Overview

In a medical emergency, the understanding and use of thrombolysis can be the difference between life and death. If you are looking for a guide on how thrombolysis works, you are in the right place. This article will go over the use of clot-dissolving medications and their use in emergencies.  

What is thrombolysis?

Thrombolysis, known as thrombolytic treatment or fibrinolytic therapy, is a group of medicines used to dissolve dangerous blood clots in the blood vessels that stop blood flow and oxygen from reaching certain body parts.¹

These medicines are known as clot-dissolving drugs (also called thrombolytics or fibrinolytics) and are used to treat a variety of different diseases, such as heart attack and stroke.¹

Why is thrombolysis important in medical emergencies?

Thrombolytic treatment is important in emergencies as it dissolves blood clots that stop blood flow and oxygen supply to tissues.^1,2 By dissolving these blood clots, blood circulation can continue to vital organs, decreasing the risk of organ damage.^1,2

Thrombolytics have been shown to be very effective in lowering the death rate, and there have been several studies done which support this.²

How do thrombolytics work?

During thrombosis, the process in which blood clots are formed, a protein called fibrin forms a spider web-type structure, trapping platelets and other blood cells, resulting in a blood clot.¹ Therefore, disrupting fibrin would break this spider web-like structure, causing the blood clot to break down.¹ 

How is fibrin broken down?

Plasminogen, an inactive protein, is converted into plasmin, an active protein, which breaks down fibrin when it is bound to it.¹ This breakdown of fibrin, therefore, dissolves blood clots.¹ Plasminogen can also bind to a protein called urokinase to turn into plasmin and break down fibrin.¹

There are 2 main categories of thrombolytics.¹ This is dependent on how they work:

• Fibrin-specific agents- these agents need fibrin to bind to, so the active protein plasmin can be formed, which can help break down blood clots
• Non-fibrin-specific agents- these agents can form plasmin without the need to bind to fibrin, affecting plasminogen within clots and in the general circulation indiscriminately¹

What are some thrombolytics?

There are several thrombolytics that are currently used.¹ These include:¹

Fibrin-specific agents

• Alteplase
• Tenecteplase
• Reteplase
• Prourokinase

Non-fibrin-specific agents

• Streptokinase
• Urokinase
• Anistreplase

Fibrin-specific agents

Alteplase

Alteplase is fibrin-specific, so it targets fibrin that is bound to plasminogen in the clot.¹ This drug is effective, though there is a moderate chance of bleeding, as it breaks down a substantial amount of fibrin.¹ 

Tenecteplase

Tenecteplase works similarly to alteplase, and it has a lower risk of bleeding than alteplase as it only binds to the surface of the blood clot.¹

Reteplase

Reteplase has weak binding with fibrin, which allows diffusion through a blood clot rather than binding only at the surface, like Tenecteplase, for example.¹ Reteplase allows the conversion of plasminogen into plasmin throughout the blood clot, causing it to work faster.¹

Prourokinase

Prourokinase needs urokinase to activate it to work.¹ Urokinase turns plasminogen into plasmin within the blood clot, making prourokinase fibrin-dependent.¹

This is a newer treatment that is currently going through clinical trials.¹

Non-fibrin-specific agents

Streptokinase

Streptokinase is a widely used thrombolytic, as it is low-cost and has good safety and effectiveness.¹  

It works by binding to plasminogen and forming a complex, which is then converted into plasmin, breaking down clots.¹ However, streptokinase is dependent on free circulating plasminogen throughout the bloodstream and not just at the clot, so this decreases its efficiency.¹ This also causes a higher risk of unwanted bleeding.¹

The risk of using streptokinase is that it comes from the bacteria streptococcus, so there is a higher chance of allergic reactions, and it is unsafe to use more than once in six months.^!

Urokinase

Urokinase is a thrombolytic that was originally purified from human urine, but it is now mainly manufactured via in vitro cell culture and is now available commercially.¹ It is commonly used as it is effective and low-cost.¹

It works by directly turning plasminogen into plasmin, which leads to the breakdown of blood clots.¹

Anistreplase

Anistreplase is a mixture of streptokinase and plasminogen, so it does not depend on free circulating plasminogen alone like streptokinase.¹

How are thrombolytics given?

Thrombolytics are given in two ways.¹ This includes systemic administration through a peripheral IV and local administration by a catheter at the clot site.

