Thrombolysis

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Thrombolysis
Angiograph before and after thrombolytic therapy in a case of thrombosis on the hand.png
Angiograph before and after thrombolytic therapy in a case of acute limb ischemia.
Other namesFibrinolytic therapy
MedlinePlus 007089
eMedicine 811234

Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive pulmonary embolism or extensive deep vein thrombosis).[ citation needed ]

Contents

The main complication is bleeding (which can be dangerous), and in some situations thrombolysis may therefore be unsuitable. Thrombolysis can also play an important part in reperfusion therapy that deals specifically with blocked arteries.

Medical uses

Diseases where thrombolysis is used:

Thrombolysis is usually intravenous. It may also be used directly into the affected blood vessel during an angiogram (intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours or in severe deep vein thrombosis (catheter-directed thrombolysis). [9]

Thrombolysis is performed by many types of medical specialists, including interventional radiologists, vascular surgeons, cardiologists, interventional neuroradiologists, and neurosurgeons. In some countries such as the United States of America, emergency medical technicians may administer thrombolytics for heart attacks in prehospital settings, by on-line medical direction. In countries with more extensive and independent qualifications, prehospital thrombolysis (fibrinolysis) may be initiated by the emergency care practitioner (ECP). Other countries which employ ECP's include, South Africa, the United Kingdom, and New Zealand. Prehospital thrombolysis is always the result of a risk-benefit calculation of the heart attack, thrombolysis risks, and primary percutaneous coronary intervention (pPCI) availability.[ citation needed ]

Contraindications

Thrombolysis is not without risks. Therefore, clinicians must select patients who are to be best suited for the procedure, and those who have the least risk of having a fatal complication. An absolute contraindication is in itself enough to avoid thrombolysis, while a relative contraindication needs to be considered in relation to the overall clinical situation.[ citation needed ]

Myocardial infarction

Absolute contraindications: [10]

Relative contraindications: [10]

Stroke

Absolute contraindications: [11] [12]

Relative contraindications: [13]

Side-effects

Hemorrhagic stroke is a rare but serious complication of thrombolytic therapy. If a patient has had thrombolysis before, an allergy against the thrombolytic drug may have developed (especially after streptokinase). If the symptoms are mild, the infusion is stopped and the patient is commenced on an antihistamine before infusion is recommenced. Anaphylaxis generally requires immediate cessation of thrombolysis.[ citation needed ]

Agents

Thrombolysis therapy uses thrombolytic drugs that dissolve blood clots. Most of these drugs target fibrin (one of the main constituent of blood clots) and are therefore called fibrinolytics. All currently approved thrombolytic drugs are biologics, either derived from Streptococcus species, or, more recently, using recombinant biotechnology whereby tPA is manufactured using cell culture, resulting in a recombinant tissue plasminogen activator or rtPA.[ citation needed ]

Some fibrinolytics are:

Catheter-directed thrombolysis

A 2023 meta-analysis of 44 studies [17] compared treatments for pulmonary embolism including thrombolytic therapy delivered through a catheter. Catheter-directed thrombolysis (CDT) methods included fragmentation and ultrasound use. CDT was associated with better outcomes than anticoagulation alone or systemic thrombolysis, but the studies were mostly small and observational.

In people who receive CDT, there is a risk of hemorrhage as a side effect. Scientists have studied whether measuring fibrinogen in blood can be used as a biomarker to predict hemorrhage. As of 2017 it was not known if this works or not. [18]

Research

Researchers showed a 10-fold variation in the proportion of patients who received thrombolysis after stroke in England and Wales, ranging from 1 in 50 (2%) to 1 in 4 (24%). The team also showed that most of the variation was explained by hospital processes (such as how quickly people can have a brain scan) and in doctors’ decision-making (who they think should or should not receive thrombolysis) rather than knowledge of the time of stroke. [19] [20]

Prospective, randomized clinical trials to evaluate the utility of catheter-directed thrombolysis in pulmonary embolism include HI-PEITHO (Higher-Risk Pulmonary Embolism Thrombolysis). [21]

See also

Related Research Articles

An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where classical Vitamin K antagonist anticoagulants have minimal effect.

