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DOI: 10.1055/s-0042-1746420
Letter to the Editor: Venous Thromboembolism in COVID-19: Are Women Different?

I read with interest the article[1] about therapeutic anticoagulation in patients with coronavirus disease 2019 (COVID-19) and considerations in women. I applaud the authors for performing rigorous review to address this important clinical concern in COVID-19. High prevalence of venous thromboembolism (VTE) was observed in 22.7% of patients in intensive care units.[2] Observational studies and initial autopsy series showed high rates of both venous and arterial thrombosis as well as prominent pulmonary microvascular thrombosis. Patients with COVID-19 were reported to have 6% more risk to develop VTE as compared to non-COVID-19 patients.[3] In addition, COVID-19-associated coagulopathy was recognized as a marker of disease severity and poor prognosis.
Contrasting results have been reported about the preferred anticoagulation therapy in patients with COVID-19 infection. As evident in the given article,[1] the recommendations by various societies and guidelines kept on changing as the evidence emerged. Elevated D-dimer levels were reported as predictive for breakthrough thrombosis[4] despite standard deep vein thrombosis prophylaxis. Some institutions started risk-stratifying patients for VTE based on the D-dimer cutoff points and started intermediate-dose prophylaxis in critically ill patients with COVID-19.[5] Follow-up studies have confirmed significant coagulopathy associated with severe COVID-19, characterized by marked elevation of fibrinogen, von Willebrand factor, and platelet and profound endothelia activation, but did not confirm predictive value for D-dimer as marker of thrombotic risk. Multicenter randomized trial refuted the benefit of intermediate-dose prophylaxis in changing outcomes in terms of incidence of VTE, treatment with extracorporeal membrane oxygenation, or 30-day mortality.[6]
Later retrospective studies suggested mortality benefit of therapeutic anticoagulation for critically ill patients, particularly those requiring mechanical ventilation.[7] In a randomized controlled trial, therapeutic anticoagulation resulted in improved gas exchange, decreased D-dimer, and higher prevalence of liberation from mechanical ventilation.[8] The two recent international, adaptive, multiplatform, randomized, controlled trials studied the effectiveness and safety of use of therapeutic-dose heparin or low-molecular-weight heparin in this patient population.[9] [10] The main findings were that therapeutic-dose heparin or low-molecular-weight heparin reduced mortality among patients with moderate infection but not among those with severe infection. A possible explanation for this difference could be that when infection reaches its severe state, the damage surpasses the reversibility by anticoagulation.
The article methodically outlines the higher predilection of VTE in male population attributing to variant involvement of angiotensin converting enzyme-2. The current National Institutes of Health guidelines recommend prophylactic-dose anticoagulation for pregnant hospitalized patients. Because pregnant females were not included in most clinical trials, there is insufficient evidence either for or against therapeutic anticoagulation.
Trials to evaluate platelet inhibition, therapeutic interventions targeting the endothelium, and platelet activation as well as outpatient anticoagulation strategies are ongoing.
Publication History
Article published online:
29 July 2022
© 2022. Women in Cardiology and Related Sciences. 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 Chhabra ST, Goyal P. Venous thromboembolism in COVID-19: are women different?. Indian J Cardiovasc Dis Women WINCARS 2020; 5 (03) 200-208
- 2 Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID-19: a systematic review and meta-analysis. Res Pract Thromb Haemost 2020; 4 (07) 1178-1191
- 3 Tufano A, Rendina D, Abate V. et al. Venous thromboembolism in covid-19 compared to non-covid-19 cohorts: a systematic review with meta-analysis. J Clin Med 2021; 10 (21) 4925 DOI: 10.3390/jcm10214925.
- 4 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
- 5 Choi JJ, Wehmeyer GT, Li HA. et al. D-dimer cut-off points and risk of venous thromboembolism in adult hospitalized patients with COVID-19. Thromb Res 2020; 196 (August): 318-321
- 6 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
- 7 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
- 8 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 (January): 359-366
- 9 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
- 10 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