Emergence of institutional antithrombotic protocols for coronavirus 2019

Abstract

The coronavirus disease 2019 (COVID‐19), first identified in December 2019 in Wuhan, China, is a major public health crisis with new infections increasing exponentially worldwide.1.Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (27569) Google Scholar COVID‐19 is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) and has contributed to significant morbidity and mortality, including the development of coagulopathy.2.Guan W.J. Ni Z.Y. Hu Y. Liang W.H. Ou C.Q. He J.X. et al.China medical treatment expert group for Covid‐19. Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-20https://doi.org/10.1056/NEJMoa2002032Crossref PubMed Scopus (17356) Google Scholar Similar thrombotic and thromboembolic events have occurred during other viral outbreaks, including severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome, and influenza A H1N1.3.Chong P.Y. Chui P. Ling A.E. Franks T.J. Tai D.Y. Leo Y.S. et al.Analysis of deaths during the severe acute respiratory syndrome (SARS) epidemic in Singapore: challenges in determining a SARS diagnosis.Arch Pathol Lab Med. 2004; 128: 195-204Crossref PubMed Google Scholar, 4.Lew T.W.K. Kwek T.‐.K. Tai D. Earnest A. Loo S. Singh K. et al.Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome.JAMA. 2003; 290: 374-80Crossref PubMed Scopus (343) Google Scholar, 5.Arabi Y.M. Balkhy H.H. Hayden F.G. Bouchama A. Luke T. 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Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.Lancet. 2006; 367: 1075-9Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 9.Schmidt M. Horvath‐Puho E. Thomsen R.W. Smeeth L. Sorensen H.T. Acute infections and venous thromboembolism.J Intern Med. 2012; 271: 608-18Crossref PubMed Scopus (122) Google Scholar, 10.Rogers M.A. Levine D.A. Blumberg N. Flanders S.A. Chopra V. Langa K.M. Triggers of hospitalization for venous thromboembolism.Circulation. 2012; 125: 2092-9Crossref PubMed Scopus (132) Google Scholar Survival among patients with incident and recurrent VTE is significantly reduced, especially after PE.11.Heit J.A. Silverstein M.D. Mohr D.N. Petterson T.M. O'Fallon W.M. Melton 3rd, L.J. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population‐based, cohort study.Arch Intern Med. 1999; 159: 445-53Crossref PubMed Scopus (618) Google Scholar Hospitalized patients with acute medical illness, including infections such as pneumonia, are at increased risk of VTE, both in‐hospital and for an extended period of time (up to 45 days) after hospital discharge.8.Smeeth L. Cook C. Thomas S. Hall A.J. Hubbard R. Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.Lancet. 2006; 367: 1075-9Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 9.Schmidt M. Horvath‐Puho E. Thomsen R.W. Smeeth L. Sorensen H.T. Acute infections and venous thromboembolism.J Intern Med. 2012; 271: 608-18Crossref PubMed Scopus (122) Google Scholar, 12.Spyropoulos A.C. Anderson Jr, F.A. FitzGerald G. Decousus H. Pini M. 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Harjola V.‐.P. et al.2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1419) Google Scholar, 16.Wang L. Sengupta N. Baser O. Risk of venous thromboembolism and benefits of prophylaxis use in hospitalized medically ill US patients up to 180 days post‐hospital discharge.Thromb J. 2011; 9: 1-10Crossref PubMed Scopus (16) Google Scholar Despite this well‐established association,8.Smeeth L. Cook C. Thomas S. Hall A.J. Hubbard R. Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.Lancet. 2006; 367: 1075-9Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 9.Schmidt M. Horvath‐Puho E. Thomsen R.W. Smeeth L. Sorensen H.T. Acute infections and venous thromboembolism.J Intern Med. 2012; 271: 608-18Crossref PubMed Scopus (122) Google Scholar, 10.Rogers M.A. Levine D.A. Blumberg N. Flanders S.A. Chopra V. Langa K.M. Triggers of hospitalization for venous thromboembolism.Circulation. 