<span class="mw-page-title-main">Thrombosis</span> Formation of blood clots inside the blood vessels

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

<span class="mw-page-title-main">Thrombus</span> Blood clot

A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system.

<span class="mw-page-title-main">Pulmonary embolism</span> Blockage of an artery in the lungs

Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. Symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. Signs of a PE include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. Severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death.

Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.

<span class="mw-page-title-main">Ischemia</span> Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also implies local hypoxia in a part of a body resulting from constriction.

<span class="mw-page-title-main">Tissue-type plasminogen activator</span> Protein involved in the breakdown of blood clots

Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots. It acts as an enzyme to convert plasminogen into its active form plasmin, the major enzyme responsible for clot breakdown. It is a serine protease found on endothelial cells lining the blood vessels. Human tPA is encoded by the PLAT gene, and has a molecular weight of ~70 kDa in the single-chain form.

<span class="mw-page-title-main">Thromboembolism</span> Obstruction of a blood vessel by a clot

Thromboembolism is a condition in which a blood clot (thrombus) breaks off from its original site and travels through the bloodstream to obstruct a blood vessel, causing tissue ischemia and organ damage. Thromboembolism can affect both the venous and arterial systems, with different clinical manifestations and management strategies.

<span class="mw-page-title-main">Streptokinase</span> Pharmaceutical drug

Streptokinase is a thrombolytic medication activating plasminogen by nonenzymatic mechanism. As a medication it is used to break down clots in some cases of myocardial infarction, pulmonary embolism, and arterial thromboembolism. The type of heart attack it is used in is an ST elevation myocardial infarction (STEMI). It is given by injection into a vein.

<span class="mw-page-title-main">Alteplase</span> Thrombolytic medication

Alteplase, sold under the brand name Activase among others, is a biosynthetic form of human tissue-type plasminogen activator (t-PA). It is a thrombolytic medication used to treat acute ischemic stroke, acute ST-elevation myocardial infarction, pulmonary embolism associated with low blood pressure, and blocked central venous catheter. Alteplase is given by injection into a vein or artery. Alteplase is the same as the normal human plasminogen activator produced in vascular endothelial cells and is synthesized via recombinant DNA technology in Chinese hamster ovary cells (CHO). Alteplase causes the breakdown of a clot by inducing fibrinolysis.

<span class="mw-page-title-main">Desmoteplase</span> Medication

Desmoteplase is a novel, highly fibrin-specific "clot-busting" (thrombolytic) drug in development that reached phase III clinical trials. The Danish pharmaceutical company, Lundbeck, owns the worldwide rights to Desmoteplase. In 2009, two large trials were started to test it as a safe and effective treatment for patients with acute ischaemic stroke. After disappointing results in DIAS-3, DIAS-4 was terminated, and in December 2014 Lundbeck announced that they would stop the development of desmoteplase.

An embolus, is described as a free-floating mass, located inside blood vessels that can travel from one site in the blood stream to another. An embolus can be made up of solid, liquid, or gas. Once these masses get "stuck" in a different blood vessel, it is then known as an "embolism." An embolism can cause ischemia—damage to an organ from lack of oxygen. A paradoxical embolism is a specific type of embolism in which the embolus travels from the right side of the heart to the left side of the heart and lodges itself in a blood vessel known as an artery. Thus, it is termed "paradoxical" because the embolus lands in an artery, rather than a vein.

Ancrod is a defibrinogenating agent derived from the venom of the Malayan pit viper. Defibrinogenating blood produces an anticoagulant effect. Ancrod is not approved or marketed in any country. It is a thrombin-like serine protease.

<span class="mw-page-title-main">Désiré Collen</span> Belgian chemist, physician

Désiré, Baron Collen is a Belgian physician, chemist, biotechnology entrepreneur and life science investor. He made several discoveries in thrombosis, haemostasis and vascular biology in many of which serendipity played a significant role. His main achievement has been his role in the development of tissue-type plasminogen activator (t-PA) from a laboratory concept to a life-saving drug for dissolving blood clots causing acute myocardial infarction or acute ischemic stroke. Recombinant t-PA was produced and marketed by Genentech Inc as Activase and by Boehringer Ingelheim GmbH as Actilyse, and is considered biotechnology's first life saving drug.

