Anti-inflammatory and Antiplatelet Effects of Non-vitamin K Antagonist Oral Anticoagulants in Acute Phase of Ischemic Stroke Patients

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2018 Jan 17

PMID 29335786

Citations 14

Authors

Taizen Nakase

Junta Moroi

Tatsuya Ishikawa

Affiliations

Soon will be listed here.

Abstract

Background: Recently, non-vitamin K antagonist oral anticoagulants such as direct thrombin and direct factor Xa inhibitors have been prescribed for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients. This study aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in the clinical setting of acute ischemic stroke.

Methods: Acute ischemic stroke patients newly prescribed anti-thrombotic agents were consecutively screened, and 44 patients with single medicine were enrolled (median 72.0 years-old). Blood samples were obtained at 1 and 2 weeks after the medication started. The extent of anticoagulation activity, inflammatory markers and platelet aggregation were assessed. Patients with antiplatelets were used as control.

Results: Prescribed antithrombotics were dabigatran (group D: n = 12), apixaban (group A: n = 14) and antiplatelet agents (group P: n = 18). Prevalence of stroke risks and anticoagulation activity were not different between groups D and A. The alteration of inflammatory markers in a week in the group A showed similar trend to those in the group P. The group D presented relatively lower amount of high-sensitive C-reactive protein and higher amount of pentraxin-3 compared with groups A and P. While 88.9% of group P patients showed decreased platelet aggregation activity with adenosine diphosphate, 55.6% of group D and 40.0% of group A presented the inhibition of platelet aggregation activity.

Conclusions: Even in acute ischemic stroke patients, both apixaban and dabigatran equally showed the anticoagulation activity. The reduction of inflammatory response might be prominent in apixaban, whereas the inhibition of platelet aggregation activity might be evident in dabigatran.

Citing Articles

Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation.

Berbers R, Paganelli F, van Montfrans J, Ellerbroek P, Viveen M, Rogers M Microbiome. 2025; 13(1):12.

PMID: 39819634 PMC: 11740714. DOI: 10.1186/s40168-024-01982-y.

Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate.

He Q, Wei Y, Qian Y, Zhong M J Intensive Med. 2024; 4(4):453-467.

PMID: 39310056 PMC: 11411436. DOI: 10.1016/j.jointm.2024.02.003.

Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.

Jannati S, Patnaik R, Banerjee Y Int J Mol Sci. 2024; 25(16).

PMID: 39201414 PMC: 11355043. DOI: 10.3390/ijms25168727.

Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.

Muric M, Nikolic M, Todorovic A, Jakovljevic V, Vucicevic K Biomolecules. 2024; 14(8).

PMID: 39199344 PMC: 11352257. DOI: 10.3390/biom14080956.

Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy.

Russo V, Falco L, Tessitore V, Mauriello A, Catapano D, Napolitano N Life (Basel). 2023; 13(9).

PMID: 37763292 PMC: 10532829. DOI: 10.3390/life13091888.

References

Cannon C, Bhatt D, Oldgren J, Lip G, Ellis S, Kimura T . Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017; 377(16):1513-1524. DOI: 10.1056/NEJMoa1708454. View

Esmon C . Targeting factor Xa and thrombin: impact on coagulation and beyond. Thromb Haemost. 2013; 111(4):625-33. DOI: 10.1160/TH13-09-0730. View

Wong P, Jiang X . Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombin. Thromb Haemost. 2010; 104(2):302-10. DOI: 10.1160/TH10-02-0097. View

Pingel S, Tiyerili V, Mueller J, Werner N, Nickenig G, Mueller C . Thrombin inhibition by dabigatran attenuates atherosclerosis in ApoE deficient mice. Arch Med Sci. 2014; 10(1):154-60. PMC: 3953984. DOI: 10.5114/aoms.2014.40742. View

Imiya M, Matsuo T . Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction. Thromb Res. 1997; 88(2):245-50. DOI: 10.1016/s0049-3848(97)00235-1. View

