Download PDF
Semin Thromb Hemost 2023; 49(01): 062-072
DOI: 10.1055/s-0042-1744302
Review Article

To Anticoagulate or Not to Anticoagulate in COVID-19: Lessons after 2 Years

John G. Rizk‡   *
1   Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, Maryland
,
Aashish Gupta‡   *
2   John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, Louisiana
,
Jose G. Lazo Jr.   *
3   UCSF Medical Center, University of California, San Francisco, San Francisco, California
,
Partha Sardar
2   John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, Louisiana
,
Brandon Michael Henry
4   Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
5   Disease Prevention and Intervention & Population Health Programs, Texas Biomedical Research Institute, San Antonio, Texas
,
Carl J. Lavie
2   John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, Louisiana
,
Mark B. Effron
2   John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, Louisiana
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

A hypercoagulable state associated with coronavirus disease 2019 (COVID-19) has been well documented and is believed to be strongly supported by a proinflammatory state. The hypercoagulable state in turn results in increased incidence of arterial and venous thromboembolism (VTE) seen in hospitalized COVID-19 when compared with hospitalized non-COVID-19 patient cohorts. Moreover, patients with arterial or VTE and COVID-19 have higher mortality compared with COVID-19 patients without arterial or VTE. Prevention of arterial or VTE thus remains an essential question in the management of COVID-19 patients, especially because of high rates of reported microvascular and macrovascular thrombosis. This has prompted multiple randomized control trials (RCTs) evaluating different anticoagulation strategies in COVID-19 patients at various stages of the disease. Herein, we review findings from RCTs in the past 2 years of antithrombotic therapy in critically ill hospitalized patients, noncritically ill hospitalized patients, patients postdischarge from the hospital, and outpatients. RCTs in critically ill patients demonstrated therapeutic dose anticoagulation does not improve outcomes and has more bleeding than prophylaxis dose anticoagulant in these patients. Trials in noncritically ill hospitalized patients showed a therapeutic dose anticoagulation with a heparin formulation might improve clinical outcomes. Anticoagulation with a direct oral anticoagulant posthospital discharge may improve outcomes, although there is a large RCT in progress. Nonhospitalized COVID-19 patients have an insufficient burden of events to be candidates for antithrombotic therapy. Anticoagulation in pregnant and lactating patients with COVID-19, as well as antiplatelet therapy for COVID-19, is also reviewed.

Keywords

COVID-19 - anticoagulation - thrombosis - bleeding

* These authors contributed equally (co-first authors).




Publication History

Article published online:
25 April 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-immunomodulatory therapy in COVID-19. Drugs 2020; 80 (13) 1267-1292
    CrossrefPubMedGoogle Scholar
  • 2 Rizk JG, Forthal DN, Kalantar-Zadeh K. et al. Expanded Access Programs, compassionate drug use, and Emergency Use Authorizations during the COVID-19 pandemic. Drug Discov Today 2021; 26 (02) 593-603
    CrossrefPubMedGoogle Scholar
  • 3 Rizk JG, Wenziger C, Tran D. et al. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use associated with reduced mortality and other disease outcomes in US Veterans with COVID-19. Drugs 2022; 82 (01) 43-54
    CrossrefPubMedGoogle Scholar
  • 4 Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Authors' reply to Vrachatis et al. “Pharmaco-Immunomodulatory Therapy I COVID-19”. Drugs 2020; 80 (14) 1501-1503
    CrossrefPubMedGoogle Scholar