Embolectomy is the emergency interventional or surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi, and is then referred to as thromboembolectomy or thrombectomy. Embolectomy is an emergency procedure often as the last resort because permanent occlusion of a significant blood flow to an organ leads to necrosis. Other involved therapeutic options are anticoagulation and thrombolysis.

<span class="mw-page-title-main">Acute limb ischaemia</span> Occurs when there is a sudden lack of blood flow to a limb

Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb, within 14 days of symptoms onset. On the other hand, when the symptoms exceed 14 days, it is called chronic limb ischemia (CLI). CLI is the end stage of peripheral vascular disease where there is still some collateral circulation that bring some blood flow to the distal parts of the limbs. While limbs in both acute and chronic limb ischemia may be pulseless, a chronically ischemic limb is typically warm and pink due to a well-developed collateral artery network and does not need emergency intervention to avoid limb loss, whereas ALI is a vascular emergency.

<span class="mw-page-title-main">Reperfusion therapy</span> Restoring blood flow post-heart attack

Reperfusion therapy is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack. Reperfusion therapy includes drugs and surgery. The drugs are thrombolytics and fibrinolytics used in a process called thrombolysis. Surgeries performed may be minimally-invasive endovascular procedures such as a percutaneous coronary intervention (PCI), which involves coronary angioplasty. The angioplasty uses the insertion of a balloon and/or stents to open up the artery. Other surgeries performed are the more invasive bypass surgeries that graft arteries around blockages.

<span class="mw-page-title-main">Arterial embolism</span> Interruption of blood flow to an organ

Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmonary embolism is classified as arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins. Arterial embolism is the major cause of infarction.

<span class="mw-page-title-main">Management of acute coronary syndrome</span>

Management of acute coronary syndrome is targeted against the effects of reduced blood flow to the affected area of the heart muscle, usually because of a blood clot in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve chest pain and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed. Basic principles of management are the same for all types of acute coronary syndrome. However, some important aspects of treatment depend on the presence or absence of elevation of the ST segment on the electrocardiogram, which classifies cases upon presentation to either ST segment elevation myocardial infarction (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes unstable angina and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and reperfusion therapy is more often reserved for them. Long-term therapy is necessary for prevention of recurrent events and complications.

