What Is Thrombolytic Therapy?

  • Gregorio Anselmetti Bachelor of Science - BSc, Neuroscience. University of Warwick
  • Richa Lal MBBS, PG Anaesthesia, University of Mumbai, India

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When we get a wound from a fall or a cut, we tend to see blood and often experience pain from the site of injury. As time passes, you will notice that the bleeding has stopped and a rough surface of blood has formed over your cut, also known as a scab. What we are seeing is blood clotting in action, a vital physiological process that prevents blood loss, infection, and debris from entering wounds while they heal. 

Blood clots can cause serious complications and put people at risk of certain conditions like heart attacks, strokes, pulmonary embolism, and deep vein thrombosis (DVT) in certain circumstances. Thrombolytic therapy has been developed to break down blood clots that present a significant clinical risk. In this article, we will take a closer look at clots and life-saving thrombolytic therapy. 

What are blood clots?

A blood clot is essentially a clump that, under healthy conditions, acts to plug a wound, preventing blood loss and infection whilst allowing new skin or tissue to form underneath. Blood clots are made up of: 1

In medical terminology, a clot that has formed and remains in a vessel is known as a thrombus from the ancient Greek thrόmbos, while a clot that has detached and migrated around the body is an embolus. Thrombus can cause a risk of vessel occlusion, causing ischaemia, which is a restriction in blood supply to important organs and areas of the body, and the following complications can arise:

  • Heart attack/myocardial infarction
  • Stroke
  • Pulmonary Embolism
  • Deep vein thrombosis (DVT)
  • Kidney failure

How do blood clots form?

When a vessel wall becomes injured, certain proteins like collagen and tissue factor (TF) become exposed and activate platelets, the smallest of the cells that make up our blood, causing them to bind together and stick to the damaged vessel.2 The primary function of platelets is to respond to bleeding in the body, so when they attach, they can form an initial plug or clot, which acts to prevent blood loss from the wound.3

This further triggers certain other processes like the production of a key enzyme known as thrombin, which is responsible for converting fibrinogen to fibrin.4 Fibrinogen is usually inactive and circulating in the surrounding blood, but when it is converted to fibrin, it creates a mesh that traps the platelets and some red blood cells in the process providing rigidity and strengthening the clot.

Risk factors

Diet

According to the World Health Organisation, cardiovascular diseases, which include stroke and heart attack, are the leading cause of global death and disability. Heart attacks and strokes are forecast to continue to rise, and this is mainly due to current lifestyles, which increasingly involve high-fat, high-salt diets.5 Enjoying a treat now and again is enjoyable and often good for our mental well-being, but try to incorporate this into a well-balanced, nutritious diet brimming with fruits and vegetables. 

Pregnancy

Pregnancy can be a factor that can increase the likelihood of developing blood clots, as there are changes in the levels of clotting and anti-clotting proteins as the body prepares for blood loss during birth.6

Lifestyle

Lifestyle plays an important role in our overall health and vitality and is also something we can make efforts to improve. Aside from diet, it is advisable to stay hydrated, which helps to thin the blood, allowing it to flow freely throughout the body. Of course, some things exist that are out of our control, such as medical conditions that can increase clotting, but you can seek guidance on therapeutic strategies that can help to manage this. 

Additional risk factors include

  • Recent surgery
  • Bone breakages
  • Long periods without movement, such as a hospital stay
  • Overweight
  • Age– the risk of clots increases with age
  • Atrial fibrillation– a heart condition
  • Thrombophilia – a medical condition in which the blood can clot very easily
  • Genetic factors 

Blood clot symptoms

Depending on the area of the body affected the symptoms of blood clots can vary but often include:

  • Pain
  • Swelling/inflammation
  • Changes to skin colour
  • Edema– build-up of fluid
  • Chest pain
  • Cramp – if clot occurs in limbs
  • Sweating
  • Dizziness
  • Coughing
  • Vision problems
  •  Abdominal pain
  •  Blood in urine

If you are experiencing any of the above symptoms and suspect you may have a blood clot, you must contact a professional for the best course of action.

What is thrombolytic therapy?

Patients with cardiovascular diseases are often prescribed anticoagulant and antiplatelet medications which prevent clot formation and are preferred for longer-term management of health conditions, however, these are unable to treat clots that have already formed.

Thrombolytic therapy has been a life-saving breakthrough treatment for patients with potentially dangerous clots. They are a group of medications that can effectively dissolve blood clots restoring blood supply to the affected area. 

Thrombolytic therapy is also known as fibrinolytic therapy. These medications are usually given intravenously shortly after symptoms appear and are effective for treating pulmonary embolism, heart attack, stroke, and venous and arterial thrombosis.7 

How does thrombolytic therapy work?

Thrombolytic therapy refers to a group of medications known as plasminogen activators. Plasminogen is an inactive form of the enzyme plasmin, which belongs to a group of enzymes naturally produced by the liver that break down proteins.8 If you think of fibrin as a large net and plasmin as a pair of scissors used to cut the net into smaller pieces, this is similar to how plasmin breaks down the fibrin meshwork through breaking linkages in the protein structure.9 As a result, soluble fibrin products are produced, which no longer obstruct the blood vessel, and blood flow is restored.