  • 5 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323 (11) 1061-1069
    CrossrefPubMedGoogle Scholar
  • 6 Zhou F, Yu T, Du R. 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 (10229): 1054-1062
    CrossrefPubMedGoogle Scholar
  • 7 Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020; 58 (07) 1021-1028
    CrossrefPubMedGoogle Scholar
  • 8 Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemost 2020; 120 (05) 876-878
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Carpenè G, Onorato D, Nocini R. et al. Blood lactate concentration in COVID-19: a systematic literature review. Clin Chem Lab Med 2021; 60 (03) 332-337
    CrossrefPubMedGoogle Scholar
  • 10 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020; 506: 145-148
    CrossrefPubMedGoogle Scholar
  • 11 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
    CrossrefPubMedGoogle Scholar
  • 12 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 (04) 844-847
    CrossrefPubMedGoogle Scholar
  • 13 Henry BM, Benoit SW, de Oliveira MHS, Lippi G, Favaloro EJ, Benoit JL. ADAMTS13 activity to von Willebrand factor antigen ratio predicts acute kidney injury in patients with COVID-19: evidence of SARS-CoV-2 induced secondary thrombotic microangiopathy. Int J Lab Hematol 2021; 43 (Suppl. 01) 129-136
    CrossrefPubMedGoogle Scholar
  • 14 Favaloro EJ, Henry BM, Lippi G. Increased VWF and decreased ADAMTS-13 in COVID-19: creating a milieu for (micro)thrombosis. Semin Thromb Hemost 2021; 47 (04) 400-418
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Henry BM, Cheruiyot I, Benoit JL. et al. Circulating levels of tissue plasminogen activator and plasminogen activator inhibitor-1 are independent predictors of coronavirus disease 2019 severity: a prospective, observational study. Semin Thromb Hemost 2021; 47 (04) 451-455
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Poissy J, Goutay J, Caplan M. et al; Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation 2020; 142 (02) 184-186
    CrossrefPubMedGoogle Scholar
  • 17 Suh YJ, Hong H, Ohana M. et al. Pulmonary embolism and deep vein thrombosis in COVID-19: a systematic review and meta-analysis. Radiology 2021; 298 (02) E70-E80
    CrossrefPubMedGoogle Scholar
  • 18 Nielsen HK. Pathophysiology of venous thromboembolism. Semin Thromb Hemost 1991; 17 (Suppl. 03) 250-253
    PubMedGoogle Scholar
  • 19 Green D. Coagulation cascade. Hemodial Int 2006; ;10 Suppl 2: S2-S4
    CrossrefPubMedGoogle Scholar
  • 20 Zhong H, Waresi M, Zhang W. et al. NOD2-mediated P2Y12 upregulation increases platelet activation and thrombosis in sepsis. Biochem Pharmacol 2021; 194: 114822
    CrossrefPubMedGoogle Scholar
  • 21 Walsh PN. Platelet coagulation-protein interactions. Semin Thromb Hemost 2004; 30 (04) 461-471
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Savchenko AS, Martinod K, Seidman MA. et al. Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development. J Thromb Haemost 2014; 12 (06) 860-870
    CrossrefPubMedGoogle Scholar
  • 23 Zuo Y, Yalavarthi S, Shi H. et al. Neutrophil extracellular traps in COVID-19. JCI Insight 2020; 5 (11) 138999
    PubMedGoogle Scholar
  • 24 Gupta A, Madhavan MV, Sehgal K. et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26 (07) 1017-1032
    CrossrefPubMedGoogle Scholar
  • 25 Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: a novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta 2020; 507: 167-173
    CrossrefPubMedGoogle Scholar
  • 26 Skurk T, Lee YM, Hauner H. Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture. Hypertension 2001; 37 (05) 1336-1340
    CrossrefPubMedGoogle Scholar
  • 27 Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res 2019; 181: 77-83
    CrossrefPubMedGoogle Scholar
  • 28 Chen X, Yang X, Zheng Y, Yang Y, Xing Y, Chen Z. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell 2014; 5 (05) 369-381