2012; 125: 2092-9Crossref PubMed Scopus (132) Google Scholar there are few data specifically addressing VTE in patients recently hospitalized with COVID‐19 infections.17.Danzi G.B. Loffi M. Galeazzi G. Gherbesi E. Acute pulmonary embolism and COVID‐19 pneumonia: a random association?.Eur Heart J. 2020; 41: 1858https://doi.org/10.1093/eurheartj/ehaa254Crossref PubMed Scopus (418) Google Scholar, 18.Xie Y. Wang X. Yang P. Zhang S. COVID‐19 complicated by acute pulmonary embolism.Radiol Cardiothorac Imag. 2020; 2Google Scholar Indeed, infection‐associated VTE might account for a substantial burden of incident or recurrent VTE among those with COVID‐19. In addition, small‐vessel hyaline thrombus formation has been described in autopsies of patients with COVID pneumonia.19.Yao X.H. Li T.Y. He Z.C. Ping Y.F. Liu H.W. Yu S.C. et al.A pathological report of three COVID‐19 cases by minimally invasive autopsies.Zhonghua Bing Li Xue Za Zhi. 2020; 49: E009PubMed Google Scholar There is increasing concern that mortality seen across all age groups may be secondary to PE, as 31% incidence of thrombotic complications in ICU patients with COVID‐19 infections is recently reported. PE was the most frequent thrombotic complication and contributed to 81% of thrombotic complications.20.Klok F.A. Kruip M.J.H.A. van der Meer N.J.M. Arbous M.S. Gommers D.J. Kant K.M. et al.Incidence of thrombotic complications in critically ill ICU patients with COVID‐19.Thromb Res. 2020; https://doi.org/10.1016/j.thromres.2020.04.013Google Scholar To improve outcomes, targeted prophylaxis efforts to improve coagulopathy and reduce incident VTE in patients with acute infectious diseases, specifically COVID‐19, may be advantageous. Currently, VTE prophylaxis duration is mainly limited to the period of hospitalization,21.Kahn S.R. Lim W. Dunn A.S. Cushman M. Dentali F. Akl E.A. et al.Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence‐based clinical practice guidelines.Chest. 2012; 141: e195S-226SAbstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar but most VTE events occur within the first month following hospital discharge.22.Huang W. Goldberg R.J. Anderson F.A. Kiefe C.I. Spencer F.A. Secular trends in occurrence of acute venous thromboembolism: the Worcester VTE study (1985–2009).Am J Med. 2014; 127: 829-39Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar Recent data support the finding that an elevated D‐dimer (>2× upper limit of normal [ULN]) is an important novel biomarker in identifying a high‐VTE‐risk population that would benefit from extended thromboprophylaxis, an observation that is especially important in the hospitalized COVD‐19 population.23.Spyropoulos A.C. Lipardi C. Xu J. Peluso C. Spiro T.E. De Sanctis Y. et al.Modified IMPROVE VTE risk score and elevated D‐dimer identify a high venous thromboembolism risk in acutely ill medical population for extended thromboprophylaxis.TH Open. 2020; 4: e59-65Crossref PubMed Google Scholar If all hospitalized patients received universally effective prophylaxis, one quarter of the VTE burden in the community would be prevented.24.Heit J.A. Crusan D.J. Ashrani A.A. Petterson T.M. Bailey K.R. Effect of near‐universal hospitalization‐based prophylaxis on annual number of venous thromboembolism events in the US.Blood. 