Background: Management of anticoagulant therapy in COVID-19 patients is critical. Low-molecular-weight heparin (LMWH) thromboprophylaxis is already recommended, and anti-Factor Xa (anti-FXa) monitoring has been used to titrate LMWH doses. Methods: Through a cross-sectional study, we evaluated anti-FXa activity in patients admitted to the ICU, receiving intermediate dose (30, 40, 50 mg, subcutaneously [SC], twice daily) or therapeutic dose (1 mg/kg, SC, Q12h) of enoxaparin to find whether the patients in these two groups achieved anti-FXa levels in the accepted thromboprophylaxis range. Results: The occurrence of deep vein thrombosis was 26% in the therapeutic-dose group and 17% in the intermediate-dose group. D-dimer values were nearly 3.5-fold higher in those who received a therapeutic dose of anticoagulants than in those who received intermediate-dose thromboprophylaxis. Patients in the therapeutic-dose group had significantly higher IL-6 levels (p ≤ 0.001). More than one-third of the patients in the therapeutic-dose group (n = 8; 42.18%) and approximately half of the patients in the intermediate-dose group (n = 12; 52.2%) achieved the target range level of anti-FXa. Patients who received therapeutic doses were more likely to have anti-FXa levels above the expected range (47.4 vs 13% in the intermediate-dose group; p < 0.05). Conclusion: Therapeutic dose of enoxaparin in critically ill COVID-19-infected patients did not reduce the incidence of thromboembolic events and, on the other hand, may predispose these patients to increased risk of bleeding by increasing anti-FXa activity above the desired level. Administration of intermediate-dose thromboprophylaxis is suggested to achieve anti-FXa levels in the accepted thromboprophylaxis range.

Keywords:
Coronavirus disease, Venous thromboembolism, Thromboprophylaxis, Anti-FXa activity
1.
Carfora V, Spiniello G, Ricciolino R, Di Mauro M, Migliaccio MG, Mottola FF, et al. Anticoagulant treatment in COVID-19: a narrative review. J Thromb Thrombolysis. 2021;51(3):642–8.
2.
Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18(5):1023–6.
3.
Bikdeli B, Madhavan MV, Gupta A, Jimenez D, Burton JR, Der Nigoghossian C, et al. Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research. Thromb Haemost. 2020;120(7):1004–24.
4.
Dutt T, Simcox D, Downey C, McLenaghan D, King C, Gautam M, et al. Thromboprophylaxis in COVID-19: anti-FXa–the missing factor? Am J Respir Crit Care Med. 2020;202(3):455–7.
5.
Rappaport SH, Clark JM, Delibert S, Maynard KM, Prasad P, Kaufman DC, et al. Anti-FXa activity with intermediate-dose thromboprophylaxis in COVID-19. Am J Respir Crit Care Med. 2020;202(12):1731–3.
6.
Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18(8):1995–2002.
7.
Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: may 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients. Blood Adv. 2021;5(20):3951–9.
8.
Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemost. 2020;120(5):876–8.
9.
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(4):844–7.
10.
Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis. 2020;50(1):72–81.
11.
Hamilton DO, Main-Ian A, Tebbutt J, Thrasher M, Waite A, Welters I. Standard-versus intermediate-dose enoxaparin for anti-factor Xa guided thromboprophylaxis in critically ill patients with COVID-19. Thromb J. 2021;19(1):87–5.
12.
INSPIRATION Investigators; Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, et al. 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):1620–30.
13.
Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020;127:104362.
14.
Spyropoulos AC, Goldin M, Giannis D, Diab W, Wang J, Khanijo S, et al. 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):1612–20.
15.
REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators, Goligher EC, Bradbury CA, et al. . Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med. 2021;385(9):777–89.
16.
Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med. 2006;144(9):673–84.
17.
Desborough MJ, Doyle AJ, Griffiths A, Retter A, Breen KA, Hunt BJ. Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom. Thromb Res. 2020;193:1–4.
18.
Fraissé M, Logre E, Pajot O, Mentec H, Plantefève G, Contou D. Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Crit Care. 2020;24(1):275–4.
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