Fibrinolytic drugs

Key examples

• Alteplase
• Streptokinase

 

Common indications

1. In acute ischaemic stroke, alteplase increases the chance of living independently if it is given within 4.5 hours of the onset of the stroke.
2. In acute ST elevation myocardial infarction, alteplase and streptokinase can reduce mortality when they are given within 12 hours of the onset of symptoms in combination with antiplatelet agents and anticoagulants. However, primary percutaneous coronary intervention (where available) has largely superseded fibrinolytics in this context.
3. For massive pulmonary embolism with haemodynamic instability fibrinolytic drugs reduce clot size and pulmonary artery pressures, but there is no clear evidence that they improve mortality.

 

Mechanisms of action

• Fibrinolytic drugs, also known as thrombolytic drugs, catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots and re-canalise occluded vessels. 
• This allows reperfusion of affected tissue, preventing or limiting tissue infarction and cell death and improving patient outcomes.

 

Important adverse effects

• Common adverse effects include nausea and vomiting, bruising around the injection site and hypotension. 
• Adverse effects that require treatment to be stopped include serious bleeding, allergic reaction, cardiogenic shock and cardiac arrest. 
• Serious bleeding may require treatment with coagulation factors and antifibrinolytic drugs, e.g. tranexamic acid, but this is usually avoidable as fibrinolytic agents have a very short half-life. 
• Reperfusion of infarcted brain or heart tissue can lead to cerebral oedema and arrhythmias, respectively.

 

Warnings

• There are many contraindications to thrombolysis, which are mostly factors that predispose to bleeding including: recent haemorrhage; recent trauma or surgery; bleeding disorders; severe hypertension; and peptic ulcers. 
• In acute stroke, intracranial haemorrhage must be excluded with a CT scan before treatment. 
• Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytics can be used), as development of anti-streptokinase antibodies can block its effect.

 

Important interactions

• The risk of haemorrhage is increased in patients taking anticoagulants, and antiplatelet agents. 
• ACE inhibitors appear to increase the risk of anaphylactoid reactions.