Elsevier

Thrombosis Research

Volume 129, Issue 3, March 2012, Pages 235-240
Thrombosis Research

Review
Thrombosis and Acute coronary syndrome

https://doi.org/10.1016/j.thromres.2011.12.026Get rights and content

Abstract

Acute coronary syndromes (ACS) represent the main clinical manifestation of atherosclerotic progression in the coronary district. Thrombosis plays a critical role in the patho-anatomical of ACS, as disruption of an atherosclerotic plaque exposes flowing blood to subendothelial collagen, tissue factor, and other procoagulant molecules that trigger activation of platelets and formation of fibrin within the vessel lumen.

Endothelial damage/dysfunction, inflammation and coagulation are closely related to the pathophysiology of ACS and may be inter-related.

Platelets play key roles in both the formation of the atheromatous plaque and clinical presentation of acute atherothrombotic events following plaque rupture. In the pathogenesis of the ACS, blood clotting activation has a crucial role and thrombin generation and TF may represent useful markers for the identification of patients at high risk of vascular events. Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents the crossroads between lipid metabolism and inflammatory response.

Introduction

ACS represent the culminating clinical manifestation of atherosclerotic progression in the coronary district. Thrombosis plays a critical role in the pathogenesis of ACS, as disruption of an atherosclerotic plaque exposes flowing blood to subendothelial collagen, tissue factor, and other procoagulant molecules that trigger activation of platelets and formation of fibrin within the vessel lumen. Anatomical substrate of ACS lesions is the unstable or vulnerable atherosclerotic plaque, whose sudden erosion or rupture can activate the hemostatic system.

Recent data have elucidated the contribution of traditional risk factors to increase the prothrombotic potential, also providing the evidence of association between environmental factors, hemostatic alterations, inflammation and vascular events. A large number of studies have also showed an association between hemostatic alterations and vascular events, underlying that endothelial dysfunction, platelets and the coagulation system are important determinants of both atherogenesis and atherothrombosis. In this scenario, oxidative stress, by changing the structure and function of lipoprotein particles, induces inflammatory cell activation and promotes apoptosis.

Hemostasis is a complex network of cellular and humoral systems that regulates the adequacy of blood flow through peripheral vascular districts. Platelet system, coagulative process, anticoagulant and fibrinolytic pathways, inflammation and endothelial dysfunction, are the main actors of this equilibrium between antithrombotic and prothrombotic factors.

Section snippets

Role of endothelial dysfunction in ACS

Endothelial damage/dysfunction, inflammation and coagulation are closely related to the pathophysiology of acute coronary syndromes (ACS) and may be inter-related.

Endothelial dysfunction represents the early step of atherothrombotic process. It is mainly characterized by the switch from a normal endothelial - vasodilatative, anticoagulant, inhibiting platelet function and pro-fibrinolytic – phenotype towards an abnormal– vasocostrictive, procoagulant, activating platelet and anti-fibrinolitic

Role of platelet hyper-reactivity in ACS

Several studies showed a role for platelets on progression of atherogenesis, both exerting a set of proatherogenic activities and becoming the link between endothelial function, hemostasis, immunity, and inflammatory pathways.

Platelets play key roles in both the formation of the atheromatous plaque and clinical presentation of acute atherothrombotic events following plaque rupture.

The first step in thrombus formation involves platelet adhesion, activation and aggregation. The trigger of

Role of blood clotting activation in ACS

Numerous studies have shown the main role of tissue factor (TF) in triggering the acute thrombotic events within atherothrombotic lesions. TF expression, mainly by endothelial cells and macrophages, increases in conditions of inflammation or injury, occurring during plaque destabilization and rupture, and likely results from interactions with T lymphocytes via the CD40-CD40 ligand signaling system. TF interacts with factor VIIa, forming an activating complex which binds and actives factor X and

Role of Fibrinolytic factors in ACS

Fibrinolytic system is activated concurrently with fibrin formation. Plasminogen is the inactive form of plasmin; it is produced in liver and has a great affinity for fibrin, being incorporated to the clot when it is formed. When converted into serine protease plasmin, by tissue plasminogen activator (t-PA) and urokinase, cuts C-terminal to these lysine and arginine residues and degrades fibrin promoting proteolytic clearance of the established thrombus.

Tissue plasminogen activator (t-PA) and

Blood clotting activation , thrombosis and inflammation

Different mechanisms have been demonstrated in the development of the atherosclerotic plaque and in the thrombotic transformation of the plaque. In the atherosclerotic plaque lipids are present, but there are also cytokines, adhesion molecules, chemokines, collagens, and enzymes secreted from multiple cell types. The primary adhesion of platelets on a compromised vascular endothelial surface occurs through the binding of platelet glycoprotein Ibα receptors to von Willebrand factor, whereas firm

Conclusions

Acute coronary syndromes (ACS) are still associated with high mortality and morbility and represent the most common cause of death in industrialized countries. Despite the advances in modern therapy, the rates of death and recurrences of patients with ACS remain high.

ACS is the result of interactions between cellulars and humoral mechanisms involved in local thrombus formation. Well-known risk factors are able to affect circulating and local procoagulant factors, so influencing the progression

Conflict of Interest

None.

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