Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Anticoagulantes orais diretos para o tratamento da trombose venosa profunda: revisão de revisões sistemáticas / Direct oral anticoagulants for treatment of deep vein thrombosis: overview of systematic reviews

A number of limitations of standard therapy with warfarin for deep vein thrombosis (DVT) have been established. This overview of systematic reviews presents the baseline results for efficacy and safety of the new direct oral anticoagulants (DOACs) thrombin inhibitors, and activated factor X (Xa) inhibitors in patients with DVT. Searches were run on PubMed and the Cochrane Database of Systematic Reviews. Twenty-three studies were retrieved, and one systematic review was judged eligible. This review scored maximum according to AMSTAR criteria and included 7,596 patients for analysis of thrombin inhibitors and 16,356 patients for analysis of factor Xa inhibitors. The results of the meta-analysis indicate that DOACs are similar for DVT treatment when compared to standard treatment with warfarin. The incidence of major bleeding is somewhat lower in patients treated with factor Xa inhibitors and similar to standard therapy when treated with direct thrombin inhibitors

A terapia padrão com varfarina para a trombose venosa profunda (TVP) tem uma série de limitações já estabelecidas. Essa revisão de revisões sistemáticas elenca os principais resultados de eficácia e segurança dos anticoagulantes orais diretos (DOACs), inibidores da trombina e do fator X ativado (Xa), em pacientes com TVP. A pesquisa foi realizada nas bases PubMed e Cochrane Database of Systematic Reviews. Foram recuperados 23 estudos, e uma revisão sistemática foi considerada elegível. Essa revisão atingiu escore máximo no AMSTAR e incluiu 7.596 pacientes para análise dos inibidores da trombina e 16.356 pacientes para a análise dos inibidores do fator Xa. Os resultados da metanálise indicam que os DOACs apresentam eficácia similar à terapia padrão no tratamento da TVP. A incidência de sangramento maior é um pouco menor nos pacientes tratados com os inibidores do fator Xa e similar à terapia padrão no tratamento com inibidores diretos da trombina

Tratamento de linfocele inguinal pós-operatória com injeção de cola de fibrina: relato de caso / Treatment of postoperative inguinal lymphocele with fibrin glue injection: case report

O paciente desenvolveu linforragia na região inguinal direita, depois de ponte aorto-bifemoral com enxerto de dácron®. Não respondeu ao tratamento conservador com cuidados locais e compressão. Foi realizado exame de ultra-sonografia Doppler, que evidenciou grande linfocele (6,4 x 3,36 x 6,1 cm), tratada pelo esvaziamento da loja por aspiração e injeção de cola de fibrina (1,6 mL) em seu interior. O paciente se recuperou sem intercorrências e sem recidiva, após 3 meses de seguimento.

The patient developed lymphatic drainage in the right groin after an aortobifemoral bypass with Dacron® graft. Conservative treatment with local wound care and compression was unsuccessful. Duplex scan showed a 6.4 x 3.36 x 6.1 cm lymphocele, which was treated by aspiration and injection of fibrin glue (1.6 mL). The patient recovered uneventfully and without recurrence after a 3-month follow-up.