    CrossrefPubMedGoogle Scholar
  • 29 Siu KL, Kok KH, Ng MJ. et al. Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex. J Biol Chem 2009; 284 (24) 16202-16209
    CrossrefPubMedGoogle Scholar
  • 30 Voicu S, Ketfi C, Stépanian A. et al. Pathophysiological processes underlying the high prevalence of deep vein thrombosis in critically ill COVID-19 patients. Front Physiol 2021; 11: 608788
    CrossrefPubMedGoogle Scholar
  • 31 Favaloro EJ, Henry BM, Lippi G. Is lupus anticoagulant a significant feature of COVID-19? A critical appraisal of the literature. Semin Thromb Hemost 2022; 48 (01) 55-71
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Favaloro EJ, Henry BM, Lippi G. COVID-19 and antiphospholipid antibodies: time for a reality check?. Semin Thromb Hemost 2022; 48 (01) 72-92
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Helms J, Tacquard C, Severac F. et al; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020; 46 (06) 1089-1098
    CrossrefPubMedGoogle Scholar
  • 34 Llitjos JF, Leclerc M, Chochois C. et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020; 18 (07) 1743-1746
    CrossrefPubMedGoogle Scholar
  • 35 Nadkarni GN, Lala A, Bagiella E. et al. Anticoagulation, bleeding, mortality, and pathology in hospitalized patients with COVID-19. J Am Coll Cardiol 2020; 76 (16) 1815-1826
    CrossrefPubMedGoogle Scholar
  • 36 Ionescu F, Jaiyesimi I, Petrescu I. et al. Association of anticoagulation dose and survival in hospitalized COVID-19 patients: a retrospective propensity score-weighted analysis. Eur J Haematol 2021; 106 (02) 165-174
    CrossrefPubMedGoogle Scholar
  • 37 Lemos ACB, do Espírito Santo DA, Salvetti MC. et al. Therapeutic versus prophylactic anticoagulation for severe COVID-19: a randomized phase II clinical trial (HESACOVID). Thromb Res 2020; 196: 359-366
    CrossrefPubMedGoogle Scholar
  • 38 Goligher EC, Bradbury CA, McVerry BJ. et al; REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med 2021; 385 (09) 777-789
    CrossrefPubMedGoogle Scholar
  • 39 Sadeghipour P, Talasaz AH, Rashidi F. et al; INSPIRATION Investigators. Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION randomized clinical trial. JAMA 2021; 325 (16) 1620-1630
    CrossrefPubMedGoogle Scholar
  • 40 Perepu US, Chambers I, Wahab A. et al. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: a multi-center, open-label, randomized controlled trial. J Thromb Haemost 2021; 19 (09) 2225-2234
    CrossrefPubMedGoogle Scholar
  • 41 Spyropoulos AC, Goldin M, Giannis D. et al; HEP-COVID Investigators. Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern Med 2021; 181 (12) 1612-1620
    CrossrefPubMedGoogle Scholar
  • 42 Billett HH, Reyes-Gil M, Szymanski J. et al. Anticoagulation in COVID-19: effect of enoxaparin, heparin, and apixaban on mortality. Thromb Haemost 2020; 120 (12) 1691-1699
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Sholzberg M, Tang GH, Rahhal H. et al; RAPID trial investigators. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ 2021; 375: n2400
    CrossrefPubMedGoogle Scholar
  • 44 Lawler PR, Goligher EC, Berger JS. et al; ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med 2021; 385 (09) 790-802
    CrossrefPubMedGoogle Scholar
  • 45 Lopes RD, de Barros E Silva PGM, Furtado RHM. et al; ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021; 397 (10291): 2253-2263
    CrossrefPubMedGoogle Scholar
  • 46 Lindahl U, Li JP. Heparin - An old drug with multiple potential targets in Covid-19 therapy. J Thromb Haemost 2020; 18 (09) 2422-2424
    CrossrefPubMedGoogle Scholar
  • 47 Spyropoulos AC, Anderson Jr FA, FitzGerald G. et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011; 140 (03) 706-714
    CrossrefPubMedGoogle Scholar
  • 48 MacDougall K, Spyropoulos AC. New paradigms of extended thromboprophylaxis in medically ill patients. J Clin Med 2020; 9 (04) E1002
