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New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism.

Mekaj YH, Daci FT, Mekaj AY - Ther Clin Risk Manag (2015)

Bottom Line: The antithrombotic action of aspirin has long been recognized.Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs.Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo ; Department of Hemostasis and Thrombosis, National Blood Transfusion Center of Kosovo, University of Prishtina, Prishtina, Kosovo.

ABSTRACT
The antithrombotic action of aspirin has long been recognized. Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX) activity. Until recently, aspirin has been mainly used for primary and secondary prevention of arterial antithrombotic events. The aim of this study was to review the literature with regard to the various mechanisms of the newly discovered effects of aspirin in the prevention of the initiation and development of venous thrombosis. For this purpose, we used relevant data from the latest numerous scientific studies, including review articles, original research articles, double-blinded randomized controlled trials, a prospective combined analysis, a meta-analysis of randomized trials, evidence-based clinical practice guidelines, and multicenter studies. Aspirin is used in the prevention of venous thromboembolism (VTE), especially the prevention of recurrent VTE in patients with unprovoked VTE who were treated with vitamin K antagonists (VKAs) or with non-vitamin K antagonist oral anticoagulants (NOACs). Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs. Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries. Aspirin is indicated for the primary and secondary prevention as well as the treatment of cardiovascular diseases, including acute coronary syndrome, myocardial infarction, peripheral artery disease, acute ischemic stroke, and transient ischemic attack (especially in atrial fibrillation or mechanical heart valves). Aspirin can prevent or treat recurrent unprovoked VTEs as well as VTEs occurring after various surgeries or in patients with malignant disease. Recent trials have suggested that the long-term use of low-dose aspirin is effective not only in the prevention and treatment of arterial thrombosis but also in the prevention and treatment of VTE. Compared with VKAs and NOACs, aspirin has a reduced risk of bleeding.

No MeSH data available.


Related in: MedlinePlus

Mechanisms of antithrombotic effects of aspirin.Abbreviations: PGH2, prostaglandin H2; TXA2, thromboxane A2; COX-1, cyclooxygenase-1; TF, tissue factor; TFPI, tissue factor pathway inhibitor.
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f1-tcrm-11-1449: Mechanisms of antithrombotic effects of aspirin.Abbreviations: PGH2, prostaglandin H2; TXA2, thromboxane A2; COX-1, cyclooxygenase-1; TF, tissue factor; TFPI, tissue factor pathway inhibitor.

Mentions: Recent studies have explained the role and mechanisms of action of aspirin in the prevention of VTE. Aspirin-mediated prevention involves the inhibition of platelets. The binding of platelets and recruitment of neutrophils to the vascular endothelium is an early step in the development of deep vein thrombosis.27 Because the recruitment and rolling of leukocytes, as well as their initial attachment to vascular endothelium, is dependent on a glycoprotein called P-selectin, the inhibition of P-selectin is associated with a reduced weight of mice subjected to thrombus induced by ligation of the inferior vena cava.28 Additionally, platelet inactivation by aspirin results in the inhibition of the release of the following platelet-associated substances into the venous circulation: platelet factors V and XIII, fibrinogen, platelet factors 3 and 4, thrombospondin, von Willebrand factor (vWF), calcium ions, serotonin, and other substances that favor the development of venous thrombosis. Enzymatic complexes (especially prothrombinase complex) form on the surfaces of activated platelets, and a large number of receptors are available for these complexes.13 Aspirin also prevents thrombin formation that is catalyzed by the calcium ion-dependent complex of tissue factor (TF) and activated factor VII (FVIIa). The inhibition of this complex by aspirin promotes the inhibition of factors IX and X. The formation of the prothrombinase complex and thrombin is subsequently inhibited.29 Thrombin is the serine protease that converts fibrinogen to fibrin, which polymerizes to form a thrombus. The inhibition of thrombin production by aspirin can be explained by two additional mechanisms, as follows: increased secretion of TF pathway inhibitor (TFPI) as well as the acetylation of prothrombin and several membrane components.30 Some authors have proposed that aspirin impacts the quality of fibrin within the thrombus. Properties of fibrin are dependent on the structural characteristics at the molecular level and at the level of individual fibers. The properties also depend on the arrangements of the three-dimensional networks.31 Acetylation of fibrinogen is an important mechanism of action of aspirin. Acetylation increases the porosity of the fibrin network and therefore increases the rate of fibrinolysis.32 The antithrombotic effect of high doses of aspirin potentially stems from reduced synthesis of coagulation factors in the liver, and this mechanism resembles those of VKAs. Furthermore, a reduction in thrombin levels reduces FXIII activation.33,34 The overall mechanisms of aspirin in the prevention and treatment of arterial and VTE are presented in Figure 1.


