Use of low-molecular-weight heparin in COVID-19 patients

Abstract

Marone and Rinaldi1Marone E.M. Rinaldi L.F. Upsurge of deep venous thrombosis in patients affected by COVID-19: preliminary data and possible explanations.J Vasc Surg Venous Lymphat Disord. 2020; 8: 694-695Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar in their study reported cases of deep venous thrombosis (DVT) in hospitalized patients with 2019 novel coronavirus disease (COVID-19). We appreciate the efforts by the authors to present preliminary data on COVID-19-related DVT in their practicing institution and to discuss the possible underlying mechanisms of DVT. According to the authors, administration of anticoagulant/therapeutic doses of low-molecular-weight heparin (LMWH) in hospitalized COVID-19 patients, instead of prophylactic doses, is the current practice in their practicing institution. Although some may have concern of increased risk of bleeding, bleeding does not appear to be a major manifestation of COVID-19. A higher than traditional standard prophylactic dose of LMWH as adopted in the authors' institution should be encouraged because there is possibly more risk of venous thromboembolism in hospitalized COVID-19 patients than in their non-COVID-19 counterparts. Particularly, Middeldorp et al2Middeldorp S. Coppens M. van Haaps T.F. Foppen M. Vlaar A.P. Müller M.C. et al.Incidence of venous thromboembolism in hospitalized patients with COVID-19.J Thromb Haemost. 2020 May 5; ([Epub ahead of print])Crossref PubMed Scopus (902) Google Scholar reported that about 20% of the included COVID-19 patients had venous thromboembolism despite routine thromboprophylaxis with prophylactic doses of LMWH. A comparison with the largest randomized controlled trial thus far of LMWH for the prevention of venous thromboembolism in acutely ill medical patients (non-COVID-19) that reported a thromboprophylaxis failure rate of only 2.77% indicated that the standard prophylactic dose of LMWH in COVID-19 patients may be inadequate. A higher than usual rate of thromboprophylaxis failure may be due to an increasingly recognized hypercoagulable state with COVID-19 in which a number of changes in circulating prothrombotic factors have been reported in COVID-19 patients: elevated factor VIII level, elevated fibrinogen level, circulating prothrombotic microparticles, and presence of neutrophil extracellular traps.3Ranucci M. Ballotta A. Di Dedda U. Bayshnikova E. Dei Poli M. Resta M. et al.The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome.J Thromb Haemost. 2020; 18: 1747-1751Crossref PubMed Scopus (574) Google Scholar,4Panigada M. Bottino N. Tagliabue P. Grasselli G. Novembrino C. Chantarangkul V. et al.Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.J Thromb Haemost. 2020; 18: 1738-1742Crossref PubMed Scopus (801) Google Scholar These prothrombotic changes are not usually detected in acutely ill medical patients without COVID-19, in whom the efficacy of standard prophylactic dosing of LMWH is established. In addition, it has become increasingly clear that obesity is one of the biggest risk factors for severe COVID-19 disease, and therefore obese patients may constitute a significant proportion of hospitalized COVID-19 patients.5Caussy C. Wallet F. Laville M. Disse E. Obesity is associated with severe forms of COVID-19.Obesity (Silver Spring). 2020; 28: 1175Crossref PubMed Scopus (109) Google Scholar Because high body weight correlates with low anti-factor Xa levels, an anti-factor Xa-guided individualized dosing approach with LMWH may also be adopted in the obese hospitalized COVID-19 population to further reduce the risk of thromboprophylaxis failure. We look forward to studies reporting outcomes on anti-factor Xa-guided approach for dosing of LMWH among COVID-19 patients. ReplyJournal of Vascular Surgery: Venous and Lymphatic DisordersVol. 8Issue 5PreviewThe remarks made by Kow and Hasan1 regarding the use of low-molecular-weight heparin (LMWH) in hospitalized COVID-19 patients are greatly appreciated since they focus on one of the most important aspects concerning the treatment of this disease, namely, thromboprophylaxis. In fact, since our latest letter was published in this Journal, suggesting a close correlation between COVID-19 and deep venous thrombosis (DVT),2 a number of studies have followed, confirming this view and providing evidence of the fact that respiratory infection is also responsible for a systemic procoagulant activity,3-5 which can lead to different clinical manifestations ranging from DVT to septic intravascular coagulation, not only in the most critical cases (patients in intensive care unit) but in all in-hospital patients. Full-Text PDF