Thrombolysis

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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.

Contents 1 Agents 2 Principles 3 Uses 4 Contraindications 5 References 6 Trivia

[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
• Cerebrovascular accident
• Massive pulmonary embolism
• Acute limb ischaemia

While the use of thrombolytic drugs can lyse an embolus to improve right ventricular function or pulmonary perfusion, it is also associated with an increased risk of major hemorrhage. The clinician should judge the use of this class of drugs on a case by case basis.

[edit] Contraindications

These are contraindicated in bleeding disorders, active bleeding and when there has been recent surgery. Diabetic retinopathy is a relative contraindication. Although thrombolysis has been available for years in the treatment of heart attacks, it is now most important in the early treatment of strokes. Ischemic strokes which are caused by arterial occlusion can now be treated with recombinant tissue plasminogen activator (rtPA). The FDA has approved the use of rtPA within 3 (three) hours of onset of ischemic stroke. Many centres also use rtPA for intra arterial thrombolysis (IAT) when patients present with stroke beyond three hours. Although the upper limit is poorly defined, especially when it comes to occlusion of posterior circulation vessels, most IAT is conventionally performed between 3 to 6 hours of stroke onset.

[edit] References

• Wardlaw JM, Zoppo G, Yamaguchi T, Berge E (2003). "Thrombolysis for acute ischaemic stroke". Cochrane Database Syst Rev (3): CD000213. PMID 12917889. 

[edit] Trivia

Tony Blair, in a speech, was unable to pronounce the word "thrombolysis". He responded to the laughter at his mistake with "and I'm the guy running the country."