Fibrinolytic system

This article has been translated from WikiSkripta; ready for the editor's review.

Fibrinolytics, also thrombolytics, are drugs used to dissolve already formed thrombi. They work by activating the fibrinolytic system', which is the functional opposite of the coagulation system.

Fibrinolytic System

First, the proenzyme ``plasminogen (present in the clot and in plasma) is converted to ``plasmin. The plasminogen activators'' (tissue plasminogen activator t-PA and urokinase-type plasminogen activator u-PA) are responsible for this, whose functional antagonist is plasminogen activator inhibitor 1 (PAI-1). Plasmin acts as a protease that cleaves fibrin into degradation products (but it acts with little substrate specificity and can also cleave fibrinogen). So fibrinolytics work as plasminogen activators.

Fibrinolysis diagram

Under normal circumstances, fibrinolysis is limited to thrombus, free plasmin is rapidly neutralized by α₂-antiplasmin. If the fibrinolytic system were to be systemically activated, imbalance and bleeding would occur. The success of fibrinolysis depends on the age of the thrombus - the older it is, the more difficult it is to lyse.

 For more information see Fibrinolysis.

Ideal Fibrinolytic

• It is administered intravenously.
• It acts selectively on the thrombus.
• Does not activate plasminogen to plasmin in plasma.

Indication

Thrombolytics are used to dissolve an already formed clot (venous and arterial) - in 'acute conditions:

• extensive pulmonary embolism,
• thrombosis of large venous systems,
• arterial occlusion, embolism in the systemic circulation,
• Worldwide, thrombolysis is also used in acute heart attacks, but coronary angiography with angioplasty is mainly used in the Czech Republic.

Contraindications

• Bleeding condition or risk of bleeding
• Recent surgery, puncture of the artery or trauma
• Ulcer disease
• Recent stroke / TIA (<2 months; not but acute)
• Cancer.

Side effects

• Bleeding

Medicines used

Basic groups of fibrinolytics

first generation fibrinolytics	streptokinase, urokinase	non-selective, induces systemic fibrinolysis
fibrinolytics II. generation	t-PA, anistreplase, alteplase	selective binding to fibrin, not systemic fibrinolysis
fibrinolytics III. generation	reteplase, tenecteplase	selective binding to fibrin, no systemic fibrinolysis, faster onset than II. generation

Streptokinase

 For more information see Streptokinase.

is a non-enzymatic protein from β-hemolytic streptococci, acting as an indirect activator of plasminogen (forms a complex with plasminogen converting free plasminogen to plasmin). The plasma half-life is 20 minutes. It is very effective, cheap, but it is antigenic and has a hypotensive effect. Adverse effects may include bleeding, allergy, fever, or even anaphylactic shock.

Urokinase

 For more information see Urokinase.

is a human protease synthesized in the kidneys, it directly activates plasminogen. Due to its origin in the kidneys, it is not antigenic, but it is less effective.

Tissue plasminogen activator (t-PA)

it acts selectively on thrombus but has a shorter half-life than streptokinase (5–10 min), which is associated with a higher incidence of reocclusion. It is highly effective. It is used as recombinant rt-PA or alteplase'.

Anistreplase (ASPAC – acetylated streptokinase-plasminogen activator complex)

it has a long half-life (90 min), so it is administered as a bolus intravenously. Acts more selectively on fibrin than on fibrinogen, unbound anistreplase is inactivated in plasma by α₂-antiplasmin. It is antigenic. It is mainly used in acute myocardial infarction.

Links

Related Articles

• Hemocoagulation
• Hemocoagulation versus anticoagulation
• Anticoagulants

Source

• LINCOVÁ, Dagmar – FARGHALI, Hassan, et al. Basic and applied pharmacology. 2. edition. Prague : Galen, 2007. pp. 277–279. ISBN 978-80-7262-373-0.

External Resources

• SOME ASPECTS OF ACUTE PULMONARY EMBOLISM TREATMENT prof. MD Jiří Widimský, DrSc., FESC, Internal medicine for practice 2001/10

• Recommended procedures of the European Society of Cardiology for the diagnosis and treatment of acute pulmonary embolism, version 2014. Summary document prepared by the Czech Society of Cardiology (2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Summary document prepared by the Czech Society of Cardiology) Richard Rokyta, Martin Hutyrab, Pavel Jansac