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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(02): 186-191
DOI: 10.1055/a-1956-9641
Review Article

Knowledge Gaps for Prophylactic Use of Antithrombotic Agents in Patients with COVID-19: Insights into New SARS-CoV-2 Variants, Vaccination Status, and Emerging Oral Antivirals

Azita H. Talasaz 
1   Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2   Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, Virginia, United States
,
Parham Sadeghipour 
3   Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
4   Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Kasra Mehdizadeh
3   Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Niloofar Khoshnam Rad
1   Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
Behnood Bikdeli
5   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
6   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
7   Yale/YNHH Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut, United States
8   Cardiovascular Research Foundation (CRF), New York, New York, United States
,
Gregory Y. H. Lip 
9   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
10   Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
,
Job Harenberg
11   Ruprecht Karls University, Heidelberg, Germany
12   Ruperto Carola University of Heidelberg, Heidelberg, Germany
› Institutsangaben Funding Dr. B.B. is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital and a Career Development Award from the American Heart Association and VIVA Physicians (#938814).
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Abstract

Data suggest that coronavirus disease 2019 (COVID-19) results in a prothrombotic state leading to arterial and venous thromboses. Vaccination, novel antiviral drugs, and emerging variants have changed the course of the disease in many ways; however, their effects on the incidence of thrombotic events and the efficacy of preventative antithrombotic agents have not been yet evaluated. A systematic search was conducted to identify studies reported on the incidence of thrombotic events based on vaccination status, use of novel antiviral drugs, and emerging viral variants. Similarly, we screened the ongoing/published randomized trials of preventative antithrombotic therapy in any COVID-19 population to assess whether subgroup-specific results were reported based on any of these variants. Upon searching a total of 3,451 records, only one entry fulfilled the inclusion criteria of our systematic review, which was a self-controlled case series on 29,121,633 vaccinated individuals, the incidence rate ratio of thrombotic complication after breakthrough infection was 13.86 (95% confidence interval [CI]: 12.76–15.05) compared with 1.10 (95% CI: 1.02–1.18) during the 28-day postvaccination. In conclusion, although the mortality benefit of mass vaccination and the early promising results of the new antiviral therapies are well known, we were unable to find clinical evidence on whether vaccination, the use of novel antiviral agents, and emerging viral variants have affected the incidence rate of thrombotic events or impacted the efficacy of prophylactic antithrombotic therapy in patients with COVID-19. Analyses from existing trials and large-scale registries can provide interim knowledge and any findings of relevance should be incorporated in the design of future trials.

Keywords

thromboembolism - anticoagulation - SARS-CoV-2 - vaccination - COVID-19

Disclosures

Dr. B.B. reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters.


Dr G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally.


Dr J.H.: founder and managing director of DOASENSE GmbH.


All other authors report no relevant disclosures.


Note: The review process for this paper was fully handled by Christian Weber, Editor-in-Chief.