2017; 130: 109-14Crossref PubMed Scopus (73) Google Scholar To further reduce the VTE burden, better prophylaxis strategies are needed, which include prolonging VTE prophylaxis beyond hospital dismissal. There are several concerns linked to the VTE prevention in COVID‐19 patients: How can we limit the risk of VTE among patients who are hospitalized? Do we use similar prophylaxis in the common medical ward and in the intensive care unit (ICU)? How do we manage patients with COVID‐19 who are already taking oral anticoagulants or antiplatelets? To address these concerns, several leading national and international health care institutions have developed protocols to help guide health care professionals on how to manage thrombotic and antithrombotic therapy related to COVID‐19 during this pandemic. Currently, there is significant variability in expertise, as many of the existing protocols derived are from sporadic reports and small retrospective studies. Given the lack of large prospective cohorts, the current document represents an effort to provide several simple and easy‐to‐follow algorithms to be considered as an interim clinical guidance since the knowledge and therapeutics in managing COVID‐19 is rapidly evolving. The aim of this document is to provide clinicians and hospital systems a template on safe and effective use of antithrombotic medications in health care systems affected by the COVID‐19 pandemic from an institutional perspective, including post–hospital discharge prophylaxis. Patients with COVID‐19 and underlying cardiovascular disease and comorbidities have greater morbidity and mortality from COVID‐19.25.Driggin E. Madhavan M.V. Bikdeli B. Chuich T. Laracy J. Bondi‐Zoccai G. et al.Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID‐19) pandemic.J Am Coll Cardiol. 2020; 75: 2352-71https://doi.org/10.1016/j.jacc.2020.03.031Crossref PubMed Scopus (1239) Google Scholar, 26.Madjid M. Safavi‐Naeini P. Solomon S.D. Vardeny O. Potential effects of coronaviruses on the cardiovascular system. A review.JAMA Cardiol. 2020; https://doi.org/10.1001/jamacardio.2020.1286Crossref PubMed Scopus (1101) Google Scholar Common laboratory abnormalities include lymphopenia and increase in lactate dehydrogenase and inflammatory markers such as C‐reactive protein, D‐dimer, ferritin, interleukin (IL)‐6, and fibrinogen.27.Tang N. Li D. Wang X. Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.J Thromb Haemost. 2020; 18: 844-7Abstract Full Text Full Text PDF PubMed Scopus (3436) Google Scholar, 28.Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. et al.Clinical course and risk factors for mortality of adult inpatients with COVID‐19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-62Abstract Full Text Full Text PDF PubMed Scopus (15912) Google Scholar Thrombocytopenia29.Lippi G. Plebani M. Michael H.B. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID‐19) infections: a meta‐analysis.Clin Chim Acta. 2020; 506: 145-8Crossref PubMed Scopus (964) Google Scholar and increased D‐dimer levels30.Lippi G. Favaloro E.J. D‐dimer is associated with severity of coronavirus disease 2019 (COVID‐19): a pooled analysis.Thromb Haemost. 2020; 120: 876-8Crossref PubMed Scopus (361) Google Scholar are the most consistent laboratory abnormalities associated with a higher risk of developing severe COVID‐19. Therefore, several protocols suggest measuring D‐dimers, prothrombin time, and platelet counts to help assess COVID‐19 severity. Whether the very elevated D‐dimers seen in very sick COVID‐19 patients represent severe coagulopathy or are markers of a severe inflammatory “cytokine storm” is not known. Hospitalized patients with acute medical illness, including COVID‐19, should have an assessment of VTE versus bleeding risk. There are several risk stratification tools available (eg, the Caprini, IMPROVE [International Medical Prevention Registry on Venous Thromboembolism], and Padua models) to assist the health care provider in assessing VTE risk among hospitalized patients.31.Barbar S. Noventa F. Rossetto V. Ferrari A. Brandolin B. Perlati M. et al.A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score.J Thromb Haemost. 2010; 8: 2450-7Abstract Full Text Full Text PDF PubMed Scopus (701) Google Scholar, 32.Arcelus J.I. Candocia S. Traverso C.I. Fabrega F. Caprini J.A. Hasty J.H. Venous thromboembolism prophylaxis and risk assessment in medical patients.Semin Thromb Hemost. 