Venous and arterial thrombosis – pathogenesis and the rationale for anticoagulation

Abstract

SummaryThromboembolic disorders are major causes of morbidity and mortality. It is well-recognised that the pathogenesis is different for arterial and venous thrombosis; however, both involve coagulation activation. Anticoagulants are used for the prevention and treatment of a wide variety of thromboembolic and related conditions. Agents with anti-inflammatory properties in addition to anticoagulation may be particularly beneficial. Traditional anticoagulants, although effective, are associated with certain limitations. Understanding the pathological processes associated with thrombosis and the rational target for anticoagulation is essential, not only for the development of safer and more effective agents, but also for better clinical management of patients who require anticoagulation therapy. In recent years, new oral agents that target single enzymes of the coagulation cascade have been developed – some of those are in advanced stages of clinical development. Based on scientific rationale, both factor Xa and thrombin are viable targets for effective anticoagulation.

Elevated Prothrombin Promotes Venous, but Not Arterial, Thrombosis in Mice

“…Arterial thrombosis and venous thrombosis/thromboembolism are traditionally regarded as distinct diseases with respect to their epidemiology and treatment strategies (reviewed in 1,2 ). The presence of certain non-overlapping risk factors suggests that distinct features in the arterial and venous environments confer differential pathophysiology.…”

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

“…Acute coronary syndrome (ACS) is caused by thrombosis in the coronary arteries. Rupture of an atherosclerotic plaque triggers thrombogenesis by platelet activation and aggregation and activation of the coagulation cascade, leading to complete or partial vessel occlusion [1]. The current gold standard of care for short-term and long-term secondary prevention of cardiovascular events in patients with ACS is dual antiplatelet therapy with acetylsalicylic acid (ASA) and a thienopyridine such as clopidogrel [2,3].…”

“…Arterial thrombosis involves both platelet aggregation and the activation of the coagulation cascade, providing the rationale for anticoagulant therapy in addition to antiplatelet therapy for secondary prevention of cardiovascular events in patients with ACS [1]. A number of studies have assessed the risks and benefits of warfarin therapy in addition to ASA [6,7] or dual antiplatelet therapy (ASA and clopidogrel) [8] for the prevention of cardiovascular events in patients with ACS.…”

Screening of Clotting System Disorders by Laboratory Tests

“…Артериальные тромбы образуются обычно в области поврежденных атеро-склеротических бляшек и состоят преимущественно из агрегатов тромбоцитов, скрепленных нитями фибрина. Венозные тромбы могут образовываться в участках без видимых повреждений стенки сосуда, но с замедленной скоростью тока крови и состоят преимущественно из фибрина, эритроцитов и неболь-шого количества тромбоцитов [10]. Несмотря на раз-личия в составе и структуре венозных и артериальных тромбов их формирование и стабилизация в значи-тельной степени зависит от образования тромбина.…”