    CrossrefPubMedGoogle Scholar
  • 49 Giannis D, Allen SL, Tsang J. et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood 2021; 137 (20) 2838-2847
    CrossrefPubMedGoogle Scholar
  • 50 Roberts LN, Whyte MB, Georgiou L. et al. Postdischarge venous thromboembolism following hospital admission with COVID-19. Blood 2020; 136 (11) 1347-1350
    CrossrefPubMedGoogle Scholar
  • 51 Ramacciotti E, Barile Agati L, Calderaro D. et al; MICHELLE investigators. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet 2022; 399 (10319): 50-59
    CrossrefPubMedGoogle Scholar
  • 52 Piazza G, Campia U, Hurwitz S. et al. Registry of arterial and venous thromboembolic complications in patients with COVID-19. J Am Coll Cardiol 2020; 76 (18) 2060-2072
    CrossrefPubMedGoogle Scholar
  • 53 Connors JM, Brooks MM, Sciurba FC. et al; ACTIV-4B Investigators. Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID-19: the ACTIV-4B randomized clinical trial. JAMA 2021; 326 (17) 1703-1712
    CrossrefPubMedGoogle Scholar
  • 54 Ananworanich J, Mogg R, Dunne MW. et al. Randomized study of rivaroxaban vs. placebo on disease progression and symptoms resolution in high-risk adults with mild COVID-19. Clin Infect Dis 2022; 75 (01) e473-e481
    CrossrefPubMedGoogle Scholar
  • 55 Capell WH, Barnathan ES, Piazza G. et al. Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: the PREVENT-HD study. Am Heart J 2021; 235: 12-23
    CrossrefPubMedGoogle Scholar
  • 56 Rizk JG, Lippi G, Rizk Y. Thromboprophylaxis in outpatients with COVID-19: a safe bet or tilting at windmills?. Minerva Cardiol Angiol 2022; 70 (01) 1-4
    PubMedGoogle Scholar
  • 57 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton III LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143 (10) 697-706
    CrossrefPubMedGoogle Scholar
  • 58 Breslin N, Baptiste C, Gyamfi-Bannerman C. et al. Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol MFM 2020; 2 (02) 100118
    CrossrefPubMedGoogle Scholar
  • 59 Knight M, Bunch K, Vousden N. et al; UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 2020; 369: m2107
    CrossrefPubMedGoogle Scholar
  • 60 Delahoy MJ, Whitaker M, O'Halloran A. et al; COVID-NET Surveillance Team. Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (38) 1347-1354
    CrossrefPubMedGoogle Scholar
  • 61 COVID-19 FAQs for Obstetrician-Gynecologists. Obstetrics. Accessed January 3, 2022 at: https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics
    PubMedGoogle Scholar
  • 62 ACOG Practice Bulletin No. ACOG Practice Bulletin No. 196 Summary: Thromboembolism in Pregnancy. Obstet Gynecol 2018; 132 (01) 243-248
    CrossrefPubMedGoogle Scholar
  • 63 Antithrombotic Therapy in Patients With COVID-19. Accessed February 10, 2022 at: https://www.covid19treatmentguidelines.nih.gov/therapies/antithrombotic-therapy/
    PubMedGoogle Scholar
  • 64 Bates SM, Rajasekhar A, Middeldorp S. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22) 3317-3359
    CrossrefPubMedGoogle Scholar
  • 65 Abani O, Abbas A, Abbas F. et al; RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2022; 399 (10320): 143-151
    CrossrefPubMedGoogle Scholar
  • 66 Rizk JG, Lavie CJ, Gupta A. Low-dose aspirin for early COVID-19: does the early bird catch the worm?. Expert Opin Investig Drugs 2021; 30 (08) 785-788
    CrossrefPubMedGoogle Scholar
  • 67 Srivastava R, Kumar A. Use of aspirin in reduction of mortality of COVID-19 patients: a meta-analysis. Int J Clin Pract 2021; 75 (11) e14515
    CrossrefPubMedGoogle Scholar
  • 68 Martha JW, Pranata R, Lim MA, Wibowo A, Akbar MR. Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: a systematic review and meta-analysis of adjusted effect estimates. Int J Infect Dis 2021; 108: 6-12
    CrossrefPubMedGoogle Scholar