1991; 17: 313-8PubMed Google Scholar, 33.Liu X. Liu C. Chen X. Wu W. Lu G. 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Angiotensin‐converting enzyme 2 (ACE2) as a SARS‐CoV‐2 receptor: molecular mechanisms and potential therapeutic target.Intensive Care Med. 2020; 46: 586-90Crossref PubMed Scopus (1567) Google Scholar There is a suggestion from in vitro evidence that LMWH may competitively bind to coronavirus. Heparins as a class may suppress the cytokine storm induced by activated T cells, macrophages, and monocytes/neutrophils, all with increased IL expression (including IL‐2R/6).41.Mousavi S. Moradi M. Khorshidahmad T. Motamedi M. Anti‐inflammatory effects of heparin and its derivatives: a systematic review.Adv Pharmacol Sci. 2015; 2015: 507151Crossref PubMed Scopus (189) Google Scholar Empiric evidence supports use of treatment dose unfractionated heparin (UFH) as improving thrombosis‐free survival in acute respiratory distress syndrome with influenza A H1N1 but not coronavirus.42.Obi A.T. Tignanelli C.J. Jacobs B.N. Arya S. Park P.K. 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Interim guidance 28 January 2020. [Accessed 2020 March 13] Available from https://www.who.int/docs/default‐source/coronaviruse/clinical‐management‐of‐novel‐cov.pdf.Google Scholar Obese patients with body mass index (BMI) >30 kg/m2 have increased risk of VTE,46.Stein P.D. Beemath A. Olson R.E. Obesity as a risk factor in venous thromboembolism.Am J Med. 2005; 118: 978-80Abstract Full Text Full Text PDF PubMed Scopus (428) Google Scholar recurrent VTE,47.Eichinger S. Hron G. Bialonczyk C. Hirschl M. Minar E. Wagner O. et al.Overweight, obesity, and the risk of recurrent venous thromboembolism.Arch Intern Med. 2008; 168: 1678-83Crossref PubMed Scopus (234) Google Scholar and postthrombotic syndrome48.Galanaud J.P. Holcroft C.A. Rodger M.A. Kovacs M.J. Betancourt M.T. Wells P.S. et al.Predictors of post‐thrombotic syndrome in a population with a first deep vein thrombosis and no primary venous insufficiency.J Thromb Haemost. 2013; 11: 474-80Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar; however, prior studies have mainly focused VTE prophylaxis on extreme obesity defined by BMI >40 kg/m2. As the distribution of LMWH is weight based, the efficacy of standard doses may be decreased due to the effects of plasma drug distribution and pharmacokinetics in obese individuals.49.Freeman A.L. Pendleton R.C. Rondina M.T. Prevention of venous thromboembolism in obesity.Expert Rev Cardiovasc Ther. 2010; 8: 1711-21Crossref PubMed Scopus (82) Google Scholar Furthermore, in a subgroup analysis of obese patients from the PREVENT (Prevention of Recurrent Thromboembolism) trial, dalteparin lost its thromboprophylactic benefit in patients with BMI >35 kg/m2.50.Kucher N. Leizorovicz A. Vaitkus P.T. Cohen A.T. Turpie A.G.G. Olsson C.‐.G. et al.Efficacy and safety of fixed low‐dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial.Arch Intern Med. 2005; 165: 341-5Crossref PubMed Scopus (103) Google Scholar The ITOHENOX (Adjusted Value of Thromboprophylaxis in Hospitalized Obese Patients: A Comparative Study of Two Regimens of Enoxaparin) study shows in medically obese inpatients that thromboprophylaxis with enoxaparin 60 mg provides higher control of anti‐Xa activity, without more bleeding complications than the standard enoxaparin regimen.51.Miranda S. Le Cam‐Duchez V. Benichou J. Donnadieu N. Barbay V. Le Besnerais M. et al.Adjusted value of thromboprophylaxis in hospitalized obese patients: a comparative study of two regimens of enoxaparin: The ITOHENOX study.Thromb Res. 2017; 155: 1-5Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Based on these observations and guidance, several of the protocol strategies suggest the use of thromboprophylaxis