Effectiveness and safety of extended thromboprophylaxis in post-discharge patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The effect of extended thromboprophylaxis in improving the prognosis of adult patients with coronavirus disease 2019 (COVID-19) after discharge remains debatable. This meta-analysis was aimed to determine the advantages and disadvantages of extended thromboprophylaxis in these patients. METHODS: Different databases such as PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies that evaluated the effects of extended thromboprophylaxis in post-discharge patients with COVID-19 until 13 June 2022. The primary efficacy outcome was defined by the composite outcome of thromboembolism and all-cause mortality, and the safety outcome was defined by bleeding events. The odds ratios (ORs) and 95 % confidence intervals (CIs) of efficacy and safety outcomes were calculated using fixed- or random-effects model. Interaction analysis was performed to assess and compare observational studies and randomised controlled trials (RCTs). A sensitivity analysis was performed after excluding studies of poor quality. RESULTS: Eight studies involving 10,148 patients were included. The results confirmed that extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, was significantly associated with reduced composite outcome in high-risk post-discharge patients with COVID-19 (OR: 0.52; 95 % CI: 0.41-0.67, P = 0.000). Interaction analysis revealed that the effect estimates were consistent between the RCT and observational studies (Pinteraction = 0.310). Furthermore, extended thromboprophylaxis did not increase the risk of major bleeding events (OR: 1.64; 95 % CI: 0.95-2.82, P = 0.075). CONCLUSION: In post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, can significantly reduce the risk of thrombosis and all-cause mortality without increasing the risk of major bleeding events. REGISTRATION: PROSPERO CRD42022339399.

Extended post-discharge thromboprophylaxis in hospitalized COVID-19 patients.

INTRODUCTION: Hospitalized COVID-19 patients, particularly those with high-risk features, are at risk for venous and arterial thromboembolic events for approximately 30 days or more after hospital discharge. Extended post-hospital discharge thromboprophylaxis has potential to reduce this risk. AREAS COVERED: Recent cohort, registry, and randomized trial data on the topic of extended post-discharge thromboprophylaxis in COVID-19 inpatients are reviewed, and key patient subgroups at high thrombotic risk are highlighted, with antithrombotic guidelines on the topic discussed. EXPERT OPINION: COVID-19 inpatients with cardiovascular risk factors, advanced age, intensive care unit stay, or an IMPROVE VTE score of 4 or more or a score of 2 or 3 plus elevated D-dimers (> twice the upper limit of normal) or an IMPROVE-DD VTE score of ≥4 are at high thrombotic risk in the post-discharge period. These high-risk patient subgroups benefit from extended post-discharge thromboprophylaxis, specifically with rivaroxaban 10 mg daily for 35 days. Recent NIH and ISTH guidelines recommend or suggest this approach. Results from other clinical trials are pending.

Bemiparin Versus Enoxaparin for Extended Thromboprophylaxis in COVID-19 Patients at High Risk of Venous Thromboembolism

Introduction: Patients with COVID-19 are at increased risk of thromboembolic events during hospitalization and after discharge. Current guidelines recommend use of extended thromboprophylaxis in hospitalized COVID-19 patients who have high risk of post-discharge venous thromboembolism and low risk of bleeding. We aimed to report our experience regarding different low-molecular-weight heparins administered post-discharge in a COVID-19 patient population with high-thromboembolic and low-bleeding risk. Methods: This was a single-center, retrospective, observational study. Consecutive patients admitted with a confirmed diagnosis of COVID-19 between March 16 and July 16, 2020, were assessed for enrollment. Patients were included if they received prophylaxis with low-molecular-weight heparins after discharge, were ≥18 years of age, and completed follow-up. Pregnant women, children <18 years of age, patients with intensive care unit admission, and patients who experienced venous and/or arterial thromboembolism prior to discharge were excluded. Extended thromboprophylaxis with either enoxaparin 4000 IU once daily or bemiparin 3500 IU once daily was prescribed if a patient had a modified IMPROVE VTE score of ≥4, or a modified IMPROVE score of ≥2 and a D-dimer level of ≥2 times the reference range. Patients were followed-up for 30 days after discharge. Primary endpoint was occurrence of radiologically confirmed symptomatic venous thromboembolism (deep vein thrombosis and/or pulmonary embolism). Results: A total of 3498 consecutive patients were hospitalized with a diagnosis of COVID-19. Of them, 38 (20 women) received extended thromboprophylaxis. Mean of age was 66.6±15.7 years. Twenty-five patients received enoxaparin, and 13 received bemiparin. Three patients in the enoxaparin group and none of the patients in the bemiparin group experienced post-discharge venous thromboembolism (p=0.681). Major bleeding occurred in one patient in the enoxaparin group, and in zero patients in the bemiparin group (p=0.456). Conclusion: Enoxaparin and bemiparin have similar prophylactic properties when used for prevention of post-discharge venous thromboembolism in COVID-19 survivors who have high thromboembolic and low bleeding risk. © 2022 Ubiquity Press. All rights reserved.

Incidence, Risk Factors, and Timing of Macrovascular Thrombosis in the Post-COVID-19 Elderly and Assessing the Need and Duration of Extended Thromboprophylaxis: A Prospective Study

Background: COVID-19 infection causes a wide spectrum of macrovascular thrombosis, which has contributed significantly to morbidity and mortality in the elderly. Guidelines have recommended extended prophylaxis following discharge from the hospital for variable periods. The risk of thrombosis and the optimal duration of extended anticoagulation remain uncertain. Objectives: This study aimed at determining the overall incidence and timing of macrovascular thrombosis in post-COVID-19 elderly patients. It also aimed at finding out the predictive value of clinical severity, in-hospital anticoagulation, and discharge Ddimer values for the incidence of macrovascular thrombosis and overall mortality within 13 weeks following clinical recovery from acute COVID-19 infection in the elderly. Methods: In this study, 288 elderly patients with symptomatic acute COVID-19 infection discharged between August 1, 2020, and November 30, 2020, were enrolled. Details regarding the incidence of macrovascular thrombosis were collected through a telephone interview after 90 days. Data were tabulated and analyzed with IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY: IBM Corp.) Results: The number of macrovascular thrombotic events was significantly higher in group C (critical illness) than in the other two groups (17.9 vs. 1.8 and 1.1%, respectively) (P = 0.0005). Three (10.7%) patients died within 13 weeks of discharge in group C, versus one (0.6%) patient in groupM(mild to moderate illness) and none in group S (severe illness) (P = 0.0005). There were two macrovascular thrombotic events in the elevated D-dimer group versus one in the reduced D-dimer group (P = 0.135). The number of deaths was high in the elevated D-dimer group [2 (8.3%) vs. 0 (0), P = 0.053]. The cumulative incidence rate of macrovascular events in the post-COVID-19 elderly cohort 13 weeks after discharge was 3.12%. Conclusions: Elderly patients with a critical illness during hospitalization due to COVID-19 and elevated D-dimer values at discharge have the maximum risk of developing macrovascular thrombosis in the post-COVID-19 period. It is reasonable to recommend extended thromboprophylaxis for at least eight weeks in the post-COVID-19 elderly.