Treatment with low-molecular-weight heparin has a beneficial effect on survival of COVID-19 patients and influences the duration of active infection, found a study from the Medical University of Vienna in Cardiovascular Research.
COVID-19 patients have an increased risk of thromboses and embolisms, such as strokes, pulmonary or myocardial infarctions, and even deep vein thromboses. The use of drugs that inhibit blood clotting has been part of the treatment guidelines for COVID-19 since July 2020.
“These complications during hospitalisation have a direct impact on the well-being of patients and increased the risk of dying from COVID-19,” reported David Pereyra from MedUni Vienna's Department of General Surgery, who is first author of the publication. The underlying coagulopathy is still not fully understood.
“The coagulopathy observed in COVID-19 patients is novel and differs in many respects from previously known coagulation problems,” said Alice Assinger, group leader at the Institute of Vascular Biology and Thrombosis Research at the Medical University of Vienna and last author of the publication. “COVID-19-associated coagulopathy displays characteristics that, although partially comparable with other coagulation diseases, cannot be fully explained by them.”
Assinger’s group therefore started to look for an explanation for this sub-condition of COVID-19 in the spring of 2020, in an early phase of the pandemic.
In a multi-centre analysis of COVID-19 patients in Vienna, Linz and Innsbruck, the group observed that COVID-19-associated coagulopathy occurs almost exclusively in patients requiring intensive care or in patients who die as a result of COVID-19.
Although anticoagulant drugs improve the survival of COVID-19 patients, they show no effect on immunological processes related to blood coagulation (immunothrombosis).
The analyses showed, however, that the period of active SARS-CoV-2 infection was curtailed in patients treated with low-molecular-weight heparin, the most commonly used anticoagulant.
“In patients who receive this drug, infection time is an average of four days shorter than in patients who are not treated with low-molecular-weight heparin. We were surprised to see that low-molecular-weight heparin might have a direct effect on coronavirus and its infectivity,” said Pereyra. Experimental data show that heparin can inhibit the ability of SARS-CoV-2 to bind to cells, thereby preventing them from being infected.
These observations were made in the context of a close collaboration between the three hospitals involved: the Favoriten Hospital in Vienna, the Innsbruck Regional Hospital Innsbruck, and the Johannes Kepler University Hospital in Linz , as well as through the active exchange between basic researchers and clinicians, underscoring the relevance of good cooperation during the COVID-19 pandemic for a better understanding of the disease and its treatment.
Study details
Low-molecular-weight heparin use in coronavirus disease 2019 is associated with curtailed viral persistence: a retrospective multicentre observational study.
David Pereyra, Stefan Heber, Waltraud C Schrottmaier, Jonas Santol, Anita Pirabe, Anna Schmuckenschlager, Kerstin Kammerer, Daphni Ammon, Thomas Sorz, Fabian Fritsch, Hubert Hayden, Erich Pawelka, Philipp Krüger, Benedikt Rumpf, Marianna T Traugott, Pia Glaser, Christa Firbas, Christian Schörgenhofer, Tamara Seitz, Mario Karolyi, Ingrid Pabinger, Christine Brostjan, Patrick Starlinger, Günter Weiss, Rosa Bellmann-Weiler, Helmut J F Salzer, Bernd Jilma, Alexander Zoufaly, Alice Assinger.
Published in Cardiovascular Research on 5 October 2021
Abstract
Aims
Anticoagulation was associated with improved survival of hospitalised coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence.
Methods and results
Data of 586 hospitalised COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalisation. Plasma was collected at different time points in a subset of 106 patients to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348–0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalisation, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6–24) vs. 9 (interquartile range: 5–16) days, P = 0.009].
Conclusion
Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.
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