Thrombolysis

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Thrombolysis is the breakdown (lysis) of blood clots^[1] by pharmacological means. 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.

Contents 1 Agents 2 Principles 3 Uses 4 Contraindications 5 References

[edit] 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).
• reteplase
• tenecteplase

[edit] 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.

[edit] Uses

Diseases where thrombolysis is used:

• Myocardial infarction
• Stroke (ischemic stroke)^[2]
• Massive pulmonary embolism
• Acute limb ischaemia

Apart from streptokinase, all thrombolytic drugs are administered together with heparin (unfractionated or low molecular weight heparin), usually for 24-48 hours.

Thrombolysis is usually intravenous. It may also be used during an angiogram (intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours.

In some settings, emergency medical technicians may administer thrombolysis for heart attacks in prehospital settings. (Although in the UK it is more common for a Paramedic to administer thrombolysis - rather than technicians)

[edit] Contraindications

These are contraindicated in bleeding disorders, active bleeding and when there has been recent surgery. Diabetic retinopathy is a relative contraindication, as is untreated high blood pressure. Warfarin treatment increases risk of bleeding and is a relative contraindication.

Streptokinase is contraindicated in patients who have been previously treated with streptokinase, as there is a risk of anaphylaxis (life-threatening allergic reaction) due to the production of antibodies against the enzyme.

[edit] References

v • d • e Proteins: coagulation Coagulation factors Primary hemostasis vWF platelet membrane glycoproteins: Ib (A, B, IX) · IIb/IIIa (IIb, IIIa) · VI Intrinsic pathway HMWK/Bradykinin · Prekallikrein/Kallikrein · XII "Hageman" XI · IX · VIII Extrinsic pathway III "Tissue factor" · VII Common pathway X · V · II "(Pro)thrombin" · I "Fibrin" XIII Coagulation inhibitors Antithrombin (inhibits II, IX, X, XI, XII) · Protein C (inhibits V, VIII)/Protein S (cofactor for protein C) · Protein Z (inhibits X) · ZPI (inhibits X, XI) · TFPI (inhibits III) Thrombolysis/fibrinolysis Plasmin · tPA/urokinase · PAI-1/2 · α2-AP · α2-macroglobulin · TAFI