Фибринолиз

Фибринолиз - это процесс , который предотвращает сгустков крови . выращивание и проблематичных Первичный фибринолиз - это нормальный процесс тела, в то время как вторичный фибринолиз - это расщепление сгустков из -за лекарства, медицинского расстройства или какой -либо другой причины.

В фибринолизе фибриновый сгусток, продукт коагуляции , разрушается. Его основной фермент плазмин сокращает фибриновую сетку в различных местах, что приводит к производству циркулирующих фрагментов, которые очищаются другими протеазами или почками и печенью .

Физиология

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Плазмин продуцируется в неактивной форме, плазминоген , в печени. Хотя плазминоген не может расщеплять фибрин, он по -прежнему имеет сродство к нему и включается в сгусток при его образовании.

Активатор тканевого плазминогена (T-PA) и урокиназа являются агентами, которые преобразуют плазминоген в активное плазмин, что позволяет возникать фибринолиз. T-PA высвобождается в кровь медленно благодаря поврежденному эндотелию кровеносных сосудов, так что через несколько дней (когда кровотечение остановилось) сгустка разбивается. Это происходит потому, что плазминоген попал в сгусток, когда он образовался; Поскольку он медленно активируется, он разрушает фибриновую сетку. T-PA и урокиназа сами ингибируются ингибитором активатора плазминогена-1 и ингибитором активатора плазминогена (PAI-1 и PAI-2). Напротив, плазминоген дополнительно стимулирует генерацию плазмина, продуцируя более активные формы как активатора тканевого плазминогена (TPA), так и урокиназы.

α₂-Antiplasmin and α₂-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-mediated plasminogen.

Measurement

Plasmin breaks down fibrin into soluble parts called fibrin degradation products (FDPs). FDPs compete with thrombin, and thus slow down clot formation by preventing the conversion of fibrinogen to fibrin. This effect can be seen in the thrombin clotting time (TCT) test, which is prolonged in a person that has active fibrinolysis.

FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and confirms that fibrinolysis has occurred. It is therefore used to indicate deep-vein thrombosis, pulmonary embolism, DIC and efficacy of treatment in acute myocardial infarction. Alternatively, a more rapid detection of fibrinolytic activity, especially hyperfibrinolysis, is possible with thromboelastometry (TEM) in whole blood, even in patients on heparin. In this assay, increased fibrinolysis is assessed by comparing the TEM profile in the absence or presence of the fibrinolysis inhibitor aprotinin. Clinically, the TEM is useful for near real-time measurement of activated fibrinolysis for at-risk patients, such as those experiencing significant blood loss during surgery.

Testing of overall fibrinolysis can be measured by a euglobulin lysis time (ELT) assay. The ELT measures fibrinolysis by clotting the euglobulin fraction (primarily the fibrinolytic factors fibrinogen, PAI-1, tPA, α₂-antiplasmin, and plasminogen) from plasma and then observing the time required for clot dissolution. A shortened lysis time indicates a hyperfibrinolytic state and bleeding risk. Such results can be seen in peoples with liver disease, PAI-1 deficiency or α₂-antiplasmin deficiency. Similar results are also seen after administration of DDAVP or after severe stress.

Role in disease

Few congenital disorders of the fibrinolytic system have been documented. Nevertheless, excess levels of PAI and α₂-antiplasmin have been implicated in metabolic syndrome and various other disease states.

However, acquired disturbance of fibrinolysis (hyperfibrinolysis), is not uncommon. Many trauma patients have an overwhelming activation of tissue factor and thus massive hyperfibrinolysis. Hyperfibrinolysis may occur in other disease states. It could lead to massive bleeding if not diagnosed and treated early enough.

The fibrinolytic system is closely linked to control of inflammation, and plays a role in disease states associated with inflammation. Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products have some vascular permeability inducing effects.

Pharmacology

In a process called thrombolysis (the breakdown of a thrombus), fibrinolytic drugs are used. They are given following a heart attack to dissolve the thrombus blocking the coronary artery; experimentally after a stroke to allow blood flow back to the affected part of the brain; and in the event of pulmonary embolism.

Thrombolysis refers to the dissolution of the thrombus due to various agents while fibrinolysis refers specifically to the agents causing fibrin breakdown in the clot.

Antifibrinolytics, such as aminocaproic acid (ε-aminocaproic acid) and tranexamic acid are used as inhibitors of fibrinolysis. Their application may be beneficial in patients with hyperfibrinolysis because they arrest bleeding rapidly if the other components of the haemostatic system are not severely affected. This may help to avoid the use of blood products such as fresh frozen plasma with its associated risks of infections or anaphylactic reactions.

Fibrinolytic enzymes

• Anistreplase
• Desmoteplase
• Streptokinase
• Nattokinase
• Lumbrokinase
• Serrapeptase
• Papain
• DNase
• Bromelain
• Honokiol

Внешние ссылки

• Графическое представление фибринолитического пути (сайт недоступен)