#Fibrinolysis

#Biology

#Advanced

Introduction

• Fibrinolysis is a process that removes clots following hemostasis and clot retraction, preventing uncontrolled thrombosis and embolism.

• Fibrinolysis is the breakdown of a fibrin clot.

• Many drugs have fibrinolytic properties that can be used to treat uncontrolled clotting and embolism, including streptokinase, synthetic t-PA, aspirin, heparin, warfarin, and citrates.

• Patients suspected to be having a blood clot-induced stroke should be screened for hemorrhage and aneurysm first, since fibrinolytic treatment would help with a stroke but make bleeding conditions much more dangerous.

• There are two types of fibrinolysis: primary fibrinolysis and secondary fibrinolysis. Primary fibrinolysis is a normal body process, whereas secondary fibrinolysis is the breakdown of clots due to a medication, medical disorder, or other cause.

Mechanisms of Primary Fibrinolysis

• Primary fibrinolysis normally occurs following clot retraction, in which the clot has already condensed considerably in size.

• The main enzyme in primary fibrinolysis is plasmin, a proteolytic enzyme that degrades fibrin mesh. Plasmin cleaves fibrin at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidneys and liver.

• Plasmin is produced in an inactive form, plasminogen, in the liver. Plasminogen cannot cleave fibrin and circulates in the bloodstream.

• Instead, it is incorporated into the clot when it is formed and then activated into plasmin later. Plasminogen is activated to plasmin by tissue plasminogen activator (t-PA) and urokinase, an enzyme found in the urine.

  
  

Fibrinolysis : Blue arrows denote stimulation and red arrows inhibition.

• T-PA is released into the blood very slowly by the damaged endothelium of the blood vessels. T-PA and urokinase are themselves inhibited by plasminogen activator inhibitor-1 and plasminogen activator inhibitor-2 (PAI-1 and PAI-2).

• In contrast, plasmin further stimulates plasmin generation by producing more active forms of both tissue plasminogen activator (tPA) and urokinase. Following fibrin degradation by plasmin, old activated platelets from the platelet plug are phagocytized and destroyed by macrophages.

• Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin -activatable fibrinolysis inhibitor (TAFI), which modifies fibrin to make it more resistant to the tPA-med