with LMWH at prophylactic or intermediate doses (ie, 40 mg s.c. daily or 40 mg s.c. twice daily, especially for BMI > 30 kg/m2) as the preferred agent over UFH, unless patients have severe renal insufficiency (creatinine clearance [CrCl] < 30 mL/min or even 15 mL/min) (Table 1). This strategy avoids the increased health care worker exposure, use of limited resources such as personal protective equipment for frequent blood draws, and the time needed to achieve therapeutic activated partial thromboplastin times. There are randomized trials that are being initiated studying intermediate to high doses of LMWH in the management of patients with COVID‐19 with severe illness.Table 1Comparisons of different institutional protocols proposed in United States and France in case of COVID‐19Froedtert Health & The Medical College of Wisconsin, USANorthwell Health, USANorthshore University Health System, USAUniversity hospital of Amiens, FRAUniversity hospital of Montpellier, FRAUniversity Hospital of Rennes, FRAUniversity Hospital of Saint‐Etienne, FRAWhich patients?In‐ and outpatientsInpatientsIn‐ and outpatientsOutpatientsIn‐ and outpatientsInpatients and elderly in establishmentICU patientsThrombotic risk assessmentYesYesYesYesYesNot mentionedNot mentionedCriteria for VTE riskUse of Wells’ CriteriaIMPROVE VTE scoreD‐dimerUse of ISTH DIC scoreIMPROVE VTE scoreD‐dimerUse of ISTH DIC scoreImmobilization > 48 h, cancer, recent surgery, personal history of VTE, BMI > 30 kg/m2, age > 70 y oldThrombotic risk and ISTH DIC scoreNANAHemostasis surveillanceNot mentionedNot mentionedYesNot mentionedYesYesYesAssessment of bleeding riskYesYesNot mentionedNot mentionedYesYesNot mentionedProposed prophylactic treatmentsPatients hospitalized with suspected or confirmed COVID‐19, VTE prophylaxis with enoxaparin at prophylactic or intermediate doses (ie, 40 mg s.c. daily or 40 mg s.c. twice daily, especially for BMI > 40 kg/m2) as the preferred agent over UFH, unless patients have acute renal failure or chronic kidney disease (CrCl < 15 mL/min); if CrCl < 15 mL/min, then UFH 5000 IU s.c. 3 times daily for BMI < 40 kg/m2 or 7500 IU s.c. twice daily for BMI > 40 kg/m2Suggestion of the use of thromboprophylaxis with enoxaparin at prophylactic or intermediate doses (ie, 40 mg s.c. daily or 40 mg s.c. twice daily, especially for BMI > 30 kg/m2) as the preferred agent over UFH, unless patients have severe renal insufficiency (CrCl < 15 mL/min); if CrCl < 15 mL/min, then UFH 5000 IU s.c. 3 times daily for BMI < 30 kg/m2 or 7500 IU s.c. 3 times daily for BMI > 30 kg/m2For moderate to severe with DIC and no overt bleed, consider intermediate dose of LMWHPatients with COVID‐19 with at least 1 VTE risk factor will receive thrombosis prophylaxis with LMWH for at least 10 d (auto‐injection should be preferred)For all inpatients: enoxaparin 4000 IU/d for at least 14 dFor all hospitalized patients except with bleeding syndrome and BMI < 30 kg/m2: enoxaparin 4000 IU/dIf BMI > 30 kg/m2 or severe inflammatory syndrome or femoral venous catheter: Enoxaparin 6000 IU/dMultimodal thromboprophylaxis with pharmacologic + mechanical compression should be used in ICU settingsVTE prophylaxis with daily LMWH, or twice daily subcutaneous UFH is strongly recommended (LMWH may be advantageous to reduce PPE use and provider exposure)For outpatients with elevated D‐dimers (>2 N) or with VTE risk factors (personal history of VTE, known thrombophilia, lower limb paralysis, active cancer, immobilization > 7 d, age > 60 y old): enoxaparin 4000 IU/d for at least 14 dFor all hospitalized patients except with bleeding syndrome and BMI 30‐40 kg/m2: enoxaparin 6000 IU/dIf BMI > 40 kg/m2: enoxaparin 4000 IU × 2/dExtended VTE prophylaxis with rivaroxaban 10 mg p.o. daily for 30 d should be considered at hospital discharge, without bleeding risk factors; if D‐dimer is > 2× ULN