  • 69 Berger JS, Kornblith LZ, Gong MN. et al; ACTIV-4a Investigators. Effect of P2Y12 inhibitors on survival free of organ support among non-critically ill hospitalized patients with COVID-19: a randomized clinical trial. JAMA 2022; 327 (03) 227-236
    CrossrefPubMedGoogle Scholar
  • 70 Moores LK, Tritschler T, Brosnahan S. et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST Guideline and Expert Panel Report. Chest 2020; 158 (03) 1143-1163
    CrossrefPubMedGoogle Scholar
  • 71 Leentjens J, van Haaps TF, Wessels PF, Schutgens REG, Middeldorp S. COVID-19-associated coagulopathy and antithrombotic agents-lessons after 1 year. Lancet Haematol 2021; 8 (07) e524-e533
    CrossrefPubMedGoogle Scholar
  • 72 Andreozzi GM, Bignamini AA, Davì G. et al; SURVET Study Investigators. Sulodexide for the prevention of recurrent venous thromboembolism: the Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) study: a multicenter, randomized, double-blind, placebo-controlled trial. Circulation 2015; 132 (20) 1891-1897
    CrossrefPubMedGoogle Scholar
  • 73 COVID-19 and VTE/Anticoagulation: Frequently Asked Questions. Accessed January 5, 2022 at: https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation
    PubMedGoogle Scholar
  • 74 COVID-19 and Thrombosis Prevention. Accessed January 4, 2022 at: https://www.acc.org/latest-in-cardiology/articles/2021/08/31/12/21/covid-19-and-thrombosis-prevention
    PubMedGoogle Scholar
  • 75 Spyropoulos AC, Levy JH, Ageno W. et al; Subcommittee on Perioperative, Critical Care Thrombosis, Haemostasis of the Scientific, Standardization Committee of the International Society on Thrombosis and Haemostasis. Scientific and Standardization Committee communication: clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18 (08) 1859-1865
    CrossrefPubMedGoogle Scholar
  • 76 Tree JA, Turnbull JE, Buttigieg KR. et al. Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. Br J Pharmacol 2021; 178 (03) 626-635
    CrossrefPubMedGoogle Scholar
  • 77 Rizk J, Mehra MR. Anticoagulation management strategies in heart transplantation. Prog Cardiovasc Dis 2020; 63 (03) 210-218
    CrossrefPubMedGoogle Scholar
  • 78 Spyropoulos AC, Lipardi C, Xu J. 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 (01) e59-e65
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Cohen AT, Spiro TE, Büller HR. et al; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368 (06) 513-523
    CrossrefPubMedGoogle Scholar
  • 80 Hull RD, Schellong SM, Tapson VF. et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153 (01) 8-18
    CrossrefPubMedGoogle Scholar
  • 81 Rizk JG, Gupta A, Sardar P. et al. Clinical characteristics and pharmacological management of COVID-19 vaccine-induced immune thrombotic thrombocytopenia with cerebral venous sinus thrombosis: a review. JAMA Cardiol 2021; 6 (12) 1451-1460
    CrossrefPubMedGoogle Scholar
  • 82 Rizk JG, Barr CE, Rizk Y, Lewin JC. The next frontier in vaccine safety and VAERS: lessons from COVID-19 and ten recommendations for action. Vaccine 2021; 39 (41) 6017-6018
    CrossrefPubMedGoogle Scholar
  • 83 Langer F, Kluge S, Klamroth R, Oldenburg J. Coagulopathy in COVID-19 and its implication for safe and efficacious thromboprophylaxis. Hamostaseologie 2020; 40 (03) 264-269
    Article in Thieme ConnectPubMedGoogle Scholar
  • 84 Cuker A, Tseng EK, Nieuwlaat R. et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: July 2021 update on postdischarge thromboprophylaxis. Blood Adv 2022; 6 (02) 664-671
    CrossrefPubMedGoogle Scholar
  • 85 WHO. COVID-19 clinical management: living guidance. Nov 23, 2021. Accessed February 27, 2022 at: https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-clinical-2021-2
    PubMedGoogle Scholar
  • 86 Wichmann D, Sperhake JP, Lütgehetmann M. et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020; 173 (04) 268-277
    CrossrefPubMedGoogle Scholar