New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism.

Mekaj YH, Daci FT, Mekaj AY - Ther Clin Risk Manag (2015)

Mechanisms of antithrombotic effects of aspirin.Abbreviations: PGH2, prostaglandin H2; TXA2, thromboxane A2; COX-1, cyclooxygenase-1; TF, tissue factor; TFPI, tissue factor pathway inhibitor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590672&req=5

f1-tcrm-11-1449: Mechanisms of antithrombotic effects of aspirin.Abbreviations: PGH2, prostaglandin H2; TXA2, thromboxane A2; COX-1, cyclooxygenase-1; TF, tissue factor; TFPI, tissue factor pathway inhibitor.
Mentions: Recent studies have explained the role and mechanisms of action of aspirin in the prevention of VTE. Aspirin-mediated prevention involves the inhibition of platelets. The binding of platelets and recruitment of neutrophils to the vascular endothelium is an early step in the development of deep vein thrombosis.27 Because the recruitment and rolling of leukocytes, as well as their initial attachment to vascular endothelium, is dependent on a glycoprotein called P-selectin, the inhibition of P-selectin is associated with a reduced weight of mice subjected to thrombus induced by ligation of the inferior vena cava.28 Additionally, platelet inactivation by aspirin results in the inhibition of the release of the following platelet-associated substances into the venous circulation: platelet factors V and XIII, fibrinogen, platelet factors 3 and 4, thrombospondin, von Willebrand factor (vWF), calcium ions, serotonin, and other substances that favor the development of venous thrombosis. Enzymatic complexes (especially prothrombinase complex) form on the surfaces of activated platelets, and a large number of receptors are available for these complexes.13 Aspirin also prevents thrombin formation that is catalyzed by the calcium ion-dependent complex of tissue factor (TF) and activated factor VII (FVIIa). The inhibition of this complex by aspirin promotes the inhibition of factors IX and X. The formation of the prothrombinase complex and thrombin is subsequently inhibited.29 Thrombin is the serine protease that converts fibrinogen to fibrin, which polymerizes to form a thrombus. The inhibition of thrombin production by aspirin can be explained by two additional mechanisms, as follows: increased secretion of TF pathway inhibitor (TFPI) as well as the acetylation of prothrombin and several membrane components.30 Some authors have proposed that aspirin impacts the quality of fibrin within the thrombus. Properties of fibrin are dependent on the structural characteristics at the molecular level and at the level of individual fibers. The properties also depend on the arrangements of the three-dimensional networks.31 Acetylation of fibrinogen is an important mechanism of action of aspirin. Acetylation increases the porosity of the fibrin network and therefore increases the rate of fibrinolysis.32 The antithrombotic effect of high doses of aspirin potentially stems from reduced synthesis of coagulation factors in the liver, and this mechanism resembles those of VKAs. Furthermore, a reduction in thrombin levels reduces FXIII activation.33,34 The overall mechanisms of aspirin in the prevention and treatment of arterial and VTE are presented in Figure 1.

Bottom Line: The antithrombotic action of aspirin has long been recognized.Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs.Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo ; Department of Hemostasis and Thrombosis, National Blood Transfusion Center of Kosovo, University of Prishtina, Prishtina, Kosovo.

ABSTRACT
The antithrombotic action of aspirin has long been recognized. Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX) activity. Until recently, aspirin has been mainly used for primary and secondary prevention of arterial antithrombotic events. The aim of this study was to review the literature with regard to the various mechanisms of the newly discovered effects of aspirin in the prevention of the initiation and development of venous thrombosis. For this purpose, we used relevant data from the latest numerous scientific studies, including review articles, original research articles, double-blinded randomized controlled trials, a prospective combined analysis, a meta-analysis of randomized trials, evidence-based clinical practice guidelines, and multicenter studies. Aspirin is used in the prevention of venous thromboembolism (VTE), especially the prevention of recurrent VTE in patients with unprovoked VTE who were treated with vitamin K antagonists (VKAs) or with non-vitamin K antagonist oral anticoagulants (NOACs). Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs. Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries. Aspirin is indicated for the primary and secondary prevention as well as the treatment of cardiovascular diseases, including acute coronary syndrome, myocardial infarction, peripheral artery disease, acute ischemic stroke, and transient ischemic attack (especially in atrial fibrillation or mechanical heart valves). Aspirin can prevent or treat recurrent unprovoked VTEs as well as VTEs occurring after various surgeries or in patients with malignant disease. Recent trials have suggested that the long-term use of low-dose aspirin is effective not only in the prevention and treatment of arterial thrombosis but also in the prevention and treatment of VTE. Compared with VKAs and NOACs, aspirin has a reduced risk of bleeding.

No MeSH data available.


Related in: MedlinePlus