Thrombolytic agents are used to lyse already formed blood clots in clinical settings where ischemia may be fatal ( acute mycardial infarction, pulmonary embolism, ischemic stroke, and arterial thrombosis). Very precise indications rule the use of these drugs, which are not free from serious side effects ( bleeding).
- Mechanism of action of thrombolytic therapy
- Animation on fibrinolysis
- List of thrombolytic drugs
- Side effects
The image below shows how serine protease thrombin (also called activated factor II) converts fibrinogen to fibrin.
Fibrin polymerizes and constitutes a “mesh” that acts as hemostatic clot (in conjunction with platelets) over a wounded site.
This plasmin meshwork can be cleaved by plasmin, which derives from an inactive precursor: plasminogen.
Plasminogen can be activated by the tissue plasminogen activator (t-PA), which is released by endothelial cells.
As can be seen in the image, streptokinase acts by activating plasminogen conversion into plasmin, which promotes clot lysis.
Since streptokinase is a protein obtained from Streptococci cultures, it is capable of eliciting antigenic responses in humans.
The following animation integrates the concepts previously explained, showing how endothelial cells release t-PA.
|Streptokinase (Streptase)||SK||Streptococcal culture|
|Urokinase||UK||Renal cell culture|
|Alteplase or Tissue plasminogen activator(trade names Retavase, Rapilysin)||t-PA||Recombinant technology|
|Anistreplase or Acylated plasminogen: streptokinase activator)||APSAC||Streptococcal|
|Prourokinase or Single-chain urokinase plasminogen activator||SCU-PA||Renal cell culture|
Streptokinase is a protein produced by Beta-hemolytic streptococci as a component of that organism tissue destroying machinery.
There are two drawbacks for streptokinase therapy:
- Previous administration of the drug is a contraindication, because of the risk of anaphylaxis.
- The thrombolytic actions are relatively nonspecific and can result in systemic fibrinolysis.
Since t-PA is produced by endothelial cells, it is nonantigenic and causes a more selective thrombolysis than streptokinase. Alteplase, the recombinant t-PA, is produced by recombinant DNA technology. It is effective in recanalizing occluded coronary arteries, limiting cardiac dysfunction and reducing mortality following an ST elevation myocardial infarction. At pharmacologic doses it can trigger a systemic lytic state and cause unwanted bleeding.
A genetically engineered variant of t-PA. Tecneplase has a longer half life than t-PA which allows it to be administered as a single weight-based bolus.
It has an increased half life than t-PA and increased specificity for fibrin. Its efficacy and adverse effect profile are similar to those of streptokinase and t-PA.
|Streptokinase||ST elevation myocardial infarction.Arterial thrombosis.
Deep vein thrombosis.
Intra-arterial or intravenous catheter occlusion.
|t-PA||Acute myocardial infarction.Acute cerebrovascular thrombosis.
Central venous catheter occlusion
|Tenecteplase (TNK) and reteplase||Acute myocardial infarction|
Adverse effects common to all agents of the class:
- Major bleeding.
- Cardiac arrhythmias.
- Cholesterol embolus syndrome.
- Anaphylactoid reaction.
- Cerebrovascular accident.
- Intracraneal hemorrhage.
Steptokinase adverse effects:
- Non-cardiogenic pulmonary edema.
- Fever and shivering.
- History of cerebrovascular hemorrhage at any time.
- Nonhemorrhagic stroke or other cerebrovascular event within the past year.
- Marked hypertension ( reliably determined systolic arterial pressure >180 mmHg and/or a diastolic pressure >110 mmHg) at any time during presentation.
- Suspicion of aortic dissection.
- Active internal bleeding (excluding menses).
Relative contraindications to thrombolytic therapy
- Current use of anticoagulats (INR 2).
- A recent (<2 weeks) invasive or surgical procedure or prolonged (10 min) cardiopulmonaty resuscitation .
- Known bleeding diathesis.
- Hemorrhagic ophthalmic condition.
- Active peptic ulcer disease.
- History of severe hypertension that is currently adequately controlled.
Harvey, Richard; Champe, Pamela (series editors). “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.
Lullmann, Heinz; Mohr Klaus. “Color Atlas of Pharmacology”, 2nd edition. Thieme: 1999.
Golan, David E (editor). “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”, 2nd edition. LWW: 2008.
Fauci, Anthony S., Braunwald, Eugene, Kasper,Dennis L. “Harrison’s Principles of Internal Medicine”, 17 edition. Mc Graw Hill: 2008.