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Thromboprophylaxis in COVID-19 - Rationale and considerations.

ABSTRACT: The Corona Virus Disease-2019 (COVID-19) pandemic is associated with a very high incidence of thrombotic complications. The exact mechanisms for this excess risk for clots have not been elucidated although one of the often-quoted pathophysiological entity is immunothrombosis. Recognition of thrombotic complications early on in this pandemic led to an over-explosion of studies which looked at the benefits of anticoagulation to mitigate this risk. In this review, we examine the rationale for thromboprophylaxis in COVID-19 with particular reference to dosing and discuss what may guide the decision-making process to consider anticoagulation. In addition, we explore the rationale for thrombosis prevention measures in special populations including outpatient setting, pregnant females, children, those with high body mass index and those on extracorporeal membrane oxygenation.

SUBMITTER: Bristogiannis S

PROVIDER: S-EPMC8299150 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Thromboprophylaxis in COVID-19 - Rationale and considerations.

Bristogiannis Sotirios S Swan Dawn D Thachil Jecko J

Advances in biological regulation 20210723

The Corona Virus Disease-2019 (COVID-19) pandemic is associated with a very high incidence of thrombotic complications. The exact mechanisms for this excess risk for clots have not been elucidated although one of the often-quoted pathophysiological entity is immunothrombosis. Recognition of thrombotic complications early on in this pandemic led to an over-explosion of studies which looked at the benefits of anticoagulation to mitigate this risk. In this review, we examine the rationale for throm ...[more]

PMID: 34332403

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Project description:BackgroundPatients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.ObjectiveTo determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.DesignProspective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).SettingDone during 2021 to 2022 among 127 U.S. hospitals.ParticipantsAdults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation.Intervention2.5 mg of apixaban versus placebo twice daily for 30 days.MeasurementsThe primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding.ResultsEnrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment.LimitationsThe introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity.ConclusionThe incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive.Primary funding sourceNational Institutes of Health.

Project description:In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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Thromboprophylaxis in COVID-19 - Rationale and considerations.

Publications

Thromboprophylaxis in COVID-19 - Rationale and considerations.

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