To clot, or not to clot – Antithrombotic therapy is the question

E Osuch,A Marais

doi:10.4102/safp.v61i3.4966

Abstract

Haemostasis and thrombosis rely on three components namely the vascular endothelial wall, blood platelets and the coagulation cascade. Non-physiologic excessive thrombosis occurs when haemostatic processes are dysfunctional, causing undue clot formation or reduced clot lysis. Antithrombotic agents including antiplatelet, anticoagulation and fibrinolytic agents are essential for the prophylaxis and pharmacological management of venous thromboembolism and arterial thrombosis. Anticoagulation treatment options have expanded steadily over the past few decades, providing a greater number of agents. Anticoagulants that directly target the enzymatic activity of thrombin and factor Xa have recently been developed to address the inadequacies of traditional vitamin K antagonists. Appropriate use of these agents requires knowledge of their individual characteristics, risks, and benefits.

Highlights

Haemostasis, the process of thrombin-stimulated fibrin clot formation at the site of vessel injury, involves several processes
Thrombin activates platelets via G-protein coupled protease-activated receptors (PARs) while adenosine diphosphate (ADP) binds to two G-protein coupled receptors.[3]
In order to restore vessel patency following haemostasis, the clot must be removed by the proteolytic enzyme, plasmin, which is converted from plasminogen, in the presence of tissue plasminogen activator

Summary

Introduction

Haemostasis, the process of thrombin-stimulated fibrin clot formation at the site of vessel injury, involves several processes. The main physiologic platelet stimuli include adenosine diphosphate (ADP), thrombin and collagen.[2] Intimal injury impairs the production of nitric oxide and prostacyclin and exposes subendothelial collagen. This results in platelet adherence, platelet activation, and secretion of platelets granules. Thrombin is active in both circulating and clot-bound forms.[5] Components of the intrinsic pathway (i.e., factors VIII, IX, XI) are responsible for amplification of this process.[6] In order to restore vessel patency following haemostasis, the clot must be removed by the proteolytic enzyme, plasmin, which is converted from plasminogen, in the presence of tissue plasminogen activator (tPA). Plasmin activity is regulated by vascular endothelial cells that secrete both protease plasminogen activators, and plasminogen activator inhibitors.[7]

Antiplatelet drugs

ADP receptor antagonists

Fibrinolytic drugs

Anticoagulant drugs

Unfractionated heparins

Conclusion