Thrombolysis is the breakdown (lysis) by pharmacological means, of blood clots. It is colloquially referred to as clot busting for this reason. It works by stimulating fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator, the protein that normally activates plasmin.

Agents

Thrombolysis requires the use of thrombolytic drugs, which are either derived from Streptomyces spp. or (more recently) the effect of recombinant technology, where human activators of plasminogen (e.g. tissue plasminogen activator, tPA) are manufactured by bacteria.

Some commonly used thrombolytics are

• streptokinase
• urokinase
• alteplase (recombinant tissue plasminogen activator or rtPA).

Aminocaproic acid and tranexamic acid are used as inhibitors of fibrinolysis, which act by blocking the lysine binding site on plasminogen. They are used in menorrhagia and bleeding tendency, but are not very effective in antagonising the thrombolytic drugs in case of overdose or sudden severe bleeding.

Principles

Formation of blood clots lies at the basis of a number of serious diseases (see below). By breaking down the clot, the disease process can be arrested, or the complications reduced. While other anticoagulants (such as heparin) decrease the "growth" of a clot, thrombolytic agents actively reduce the size of the clot.

All thrombolytic agents work by activating the enzyme plasminogen, which clears the cross-linked fibrin mesh (the backbone of a clot). This makes the clot soluble and subject to further proteolysis by other enzymes, and restores blood flow over occluded blood vessels.

Uses

Diseases where thrombolysis is used:

• Myocardial infarction
• Cerebrovascular accident
• Massive pulmonary embolism

Contraindications

These are contraindicated in bleeding disorders, active bleeding and when there has been recent surgery. Diabetic retinopathy is a relative contraindication.