Targeting factor Xa and thrombin: impact on coagulation and beyond

Abstract

SummaryGreat advances have been made in recent years in understanding the haemostatic system and the molecular and cellular basis of thrombus formation. Although directly targeting factor Xa or thrombin (factor IIa) for effective anticoagulation is now well established, evidence has emerged suggesting that factor Xa and thrombin are involved in other physiological and pathophysiological cellular processes, including inflammation. These non-haemostatic activities of factor Xa and thrombin are predominantly mediated via the activation of proteinaseactivated receptors. Studies have indicated a potential role of coagulation proteins (including factor Xa and thrombin) in the progression of disease conditions such as atherothrombosis. Preclinical studies have provided evidence for the effects of direct factor Xa or direct thrombin inhibition beyond anticoagulation, including anti-inflammatory activities and atherosclerotic plaque stabilisation. In this article, the non-haemostatic activities of factor Xa and thrombin and the effects of direct inhibition of these coagulation factors on these activities are summarised. In addition, the potential roles of factor Xa and thrombin in atherosclerosis and atherothrombosis are explored and the cardiovascular profiles of rivaroxaban, apixaban and dabigatran etexilate observed in phase III clinical studies are discussed.

Features of Modern Anticoagulant Therapy in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease

“…ППОАК имеют принципиально отличный от варфарина механизм действия. Их мишенями являются тромбин (для да-бигатрана) и Xа фактор (для ривароксабана, апикса-бана и эдоксабана), которые, как было показано, по-мимо каскада свертывания активно участвуют и в других процессах (в воспалительных, пролифератив-ных, ремоделирования тканей, регуляции эндотели-альной функции) [33]. В свою очередь, хроническое воспаление и дисфункция эндотелия лежат в основе многих патологических процессов, в том числе ХБП и атеросклероза.…”

Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation

“…On the contrary, direct thrombin inhibitors (e.g., dabigatran) bind to active catalytic site of thrombin (factor IIa, serine protease) in competitive and reversible manner and block the final stage of coagulation cascade, that is, synthesis of fibrin from fibrinogen and its stabilization (Figure 1) [20][21][22]. Dabigatran is capable of inhibiting both free thrombin and fibrin-bound thrombin.…”

“…Dabigatran is capable of inhibiting both free thrombin and fibrin-bound thrombin. Because thrombin realizes multiple effects in hemostatic system, for example, activation of coagulation factors V, VIII, XI and XIII; inhibition of fibrinolysis; platelet activation; inflammatory changes and so on, dabigatran interferes with these reactions as well [20][21][22].…”

Patients with atrial fibrillation undergoing percutaneous coronary intervention. Current concepts and concerns: part II

“…Novel oral anticoagulants in patient with atrial fibrillation undergoing percutaneous coronary intervention The use of NOACs 15 is one of the major concerns in patients with AF undergoing PCI because of their increasing utilization in AF patients for stroke prevention, [16][17][18] while much less evidence has become available to guide their use in a clinical scenario of AF patients who present with ACS or undergo elective PCI. Current guidelines consist mainly of expert opinions based on observational data.…”

“…Since they do not require regular laboratory monitoring and have fewer food and drug interactions and a stable anticoagulant effect with fixed dose, they were favored for stroke prevention in AF. [16][17][18] However, there are few data to support the use of the NOACs as part of triple antithrombotic therapy or in conjunction with single antiplatelet therapy instead of warfarin in patients after PCI, since patients with ACS, MI, or receiving dual antiplatelet therapy were excluded from the AF trials, and patients with AF and indications for anticoagulation were excluded from the ACS trials.…”