Clinical Trials Registry no.: ACTRN12614000963628)

Rivaroxaban for the prevention of venous thromboembolism after radiofrequency ablation of saphenous veins concomitant with miniphlebectomy, sclerotherapy, or no treatment of varicose tributaries

Objective To assess the efficacy and safety of once-daily 10 mg rivaroxaban for venous thromboembolism prophylaxis after ClosureFast radiofrequency ablation (RFA) of saphenous veins. Method The medical records of patients, who had a Caprini score of ≥3, underwent RFA, received prophylactic rivaroxaban for five days, and completed follow up at one month were reviewed for efficacy (a combination of endovenous heat-induced thrombosis [EHIT] grade of 2–4, any symptomatic or asymptomatic deep vein thrombosis [DVT], and symptomatic pulmonary embolism [PE]) and safety (a combination of major and clinically relevant non-major [CRNM] bleeding) outcomes. Results The results of RFA for 248 great saphenous and 24 small saphenous veins with the concomitant miniphlebectomy (63.8%) and sclerotherapy (16.5%) were analyzed. The primary efficacy outcome occurred in 5 of 218 (2.3%; 95%CI, 1.0–5.3%) patients: three EHITs and two symptomatic DVTs. The CRNM bleeding was reported in two patients (0.9%; 95% CI, 0.2–3.3%). No difference was observed in comparison with 79 similar patients who received 40 mg of subcutaneous enoxaparin during the same time period. Conclusion Once-daily 10 mg rivaroxaban is suitable for VTE prophylaxis after RFA of saphenous veins.

STOP leg clots—Swedish multicentre trial of outpatient prevention of leg clots: study protocol for a randomised controlled trial on the efficacy of intermittent pneumatic compression on venous thromboembolism in lower leg immobilised patients

IntroductionLeg immobilisation in a cast or an orthosis after lower limb injuries is associated with a high risk of complications of venous thromboembolism (VTE) and hampered healing. Current pharmacoprophylaxes of VTE are inefficient and associated with adverse events. Intermittent pneumatic compression (IPC) could represent a novel, efficient and safe VTE-prophylactic alternative that may enhance injury healing. The aim of STOP leg clots is to assess the efficacy of adjuvant IPC-therapy on reduction of VTE incidence and improvement of healing in lower leg immobilised outpatients.Methods and analysisSTOP leg clots is a multicentre randomised controlled superiority trial. Eligible patients (700 patients/arm) with either an acute ankle fracture or Achilles tendon rupture will be randomised to either addition of IPC during lower-leg immobilisation or to treatment-as-usual. The primary outcome will be the total VTE incidence, that is, symptomatic and asymptomatic deep venous thrombosis (DVT) or symptomatic pulmonary embolism (PE), during the leg immobilisation period, approximately 6–8 weeks. DVT incidence will be assessed by screening whole leg compression duplex ultrasound at removal of leg immobilisation and/or clinically diagnosed within the time of immobilisation. Symptomatic PE will be verified by CT.Secondary outcomes will include patient-reported outcome using validated questionnaires, healing evaluated by measurements of tendon callus production and changes in VTE-prophylactic mechanisms assessed by blood flow and fibrinolysis. Data analyses will be blinded and based on the intention-to-treat.Ethics and disseminationEthical approval was obtained by the ethical review board in Stockholm, Sweden, Dnr 2016/1573-31. The study will be conducted in accordance with the Helsinki declaration. The results of the study will be disseminated in peer-reviewed international journals.Trial registrationNCT03259204.Time schedule1 September 2018 to 31 December 2022

Bilateral pulmonary embolism without deep venous thrombosis was observed after knee arthroscopy: a case report

Background Symptomatic pulmonary embolism (PE) after knee arthroscopy is extremely rare. If the embolism is not treated promptly, the patient may die. Bilateral pulmonary embolism with associated pulmonary infarct without concomitant deep vein thrombosis has never been reported following routine knee arthroscopy. Case presentation A 50-year-old female patient with no other risk factors other than hypertension, obesity, varicose veins in the ipsilateral lower extremities and elevated triglyceride (TG) presented to our ward. She had experienced sudden chest tightness, polypnea and fainting after going to the bathroom the morning of the second postoperative day and received emergency medical attention. Colour ultrasonography of the extremities showed no deep vein thrombosis. Lung computed tomography angiography (CTA) showed multiple embolisms scattered in both pulmonary artery branches. Thus, emergency interventional thrombolysis therapy was performed, followed by postoperative symptomatic treatment with drugs with thrombolytic, anticoagulant and protective activities. One week later, lung CTA showed a significant improvement in the PEs compared with those in the previous examination. Since the aetiology of PE and no obvious symptoms were discerned, the patient was discharged. Conclusion Although knee arthroscopy is a minimally invasive and quick procedure, the risk factors for PE in the perioperative period should be considered and fully evaluated to enhance PE detection. Moreover, a timely diagnosis and effective treatment are important measures to prevent and cure PE after knee arthroscopy. Finally, clear guidelines regarding VTE thromboprophylaxis following knee arthroscopy in patients with a low risk of VTE development are needed.