Use of DPP-4 inhibitors in patients with COVID-19
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LETTER TO THE EDITOR
Use of DPP‑4 inhibitors in patients with COVID‑19 Chia Siang Kow1 · Syed Shahzad Hasan2,3 Received: 27 August 2020 / Accepted: 29 October 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
We read with interest the discussion by Solerte et al. [1] on the various physiological processes on the immune system where dipeptidyl peptidase‐4 (DPP‐4) is involved. Besides, as hypothesized by the authors, the presence of DPP-4 in the respiratory tract may facilitate the entry of severe acute respiratory syndrome (SARS-CoV-2), the causative pathogen for coronavirus disease 2019 (COVID-19). Therefore, at first sight, it seems logical for the authors to propose that the use of DPP-4 inhibitors may be benficial in patients with COVID-19. However, as the pathophysiology of COVID-19 being unraveled, we have now acknowledged the potential for a substantial number of patients with COVID-19 to be complicated by the development of venous thromboembolism, especially those admitted into intensive care units. To illustrate, despite the initiation of pharmacological thromboprophylaxis, 31% of patients with COVID-19 admitted into intensive care units still developed venous thromboembolic events [2]. Indeed, COVID-19 has now been recognized as a hypercoagulable state where the elevation of several circulating prothrombotic factors had been reported [3]. Therefore, we should be very careful to call on for DPP-4 inhibitors to be repurposed as one of the treatment options for patients with COVID-19 since DPP-4 inhibitors have the potential to induce a prothrombic state. Other than their actions on glucose homeostasis and immune homeostasis, This comment refers to the article available online at https://doi. org/10.1007/s00592-020-01539-z. Managed by Massimo Porta * Chia Siang Kow [email protected] 1
School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
2
Department of Pharmacy, University of Huddersfield, Huddersfield, United Kingdom
3
School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, Australia
DPP-4 also acts on the vascular system where it possesses anti-thrombotic properties and may act as an immobilized anticoagulant on endothelial cells. This is owing to their ability to inhibit fibrin polymerization and clot formation. In vivo model has demonstrated a reduction in the expression and activity of DPP-4 within the infarction area of patients with acute myocardial infarction, which corresponded to an increase in pro-coagulant Tissue Factor expression, suggesting a shift toward a prothrombogenic status [4]. Furthermore, when human umbilical vein endothelial cells were treated with diprotin A which inhibits the activity of DPP-4, increased adherence of non-stimulated platelets under flow conditions was observed, corresponding to a sign of thrombogenicity [4]. Real-world data have also indicated a safety signal with DPP-4 inhibitors due to the increased reporting of venous thromboembolism events. A recent pharmacovigi
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