Influence of PAR-1 in patients with non-valvular atrial fibrillation: The antiplatelet effect of dabigatran

Oi, Kiyotaka; Shimizu, Mie; Natori, Tatsunori; Tsuda, Kôichi; Yoshida, Makiko; Kamada, Asami; Ishigaku, Yoko; Narumi, Shinsuke; Oura, Kazumasa; Maeda, Tetsuya; Terayama, Yasuo

doi:10.1016/j.thromres.2021.02.019

Cited by 4 publications

(4 citation statements)

References 26 publications

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“…Finally, dabigatran blocks thrombin activation of protease-activated receptor-1 (PAR-1) to indirectly reduce platelet activation. In addition, dabigatran directly suppresses the expression of Pselectin (CD62P) in the membranes of platelets, which in turn limits platelet activation [16]. Therefore, dabigatran has the potential to be used as both an antithrombotic and antiplatelet drug.…”

Section: Mechanism Of Action Of Dabigatranmentioning

confidence: 99%

A review on increasing risk for gastrointestinal bleeding associated with dabigatran

2024

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Dabigatran, a reversible direct thrombin inhibitor, is widely used in clinical practice as a therapeutic option due to its unique mechanism of action in comparison to other anticoagulants. Although patients taking dabigatran experience a reduced risk of fatal bleeding, a higher risk of gastrointestinal bleeding (GIB) is associated with dabigatran, and its rational use between anticoagulation and bleeding is challenging for clinicians. To prevent GIB, it is imperative for clinicians to understand the pharmacological characteristics of dabigatran to ensure that its prescription should be avoided in patients with bleeding. In this review, we summarize the mechanism of action and pharmacokinetics of dabigatran and bleeding sites in the gastrointestinal tract in patients treated with dabigatran, as well as discuss the factors that increase the risk of dabigatran-induced GIB, including dose, age, drug interactions, race, genetics and past medical history. Finally, the treatment and prevention of GIB with dabigatran is also discussed. This review will help clinicians choose their drugs and doses more carefully for treating GIB.

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Section: Mechanism Of Action Of Dabigatranmentioning

confidence: 99%

A review on increasing risk for gastrointestinal bleeding associated with dabigatran

2024

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“…33 In a recently published study, dabigatran, through the inhibition of PAR-1, was shown to ameliorate tubulointerstitial fibrosis in unilateral ureteral obstruction-induced renal injury. 34 The antiplatelet effect of dabigatran has also been postulated based on the effect on PAR-1 receptors, 35 which in turn may increase the risk of bleeding and ARN. Interestingly, in an RCT performed by Correa et al, a PAR-1 inhibitor, vorapaxar, was shown to be safe for CKD patients.…”

Section: Pathogenesismentioning

confidence: 99%

Anticoagulant-related nephropathy: Focus on novel agents. A review

Zakrocka¹,

Załuska²

2022

Adv Clin Exp Med

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Anticoagulant-related nephropathy (ARN) is a novel and not well-studied cause of acute kidney injury (AKI). The prevalence of ARN varies significantly between studies and is estimated at 20% in patients treated with warfarin. Patients with ARN have a significantly higher mortality risk and an increased risk of chronic kidney disease (CKD). Unexplained AKI with hematuria are clinical manifestations of ARN. In most cases, ARN is diagnosed within the first 2 months of anticoagulant therapy, but later ARN occurrence is possible. Among the studied anticoagulants, most data concern warfarin toxicity, whereas cases of ARN caused by direct oral anticoagulants (DOACs) have also been presented. Tubular obstruction by red blood cell casts or hemoglobin and iron tubular toxicity are the postulated mechanisms of ARN. On the molecular level, the inhibition of thrombin and protease-activated receptor-1 (PAR-1), leading to endothelial susceptibility to damage or abnormal protein C endothelial signaling, is suggested to contribute to ARN. Older age, impaired kidney function, hypertension, and diabetes mellitus are the main risk factors for ARN, but their significance may differ between anticoagulants. From therapeutic options, the withdrawal of the anticoagulant and the administration of its antidote, as well as corticosteroids or N-acetylcysteine, are proposed. Since the number of patients with kidney diseases on anticoagulants increases, and DOACs are starting to be more useful in this group of patients, we aim to summarize the pathogenesis, clinical picture and possible ways of treatment of DOAC-induced ARN.

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“…Their efficacy in the setting of atherosclerotic diseases has been recently proven [ 164 ]. Dabigatran in particular may attenuate the process of platelet activation as shown in thrombin-stimulated platelets where dabigatran inhibited CD62 [ 165 ]. This platelet inhibitory effect appears to be dose-dependent [ 166 ].…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches

Theofilis

Sagris

Oikonomou

et al. 2022

IJMS

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Platelets are at the forefront of human health and disease following the advances in their research presented in past decades. Platelet activation, their most crucial function, although beneficial in the case of vascular injury, may represent the initial step for thrombotic complications characterizing various pathologic states, primarily atherosclerotic cardiovascular diseases. In this review, we initially summarize the structural and functional characteristics of platelets. Next, we focus on the process of platelet activation and its associated factors, indicating the potential molecular mechanisms involving inflammation, endothelial dysfunction, and miRs. Finally, an overview of the available antiplatelet agents is being portrayed, together with agents possessing off-set platelet-inhibitory actions, while an extensive presentation of drugs under investigation is being given.

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Influence of PAR-1 in patients with non-valvular atrial fibrillation: The antiplatelet effect of dabigatran

Cited by 4 publications

References 26 publications

A review on increasing risk for gastrointestinal bleeding associated with dabigatran

A review on increasing risk for gastrointestinal bleeding associated with dabigatran

Anticoagulant-related nephropathy: Focus on novel agents. A review

Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches

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