Effects of low molecular weight heparin and fondaparinux on mortality, hemorrhagic and thrombotic complications in COVID-19 patients

Paraskevi C Fragkou; Lina Palaiodimou; Maria Ioanna Stefanou; Aristeidis H Katsanos; Vaia Lambadiari; Dimitrios Paraskevis; Elisabeth Andreadou; Dimitra Dimopoulou; Christina Zompola; Panagiotis Ferentinos; Theodoros I Vassilakopoulos; Anastasia Kotanidou; Petros P Sfikakis; Sotirios Tsiodras; Georgios Tsivgoulis

doi:10.1177/17562864221099472

Effects of low molecular weight heparin and fondaparinux on mortality, hemorrhagic and thrombotic complications in COVID-19 patients

Ther Adv Neurol Disord. 2022 May 24:15:17562864221099472. doi: 10.1177/17562864221099472. eCollection 2022.

Authors

Paraskevi C Fragkou¹, Lina Palaiodimou², Maria Ioanna Stefanou², Aristeidis H Katsanos³, Vaia Lambadiari⁴, Dimitrios Paraskevis⁵, Elisabeth Andreadou⁶, Dimitra Dimopoulou⁷, Christina Zompola², Panagiotis Ferentinos⁸, Theodoros I Vassilakopoulos⁹, Anastasia Kotanidou¹, Petros P Sfikakis¹⁰, Sotirios Tsiodras¹¹, Georgios Tsivgoulis¹²

Affiliations

¹ First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece.
² Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece.
³ Division of Neurology, Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
⁴ Second Department of Internal Medicine Research Unit and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece.
⁵ Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
⁶ First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
⁷ Second Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, 'Panagiotis and Aglaia Kyriakou' Children's Hospital, Athens, Greece.
⁸ Second Department of Psychiatry, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece.
⁹ Third Department of Critical Care Medicine, School of Medicine, National and Kapodistrian University of Athens, Evgenideio Hospital, Athens, Greece.
¹⁰ First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹¹ Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece.
¹² Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Rimini 1, Chaidari, Athens 12462, Greece.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19.

Objective: We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases.

Design: We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients.

Data sources and methods: MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases.

Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19-3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses.

Conclusion: The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies.

Registration: The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

Keywords: COVID-19; SARS-CoV-2; fondaparinux; low molecular weight heparin; mortality.