Possible side effects

Patients who are treated with thrombolytic therapy will require prior assessment for individual bleeding risk. Thrombolytic therapy has improved over the years becoming more specific to problematic clots, however, the medication is not able to differentiate between dangerous thrombi and healthy fibrin plugs in the body. This means bleeding can occur and remains the most significant side effect of the treatment, with hemorrhagic stroke being the most extreme.10 There is also a risk of allergic reactions as well as high blood pressure in some patients.

Examples of thrombolytic medications

Currently, there is a range of thrombolytic agents available which will be recommended based on individual cases, below are some examples:

Clinical professionals will assess patients based on their situation, for example, Tenecteplase is recommended to be administered within 6 hours of presentation with symptoms, while other drugs can be given to patients within 12 hours of developing symptoms. Most thrombolytic therapies are known to be most effective given within a shorter time window.

FAQs

What is a blood clot?

A blood clot is like a mesh and it is the body's way of responding to wounds by acting like a plug to prevent excessive bleeding. They comprise red and white blood cells, platelets, and proteins like fibrin.

When do blood clots become dangerous?

If blood clots form without injury, it can indicate the presence of an underlying health condition. When clots break away from the site where they’ve developed and travel around the body, causing a blockage in a vessel, blood supply can be restricted to important organs and limbs. This can result in pain, inflammation, disability, and fatality if medical attention is not sought.

What is thrombolytic therapy?

Thrombolytic therapy relies on the enzyme action of the serine protease plasmin to break down and dissolve blood clots, forming soluble by-products and restoring blood flow to the affected area. This breakthrough treatment has helped to prevent disability and death of thousands of patients.

Is thrombolytic therapy dangerous?

All patients will be carefully assessed before any treatment, particularly those who are on anticoagulant medication, as this will increase the risk of bleeding as this therapy has its risks. In most severe cases, hemorrhagic stroke can occur. 

Summary

Clotting is an essential process in the body that prevents excessive bleeding and is necessary for our survival. When a person is at an increased risk of developing clots, or they arise without injury, it can present significant clinical risk, leading to pulmonary embolism, heart attacks, and stroke. Clot-related incidents are a global leading cause of disability and fatalities, and the development of appropriate treatments has been crucial. 

Thrombolytic therapy has been a key discovery, saving thousands of lives and preventing deleterious side effects. Thrombolytic agents are drugs that use serine protease enzymes to degrade blood clots into smaller soluble pieces, allowing blood to travel throughout the body providing life-sustaining nutrients and oxygen to surrounding tissues. If you see anyone or develop any blood clot symptoms, you must seek medical attention as soon as possible, as most thrombolytic drugs have the greatest efficacy when given to patients soon after discovering a blood clot.

References

  1. Lichota A, Szewczyk EM, Gwozdzinski K. Factors affecting the formation and treatment of thrombosis by natural and synthetic compounds. International Journal of Molecular Sciences [Internet]. 2020 Jan [cited 2023 Nov 29];21(21):7975. Available from: https://www.mdpi.com/1422-0067/21/21/7975 
  2. Zaidi A, Green L. Physiology of haemostasis. Anaesthesia & Intensive Care Medicine [Internet]. 2019 Mar 1 [cited 2023 Nov 29];20(3):152–8. Available from: https://www.sciencedirect.com/science/article/pii/S1472029919300050 
  3. van Kempen THS, Donders WP, van de Vosse FN, Peters GWM. A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behaviour Biomech Model Mechanobiol [Internet]. 2016 Apr 1 [cited 2023 Nov 29];15(2):279–91. Available from: https://doi.org/10.1007/s10237-015-0686-9
  4. Al-Amer OM. The role of thrombin in haemostasis. Blood Coagulation & Fibrinolysis [Internet]. 2022 Apr [cited 2023 Nov 29];33(3):145. Available from: https://journals.lww.com/bloodcoagulation/Fulltext/2022/04000/The_role_of_thrombin_in_haemostasis.1.aspx
  5. Violi F, Pastori D, Pignatelli P, Carnevale R. Nutrition, thrombosis, and cardiovascular disease. Circ Res [Internet]. 2020 May 8 [cited 2023 Nov 29];126(10):1415–42. Available from: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.315892
  6. Su X, Zhao W. Platelet aggregation in normal pregnancy. Clinica Chimica Acta [Internet]. 2022 [cited 2024 May 7]; 536:94–7. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0009898122013055.
  7. Ali MR, Salim Hossain M, Islam MA, Saiful Islam Arman M, Sarwar Raju G, Dasgupta P, et al. Aspect of thrombolytic therapy: a review. The Scientific World Journal [Internet]. 2014 Dec 10 [cited 2023 Nov 29];2014:e586510. Available from: https://www.hindawi.com/journals/tswj/2014/586510/
  8. Baig MU, Bodle J. Thrombolytic therapy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557411/
  9. Jilani TN, Siddiqui AH. Tissue plasminogen activator. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 30]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK507917/
  10. Kluft C, Sidelmann JJ, Gram JB. Assessing safety of thrombolytic therapy. Semin Thromb Hemost [Internet]. 2017 Apr [cited 2023 Dec 1];43(3):300–10. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0036-1584130

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Pippa Chapman

MSc, Immunology, University of Strathclyde

Pippa is a Cell Culture Scientist who after completing an MSc in Immunology has been employed in the biotechnology sector. She has a strong interest in medical research and the application of both conventional and holistic strategies to tackle today's most challenging health conditions.

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