Systemic administration

Systemic administration through a peripheral IV is when a small tube is inserted into the vein and medicine is delivered into your bloodstream.^1,3 By doing this, the medicine can work quickly through the body, which is vital in emergencies.^1,2,3  

Local administration

Local administration by a catheter at the clot site is done to specifically target the blood clot. This is done by using a catheter, which is a tube that is inserted into the blood vessel where the clot is.^1,3 A thrombolytic drug is then delivered into the body through the catheter directly where it is needed.^1,3

This is done so the thrombolytic can reach a specific site, minimising the risk of systemic bleeding and postthrombotic syndrome (PTS).  Catheterisation can be useful in emergencies, such as when the chance of loss of limb is high.

In what circumstances are thrombolytics used?

• Acute myocardial infarction
• Acute ischaemic stroke
• Deep vein thrombosis and Pulmonary embolism
• Catheter occlusion

Acute myocardial infarction

Acute myocardial infarction, otherwise known as a heart attack, can be treated with thrombolytic therapy.¹ It is very important to deliver the thrombolytic therapy as quickly as possible, as the longer you wait, the less effective the treatment will be.¹

The thrombolytics are given to the heart attack sufferer through IV within a few minutes, depending on what agent is used.¹

Tenecteplase is given through a single IV over a period of 5 seconds, and it is the preferred method for heart attack as it can be done very quickly, which is crucial for the best chance of recovery.¹

Acute ischaemic stroke

Acute ischaemic stroke is when a blood clot blocks an artery that goes to the brain, causing the blockage of blood and oxygen to the brain, leading to brain damage.⁴

Treatment for stroke being done as soon as possible is very important, and the longer the brain is blocked from blood and oxygen, the more brain damage will occur.¹

Alteplase is the most commonly used thrombolytic for stroke as it improves the symptoms significantly within a few hours of being used.¹

Deep vein thrombosis and pulmonary embolism

Deep vein thrombosis is when a blood clot forms in a deep vein, commonly occurring in the legs.¹ Thrombolytic treatment is often used to help break down the blood clot and restore blood flow and oxygen in the affected legs.^1,5

Deep vein thrombosis can lead to pulmonary embolism, which is the blockage of a pulmonary artery in the lungs, from a blood clot that came from the lower limbs, i.e. a leg.^1,6 

The most commonly used thrombolytic agent to treat pulmonary embolism is alteplase, through IV over a period of 2 hours.¹

It is recommended that thrombolytic therapy be started as quickly as possible if the person with pulmonary embolism has a low bleeding risk and low blood pressure due to the risk of cardiogenic shock.¹

Catheter occlusion

Catheter occlusion is when a catheter is blocked or obstructed. This can lead to symptoms such as oedema.⁷

Urokinase and alteplase are commonly used to treat catheter obstruction⁷.

Possible side effects

As with every medicine, there are side effects. With thrombolytic agents, the most common side effects are bleeding, allergic reactions and low blood pressure.¹ Streptokinase, in particular, is known for its side effects.¹

Monitoring during/after thrombolytic treatment

Due to the possible side effects of thrombolytics, monitoring people who have received this therapy is crucial.¹ Blood pressure and bleeding, in particular, are monitored closely to prevent any complications.¹

Conclusion

Thrombolysis, also known as thrombolytic treatment, is a group of medicines used to dissolve blood clots that can cause life-threatening conditions such as myocardial infarction, ischaemic stroke, deep vein thrombosis, pulmonary embolism and catheter occlusion. Thrombolysis is important in medical emergencies as dissolving blood clots in a timely manner decreases damage caused by a lack of blood and oxygen in vital organs.  They work by breaking down fibrin, which, in turn, leads to the breakdown of blood clots. There are 2 main types: fibrin-specific thrombolytics, which include alteplase, tenecteplase, reteplase, and prourokinase and non-fibrin-specific agents, which include streptokinase, urokinase, and anistreplase. Which thrombolytic treatment is used depends on the disease and a person’s needs. There are also varying side effects, and people being treated with thrombolytics must be monitored closely to avoid complications.

Overall, thrombolytics are crucial in life-saving treatment when it comes to blood clot-related diseases, as the time taken to treat blood clot-related illnesses can be a matter of life and death.