during the hospitalization and Previous VTE or ≥2 of the following characteristics are met: Age > 60, ICU stay, current lower limb paralysis or paresis, current cancer, known thrombophiliaPatients hospitalized with COVID‐19, especially those with an IMPROVE VTE score of ≥4 or over 60 y and with elevated D‐dimers and without bleeding risk factors, should be strongly considered for extended thromboprophylaxis up to 39 d after hospital discharge with either enoxaparin 40 mg s.c. daily or rivaroxaban 10 mg p.o. dailyContinue postdischarge prophylaxis to all patients with COVID‐19 over 50 y old; consider extending prophylaxis to 6 wk rivaroxaban or betrixaban in patients with any additional risk factor: prior history of thrombosis, ICU stay, cancer, thrombophilia, paralysisIf GFR < 30 mL/min (Cockroft): UFH 5000 IU × 2/dFor all hospitalized patients except with bleeding syndrome and BMI > 40 kg/m2: enoxaparin BMI × 2/d (eg BMI = 42 kg/m2), then enoxaparin 4000 IU × 2/dIf CrCl < 30 mL/min: calciparin 0.2 mL × 3/dPatients with a CrCl <30 mL/min were excluded from the clinical trials of extended prophylaxis; therefore, the risk and benefit in this patient population is not known and extended prophylaxis is not recommendedFor outpatients diagnosed with mild or moderate COVID‐19 and low risk of bleeding, consider VTE prophylaxis as aboveIf BMI ≥ 40 kg/m2: Enoxaparin 4000 IU × 2/dFor all hospitalized patients except with bleeding syndrome and GFR < 15 mL/min: tinzaparin 3500 IU/d (we do not suggest use of calciparin 0.2 mL × 3/d to avoid accumulationIf high bleeding risk: discuss preventive anticoagulation; if hospitalized patients: compression bands (BIFLEX) if no peripheral artery disease; in ICU patients: intermittent pneumatic compressionIn ICU patients: proceed as for hospitalized patientsIn elderly patients in establishment: enoxaparin 4000 IU/dPatients with long‐term anticoagulationAssuming no contraindications, DOACs are considered first line for anticoagulation for most patients and preferred to coumadin. Alternatively, dose‐adjusted warfarin with extended INR monitoring should be an optionIf possible, patients may be switched to dabigatran as the DOAC of choice; alternatively, dose‐adjusted warfarin with extended INR monitoring should be an optionAssuming no contraindications, DOACs preferred to coumadin for chronically anticoagulated COVID‐19 outpatientsNot mentionedIn hospitalized patients: replace by LWMH (in the absence of contraindication)Not mentionedNot mentionedLower limb ultrasound examAs usual; not systematicNot mentionedNot mentionedNot mentionedAs usual; not systematicAs usual; not systematicFast (4 points):•Systematic at days 7, 14, and 21•Earlier if patient gets worse without any evident cause•Earlier if femoral venous catheter•Before first chair settingBMI, body mass index; COVID‐19, coronavirus disease 2019; CrCl, creatinine clearance; DIC, disseminated intravascular coagulation; DOAC, direct oral anticoagulant; GFR, glomerular filtration rate; ICU, intensive care unit; INR, International Normalized Ratio; LMWH, low‐molecular‐weight heparin; NA, not available; PPE, personal protective equipment; s.c., subcutaneous; UFH, unfractioned heparin; IU, international units; ULN, upper limit normal; VKA, vitamin K antagonist; VTE, venous thromboembolism. Open table in a new tab BMI, body mass index; COVID‐19, coronavirus disease 2019; CrCl, creatinine clearance; DIC, disseminated intravascular coagulation; DOAC, direct oral anticoagulant; GFR, glomerular filtration rate; ICU, intensive care unit; INR, International Normalized Ratio; LMWH, low‐molecular‐weight heparin; NA, not available; PPE, personal protective equipment; s.c., subcutaneous; UFH, unfractioned heparin; IU, international units; ULN, upper limit normal; VKA, vitamin K antagonist; VTE, venous thromboembolism. It is important to recognize the