References

  1. "Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group". Lancet. 343 (8893): 311–22. 5 February 1994. doi:10.1016/s0140-6736(94)91161-4. PMID   7905143.
  2. Wardlaw JM, Murray V, Berge E, Del Zoppo GJ (2014). "Thrombolysis for acute ischaemic stroke". Cochrane Database Syst Rev. 2016 (7): CD000213. doi:10.1002/14651858.CD000213.pub3. PMC   4153726 . PMID   25072528.
  3. Wechsler LR (2011). "Intravenous thrombolytic therapy for acute ischemic stroke". N Engl J Med. 364 (22): 2138–46. doi:10.1056/NEJMct1007370. PMID   21631326. S2CID   18769949.
  4. Mistry EA (2017). "Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis". Stroke. 48 (9): 2450–6. doi: 10.1161/STROKEAHA.117.017320 . PMID   28747462. S2CID   3751956.
  5. Kuo WT, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hofmann LV (November 2009). "Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques". J Vasc Interv Radiol. 20 (11): 1431–40. doi:10.1016/j.jvir.2009.08.002. PMID   19875060.
  6. Tran HA, Gibbs H, Merriman E, Curnow JL, Young L, Bennett A, Tan C, Chunilal SD, Ward CM, Baker R, Nandurkar H (March 2019). "New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism". The Medical Journal of Australia. 210 (5): 227–235. doi:10.5694/mja2.50004. hdl: 11343/285435 . PMID   30739331. S2CID   73433650.
  7. "Acute Limb Ischemia". The Lecturio Medical Concept Library. Retrieved 11 August 2021.
  8. Light, RW (2013). "Chapter 1: Anatomy of the Pleura". Pleural Diseases (6th ed.). Lippincott Williams & Wilkins. pp. 1–7. ISBN   978-1-4511-7599-8.
  9. Catanese L, Tarsia J, Fisher M (3 February 2017). "Acute Ischemic Stroke Therapy Overview". Circ Res. 120 (3): 541–558. doi: 10.1161/CIRCRESAHA.116.309278 . PMID   28154103.
  10. 1 2 White, Harvey D.; Van de Werf, Frans JJ. (1998). "Clinical Cardiology: New Frontiers Thrombolysis for Acute Myocardial Infarction". Circulation. 97 (16): 1632–46. doi: 10.1161/01.CIR.97.16.1632 . PMID   9593569.
  11. Department of Health, Western Australia. "Protocol for Administering Alteplase in Acute Ischaemic Stroke Guidelines" (PDF). Perth: Health Networks Branch, Department of Health, Western Australia. Retrieved 12 June 2013.
  12. WA Stroke Clinical Advisory Group (October 2022). "Protocol for Intravenous Thrombolysis in Acute Ischaemic Stroke" (PDF). Department of Health, State of Western Australia.
  13. Thurman, Jason; Jauch, Edward C. (2002). "Acute ischemic stroke: emergent evaluation and management". Emergency Medicine Clinics of North America. 20 (3): 609–630. doi:10.1016/s0733-8627(02)00014-7. PMID   12379964.
  14. 1 2 3 "Therapeutic Biologic Applications (BLA) > Difficulties in Obtaining Sufficient Amounts of Urokinase (Abbokinase)". US Food and Drug Administration. 4 October 2016 [11 December 1998]. Archived from the original on 18 January 2017. Retrieved 28 December 2016.
  15. "Urokinase". www.drugbank.ca. Retrieved 17 March 2019.
  16. 1 2 "Therapeutic Biologics Applications (BLA)". US Food and Drug Administration. 24 February 2020. Retrieved 28 December 2016.
  17. Planer D, Yanko S, Matok I, Paltiel O, Zmiro R, Rotshild V, Amir O, Elbaz-Greener G, Raccah BH (June 2023). "Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis". CMAJ. 195 (24): E833–43. doi:10.1503/cmaj.220960. PMC   10281204 . PMID   37336568.
  18. Poorthuis, Michiel H. F.; Brand, Eelco C.; Hazenberg, Constantijn E. V. B.; Schutgens, Roger E. G.; Westerink, Jan; Moll, Frans L.; de Borst, Gert J. (5 March 2017). "Plasma fibrinogen level as a potential predictor of hemorrhagic complications after catheter-directed thrombolysis for peripheral arterial occlusions". Journal of Vascular Surgery. 65 (5): 1519–27. doi: 10.1016/j.jvs.2016.11.025 . ISSN   1097-6809. PMID   28274749.
  19. Allen, Michael; James, Charlotte; Frost, Julia; Liabo, Kristin; Pearn, Kerry; Monks, Thomas; Zhelev, Zhivko; Logan, Stuart; Everson, Richard; James, Martin; Stein, Ken (21 October 2022). "Using simulation and machine learning to maximise the benefit of intravenous thrombolysis in acute stroke in England and Wales: the SAMueL modelling and qualitative study". Health and Social Care Delivery Research. 10 (31): 1–148. doi:10.3310/GVZL5699. hdl: 10871/131624 .
  20. "Increasing thrombolysis use after stroke: lessons from machine learning". NIHR Evidence. 5 July 2023. doi:10.3310/nihrevidence_58696.
  21. Klok FA, Piazza G, Sharp AS, Ní Ainle F, Jaff MR, Chauhan N, Patel B, Barco S, Goldhaber SZ, Kucher N, Lang IM, Schmidtmann I, Sterling KM, Becker D, Martin N, Rosenfield K, Konstantinides SV (September 2022). "Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study". Am Heart J. 251: 43–53. doi:10.1016/j.ahj.2022.05.011. hdl: 1887/3494555 . PMID   35588898.