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Pharmaceuticals 2018, 11(2), 46; https://doi.org/10.3390/ph11020046

The Effects of Dabigatran and Rivaroxaban on Markers of Polymorphonuclear Leukocyte Activation

1
Department of Critical Care, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
2
Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
3
Tshwane Academic Division of the National Health Laboratory Service of South Africa, Pretoria 0001, South Africa
4
Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
*
Author to whom correspondence should be addressed.
Received: 16 April 2018 / Revised: 3 May 2018 / Accepted: 4 May 2018 / Published: 14 May 2018
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Abstract

Dabigatran is an oral direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor. Dabigatran has been implicated in the etiology of acute coronary syndromes and as these occur following inflammatory changes in the endothelium, we investigated the inflammatory potential of these agents in vitro. In order to do so, polymorphonuclear leukocytes (PMNL) were isolated from heparinized venous blood from non-smoking, healthy adults and exposed to dabigatran or rivaroxaban (0.5–10 µM). Generation of reactive oxygen species (ROS), elastase release, cytosolic Ca2+ fluxes, neutrophil extracellular trap (NET) formation and cell viability were measured using chemiluminescence, spectrophotometric and flow cytometric procedures respectively. However, with the exception of modest inhibitory effects on elastase release, neither agent at concentrations of up to 10 µM affected these markers of PMNL activation. Although no pro-inflammatory effects of dabigatran nor any difference between the two test agents were detected in vitro, the existence of a pro-inflammatory mechanism involving the generation of thrombin during dabigatran therapy cannot be fully excluded. View Full-Text
Keywords: dabigatran; rivaroxaban; inflammation; ischemic heart disease; polymorphonuclear leukocytes dabigatran; rivaroxaban; inflammation; ischemic heart disease; polymorphonuclear leukocytes
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Richards, G.A.; Theron, A.; Tintinger, G.; Anderson, R. The Effects of Dabigatran and Rivaroxaban on Markers of Polymorphonuclear Leukocyte Activation. Pharmaceuticals 2018, 11, 46.

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