Supplementary Material



Publikationsverlauf

Eingereicht: 07. Juni 2022

Angenommen: 20. August 2022

Accepted Manuscript online:
07. Oktober 2022

Artikel online veröffentlicht:
30. Dezember 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
    CrossrefPubMedGoogle Scholar
  • 2 Barale C, Melchionda E, Morotti A, Russo I. Prothrombotic phenotype in COVID-19: focus on platelets. Int J Mol Sci 2021; 22 (24) 13638
    CrossrefPubMedGoogle Scholar
  • 3 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
  • 4 McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol 2020; 2 (07) e437-e445
    CrossrefPubMedGoogle Scholar
  • 5 Lu YF, Pan LY, Zhang W-W. et al. A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19. Int J Infect Dis 2020; 100: 34-41
    CrossrefPubMedGoogle Scholar
  • 6 Talasaz AH, Sadeghipour P, Kakavand H. et al. Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC state-of-the-art review. J Am Coll Cardiol 2021; 77 (15) 1903-1921
    CrossrefPubMedGoogle Scholar
  • 7 Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18 (05) 1094-1099
    CrossrefPubMedGoogle Scholar
  • 8 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
  • 9 Paranjpe I, Fuster V, Lala A. et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 2020; 76 (01) 122-124
    CrossrefPubMedGoogle Scholar
  • 10 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
    Google Scholar
  • 11 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
    Google Scholar
  • 12 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
  • 13 Al Kaabi N, Zhang Y, Xia S. et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 2021; 326 (01) 35-45
    CrossrefPubMedGoogle Scholar
  • 14 Tenforde MW, Self WH, Adams K. et al; Influenza and Other Viruses in the Acutely Ill (IVY) Network. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA 2021; 326 (20) 2043-2054
    CrossrefPubMedGoogle Scholar
  • 15 Wang Z, Yang L. In the age of Omicron variant: Paxlovid raises new hopes of COVID-19 recovery. J Med Virol 2022; 94 (05) 1766-1767
    CrossrefPubMedGoogle Scholar
  • 16 Caraco Y, Crofoot GE, Moncada PA. et al. Phase 2/3 trial of molnupiravir for treatment of Covid-19 in nonhospitalized adults. NEJM Evid 2021; 1 (02) DOI: 10.1056/EVIDoa2100043.
    CrossrefPubMedGoogle Scholar
  • 17 Tian D, Sun Y, Zhou J, Ye Q. The global epidemic of the SARS-CoV-2 delta variant, key spike mutations and immune escape. Front Immunol 2021; 12: 751778
    CrossrefPubMedGoogle Scholar
  • 18 Abdullah F, Myers J, Basu D. et al. Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in Tshwane, South Africa. Int J Infect Dis 2022; 116: 38-42
    CrossrefPubMedGoogle Scholar
  • 19 Hippisley-Cox J, Patone M, Mei XW. et al. Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ 2021; 374: n1931
    CrossrefPubMedGoogle Scholar
  • 20 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
  • 21 Sadarangani M, Marchant A, Kollmann TR. Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol 2021; 21 (08) 475-484
    CrossrefPubMedGoogle Scholar
  • 22 Haas EJ, Angulo FJ, McLaughlin JM. et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet 2021; 397 (10287): 1819-1829
    CrossrefPubMedGoogle Scholar
  • 23 Bahl A, Johnson S, Maine G. et al. Vaccination reduces need for emergency care in breakthrough COVID-19 infections: a multicenter cohort study. Lancet Reg Health Am 2021; 4: 100065
    PubMedGoogle Scholar
  • 24 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
  • 25 Cines DB, Bussel JB. SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. N Engl J Med 2021; 384 (23) 2254-2256
    CrossrefPubMedGoogle Scholar
  • 26 Kim YE, Huh K, Park YJ, Peck KR, Jung J. Association between vaccination and acute myocardial infarction and ischemic stroke after COVID-19 infection. JAMA 2022; 328 (09) 887-889
    CrossrefPubMedGoogle Scholar
  • 27 Law N, Chan J, Kelly C, Auffermann WF, Dunn DP. Incidence of pulmonary embolism in COVID-19 infection in the ED: ancestral, Delta, Omicron variants and vaccines. Emerg Radiol 2022; 29 (04) 625-629
    CrossrefPubMedGoogle Scholar
  • 28 Tao K, Tzou PL, Nouhin J. et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet 2021; 22 (12) 757-773
    CrossrefPubMedGoogle Scholar
  • 29 Durand M, Sinyavskaya L, Jin YL, Tremblay CL, Ducruet T, Laskine M. Incidence of venous thromboembolism in patients living with HIV: a cohort study. AIDS Patient Care STDS 2019; 33 (11) 455-458
    CrossrefPubMedGoogle Scholar
  • 30 Matta F, Yaekoub AY, Stein PD. Human immunodeficiency virus infection and risk of venous thromboembolism. Am J Med Sci 2008; 336 (05) 402-406
    CrossrefPubMedGoogle Scholar
  • 31 Bibas M, Biava G, Antinori A. HIV infection as a permanent, acquired risk factor for VTE. Nat Rev Cardiol 2014; 11 (06) 321
    CrossrefPubMedGoogle Scholar
  • 32 Mahase E. Covid-19: Pfizer's paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ 2021; 375 (2713): n2713
    CrossrefPubMedGoogle Scholar
  • 33 Jayk Bernal A, Gomes da Silva MM, Musungaie DB. et al; MOVe-OUT Study Group. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med 2022; 386 (06) 509-520
    CrossrefPubMedGoogle Scholar
  • 34 Bikdeli B, Madhavan MV, Jimenez D. et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
    CrossrefPubMedGoogle Scholar
  • 35 Kyriakoulis KG, Kollias A, Kyriakoulis IG. et al. Thromboprophylaxis in patients with COVID-19: systematic review of National and International Clinical Guidance reports. Curr Vasc Pharmacol 2022; 20 (01) 96-110
    CrossrefPubMedGoogle Scholar
  • 36 Gerotziafas GT, Catalano M, Colgan MP. et al; Scientific Reviewer Committee. Guidance for the management of patients with vascular disease or cardiovascular risk factors and COVID-19: position paper from VAS-European Independent Foundation in Angiology/Vascular Medicine. Thromb Haemost 2020; 120 (12) 1597-1628
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 37 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
  • 38 Barnes GD, Burnett A, Allen A. et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020; 50 (01) 72-81
    CrossrefPubMedGoogle Scholar
  • 39 Cuker A, Tseng EK, Nieuwlaat R. et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv 2021; 5 (03) 872-888
    CrossrefPubMedGoogle Scholar
  • 40 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
  • 41 van de Veerdonk FL, Giamarellos-Bourboulis E, Pickkers P. et al. A guide to immunotherapy for COVID-19. Nat Med 2022; 28 (01) 39-50
    CrossrefPubMedGoogle Scholar
  • 42 Alexander PE, Armstrong R, Fareed G. et al. Early multidrug treatment of SARS-CoV-2 infection (COVID-19) and reduced mortality among nursing home (or outpatient/ambulatory) residents. Med Hypotheses 2021; 153: 110622
    CrossrefPubMedGoogle Scholar
  • 43 Wen W, Chen C, Tang J. et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19:a meta-analysis. Ann Med 2022; 54 (01) 516-523
    CrossrefPubMedGoogle Scholar
  • 44 Davidson M, Menon S, Chaimani A. et al. Interleukin-1 blocking agents for treating COVID-19. Cochrane Database Syst Rev 2022; 1 (01) CD015308
    CrossrefPubMedGoogle Scholar
  • 45 Munblit D, Nicholson TR, Needham DM. et al. Studying the post-COVID-19 condition: research challenges, strategies, and importance of Core Outcome Set development. BMC Med 2022; 20 (01) 50
    CrossrefPubMedGoogle Scholar