Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study

doi:10.1016/j.jsps.2022.01.022

. 2022 Apr;30(4):398-406.

doi: 10.1016/j.jsps.2022.01.022. Epub 2022 Feb 3.

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study

Ohoud Aljuhani¹, Khalid Al Sulaiman^{2

3

4}, Awatif Hafiz¹, Khalid Eljaaly^{1

5}, Aisha Alharbi⁶, Rahmah Algarni⁶, Sarah Al Homaid³, Khawla Kahtani³, Tareq Alsulaiman⁷, Ramesh Vishwakarma⁸, Ghassan Al Ghamdi^{4

9

10}, Mai Alalawi¹¹, Ghazwa B Korayem¹²

Affiliations

¹ Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
² Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
³ College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
⁴ King Abdullah International Medical Research Center, Biostatistics and Bioinformatics Department, Riyadh, Saudi Arabia.
⁵ College of Pharmacy, University of Arizona, Tucson, AZ, United States.
⁶ Pharmaceutical Care Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
⁷ Department of Orthopedic Surgery, Imam Abdulrahman Al Faisal Hospital, Riyadh, Saudi Arabia.
⁸ Statistics Department, European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
⁹ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Saudi Arabia.
¹⁰ Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
¹¹ Fakeeh College of Medical Sciences, Jeddah, Saudi Arabia.
¹² Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

PMID: 35136364
PMCID: PMC8812085
DOI: 10.1016/j.jsps.2022.01.022

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study

Ohoud Aljuhani et al. Saudi Pharm J. 2022 Apr.

. 2022 Apr;30(4):398-406.

doi: 10.1016/j.jsps.2022.01.022. Epub 2022 Feb 3.

Authors

Affiliations

¹ Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
² Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
³ College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
⁴ King Abdullah International Medical Research Center, Biostatistics and Bioinformatics Department, Riyadh, Saudi Arabia.
⁵ College of Pharmacy, University of Arizona, Tucson, AZ, United States.
⁶ Pharmaceutical Care Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
⁷ Department of Orthopedic Surgery, Imam Abdulrahman Al Faisal Hospital, Riyadh, Saudi Arabia.
⁸ Statistics Department, European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
⁹ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Saudi Arabia.
¹⁰ Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
¹¹ Fakeeh College of Medical Sciences, Jeddah, Saudi Arabia.
¹² Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

PMID: 35136364
PMCID: PMC8812085
DOI: 10.1016/j.jsps.2022.01.022

Abstract

Introduction: The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19.

Methods: A two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the "standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under "escalated VTE prophylaxis dose". The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications.

Results: A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52-2.86; P = 0.64 and OR 0.75; 95% CI 0.16-3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79-1.73; P = 0.43 and HR 1.08;95 %CI 0.76-1.53; P = 0.83, respectively).

Conclusion: Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.

Keywords: COVID-19; COVID-19, Coronavirus disease; Critically ill; Enoxaparin; Escalated-dose; Heparin; ICUs, Intensive care units; Intensive Care Units (ICUs); LOS, Length of Stay; MV, Mechanical ventilation; SARS-Cov-2; Standard dose; VTE prophylaxis; VTE, Venous thromboembolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Flowchart of adult patients admitted to the intensive care unit (ICU) with confirmed COVID-19.

**Fig. 2a**
Kaplan Meier Curve for overall survival comparing the escalated "High" dose and standard dosing of VTE prophylaxis during ICU stay - Before Propensity score matching.

**Fig. 2b**
Kaplan Meier Curve for overall survival comparing the escalated "High" dose and standard dosing of VTE prophylaxis during ICU stay - After Propensity score matching.

See this image and copyright information in PMC

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1. Barnes G.D., Burnett A., Allen A., Blumenstein M., Clark N.P., Cuker A., Dager W.E., Deitelzweig S.B., Ellsworth S., Garcia D., Kaatz S., Minichiello T. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J. Thromb. Thrombolysis. 2020;50:72–81. doi: 10.1007/s11239-020-02138-z. - DOI - PMC - PubMed

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[1] Abrams M.P., Wan E.Y., Waase M.P., Morrow J.P., Dizon J.M., Yarmohammadi H., Berman J.P., Rubin G.A., Kushnir A., Poterucha T.J., Elias P.A., Rubin D.A., Ehlert F., Biviano A., Uriel N., Garan H., Saluja D. Clinical and cardiac characteristics of COVID-19 mortalities in a diverse New York City Cohort. J. Cardiovasc. Electrophysiol. 2020;31 doi: 10.1111/jce.14772. - DOI - PMC - PubMed

[2] Abrams M.P., Wan E.Y., Waase M.P., Morrow J.P., Dizon J.M., Yarmohammadi H., Berman J.P., Rubin G.A., Kushnir A., Poterucha T.J., Elias P.A., Rubin D.A., Ehlert F., Biviano A., Uriel N., Garan H., Saluja D. Clinical and cardiac characteristics of COVID-19 mortalities in a diverse New York City Cohort. J. Cardiovasc. Electrophysiol. 2020;31 doi: 10.1111/jce.14772. - DOI - PMC - PubMed

[3] Al Sulaiman K.A., Aljuhani O., Eljaaly K., Alharbi A.A., al Shabasy A.M., Alsaeedi A.S., al Mutairi M., Badreldin H.A., al Harbi S.A., al Haji H.A., al Zumai O.I., Vishwakarma R.K., Alkatheri A. Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study. Int. J. Infectious Diseases. 2021;105:180–187. doi: 10.1016/j.ijid.2021.02.037. - DOI - PMC - PubMed

[4] Al Sulaiman K.A., Aljuhani O., Eljaaly K., Alharbi A.A., al Shabasy A.M., Alsaeedi A.S., al Mutairi M., Badreldin H.A., al Harbi S.A., al Haji H.A., al Zumai O.I., Vishwakarma R.K., Alkatheri A. Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study. Int. J. Infectious Diseases. 2021;105:180–187. doi: 10.1016/j.ijid.2021.02.037. - DOI - PMC - PubMed

[9] Barnes G.D., Burnett A., Allen A., Blumenstein M., Clark N.P., Cuker A., Dager W.E., Deitelzweig S.B., Ellsworth S., Garcia D., Kaatz S., Minichiello T. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J. Thromb. Thrombolysis. 2020;50:72–81. doi: 10.1007/s11239-020-02138-z. - DOI - PMC - PubMed

[10] Barnes G.D., Burnett A., Allen A., Blumenstein M., Clark N.P., Cuker A., Dager W.E., Deitelzweig S.B., Ellsworth S., Garcia D., Kaatz S., Minichiello T. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J. Thromb. Thrombolysis. 2020;50:72–81. doi: 10.1007/s11239-020-02138-z. - DOI - PMC - PubMed

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Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study

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Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study

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