Fibrinolysis is the physiological process of dissolving a blood clot that is part of homeostasis and is triggered by the activation of a number of enzymes. This process plays a role in maintaining the patency of blood vessels and in angiogenesis, wound healing, tumor growth and metastasis formation.
Fibrinolysisis a physiological process that opposes clotting. Why? Because it dissolves the clot.
Fibrinolysis - course
The fibrinolytic enzyme plasmin circulates in the plasma. Plasmin breaks down fibrin, fibrinogen, plasma factors: V, VIII and XII and prothrombin. Plasmin is produced from inactive proenzyme - plasminogen under the influence of tissue plasminogen activator (t-PA) and plasminogen activator of urokinase type (u-PA). The transformation of plasminogen into plasmin can also occur under the influence of thrombin.
Tissue plasminogen activator and urokinase plasminogen activator are produced in the endothelium (t-PA) and various cells and organs, including the kidney (u-PA). They are formed in the form of single-chain precursors, which are transformed into active two-chain forms by kallikrein or plasmin. Factor XII breakdown products in plasma activate the production of kinins that dilate blood vessels.
T-PA is primarily important in dissolving fibrin, and thus maintaining the patency of blood vessels. On the other hand, plasmin, which is formed with the participation of u-PA, causes the activation of the so-called metalloproteinases (a group of proteolytic enzymes) that play a role in tissue remodeling and cell migration (leading to angiogenesis, helping in wound healing, tumor growth and metastasis formation).
Anti-fibrinolysis mechanism
There are 2 inhibitors of plasminogen activators: PAI-1 and PAI-2 - these are proteins produced in megakaryocytes, liver and endothelial cells (PAI-1), as well as in placenta, monocytes (PAI-2). They differ in a slightly different mechanism of action. Plasmin is an inhibitor of plasma, a substance produced in the liver, alpha2-antiplasmin. If plasma alpha2-antiplasmin is depleted, plasmin is neutralized by alpha2-macroglobulin.
Another fibrinolysis inhibitor, procarboxypeptidase B2, is activated by thrombin (TAFI)
In the process of decayof fibrin and fibrinogen by plasmin, degradation products are formed - fragments X, Y, D, E. During plasmin digestion of cross-linked fibrin, instead of fragment D, Dimer D is formed - an important diagnostic marker that plays a role in the diagnostic process of venous thromboembolism. The limit value depends on the laboratory. The most commonly reported value of 500ng / ml is the limit below which VTE is unlikely.
Disorders of fibrinolysis
Disturbances of fibrinolysis may occur with the intensification or weakening of this process.
Congenital hemorrhagic diathesis is a group of diseases involving, among others, on increased activity of fibrinolysis. After the vessel wall is damaged, bleeding is difficult to control, because the clot dissolves very quickly. Fibrinolysis inhibitors are used to relieve symptoms.
The process of fibrinolysis is disturbed, also in the syndrome of disseminated intravascular coagulation (DIC). It is a syndrome secondary to many clinical conditions such as :
- sepsa
- extensive trauma
- acute pancreatitis
- malignant neoplasms
consisting in the generalized activation of the blood clotting process, and the activation or inhibition of the fibrinolysis process. Multiple blood clots in the microcirculation develop, resulting in ischemia of many organs. The consumption of platelets, fibrinogen, plasma coagulation factors is manifested by hemorrhagic diathesis.
In certain disease states, such as:
- ischemic stroke
- myocardial infarction
- pulmonary embolism
the substrate is the closure of the lumen of a blood vessel by a thrombus.
The basis of life-saving therapy in some cases is thrombus dissolution using fibrinolytic agents. Fibrinolytic drugs include urokinase, alteplase, and streptokinase. These drugs are administered intravenously by infusion.
The time from the onset of symptoms, diagnosis to administration of drugs in most cases has a decisive value on a person's life.