Muhlestein J . Effect of antiplatelet therapy on inflammatory markers in atherothrombotic patients. Thromb Haemost. 2010; 103(1):71-82. DOI: 10.1160/TH09-03-0177. View

Adams Jr H, Woolson R, Biller J, Clarke W . Studies of Org 10172 in patients with acute ischemic stroke. TOAST Study Group. Haemostasis. 1992; 22(2):99-103. DOI: 10.1159/000216301. View

Hosomi N, Naya T, Kohno M, Kobayashi S, Koziol J . Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke. J Neurol. 2007; 254(5):605-12. DOI: 10.1007/s00415-006-0365-y. View

Giugliano R, Ruff C, Braunwald E, Murphy S, Wiviott S, Halperin J . Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369(22):2093-104. DOI: 10.1056/NEJMoa1310907. View

10.

Okada T, Nakase T, Sasaki M, Ishikawa T . Do the antithrombotic therapy at the time of intracerebral hemorrhage influence clinical outcome? analysis between the difference of antiplatelet and anticoagulant agents and clinical course. J Stroke Cerebrovasc Dis. 2014; 23(7):1781-8. DOI: 10.1016/j.jstrokecerebrovasdis.2014.04.036. View

11.

Kawai H, Yuki S, Sugimoto J, TAMAO Y . Effects of a thrombin inhibitor, argatroban, on ischemic brain damage in the rat distal middle cerebral artery occlusion model. J Pharmacol Exp Ther. 1996; 278(2):780-5. View

12.

Lippi G, Favaloro E . Recent guidelines and recommendations for laboratory assessment of the direct oral anticoagulants (DOACs): is there consensus?. Clin Chem Lab Med. 2014; 53(2):185-97. DOI: 10.1515/cclm-2014-0767. View

13.

Feistritzer C, Lenta R, Riewald M . Protease-activated receptors-1 and -2 can mediate endothelial barrier protection: role in factor Xa signaling. J Thromb Haemost. 2005; 3(12):2798-805. DOI: 10.1111/j.1538-7836.2005.01610.x. View

14.

Kobayashi S, Tazaki Y . Effect of the thrombin inhibitor argatroban in acute cerebral thrombosis. Semin Thromb Hemost. 1997; 23(6):531-4. DOI: 10.1055/s-2007-996131. View

15.

Antonino M, Mahla E, Bliden K, Tantry U, Gurbel P . Effect of long-term clopidogrel treatment on platelet function and inflammation in patients undergoing coronary arterial stenting. Am J Cardiol. 2009; 103(11):1546-50. DOI: 10.1016/j.amjcard.2009.01.367. View

16.

Xu W, Andersen H, Whitmore T, Presnell S, Yee D, Ching A . Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci U S A. 1998; 95(12):6642-6. PMC: 22580. DOI: 10.1073/pnas.95.12.6642. View

17.

Connolly S, Ezekowitz M, Yusuf S, Eikelboom J, Oldgren J, Parekh A . Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361(12):1139-51. DOI: 10.1056/NEJMoa0905561. View

18.

Fornai F, Carrizzo A, Forte M, Ambrosio M, Damato A, Ferrucci M . The inflammatory protein Pentraxin 3 in cardiovascular disease. Immun Ageing. 2016; 13(1):25. PMC: 4995820. DOI: 10.1186/s12979-016-0080-1. View

19.

Borissoff J, Otten J, Heeneman S, Leenders P, Van Oerle R, Soehnlein O . Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner. PLoS One. 2013; 8(2):e55784. PMC: 3567111. DOI: 10.1371/journal.pone.0055784. View

20.

Connolly T, Condra C, Feng D, COOK J, Stranieri M, Reilly C . Species variability in platelet and other cellular responsiveness to thrombin receptor-derived peptides. Thromb Haemost. 1994; 72(4):627-33. View