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).

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:

Apart from streptokinase, all thrombolytic drugs are administered together with heparin (unfractionated or low molecular weight heparin), usually for 24 to 48 hours.[ citation needed ]

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). [7]

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.

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.

Myocardial infarction

Absolute contraindications: [8]

Relative contraindications: [8]

Stroke

Absolute contraindications: [9]

Relative contraindications: [10]

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.

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.

Some fibrinolytics are:

Research

In people who receive thrombolytic therapy delivered through a catheter, 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. [14]

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 anticoagulants have little effect.

Thrombosis Vascular disease caused by the formation of a blood clot inside a blood vessel

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.

Thrombus

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 prevent bleeding, but can be harmful in thrombosis, when clots obstruct blood flow through healthy blood vessels.

Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis. The primary type is a normal body process, whereas secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.

Ischemia Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to tissues, 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. It also means local anemia in a given part of a body sometimes resulting from constriction. Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial or total.

Tissue plasminogen activator Mammalian protein found in Homo sapiens

Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Human tPA has a molecular weight of ~70 kDa in the single-chain form.

Stroke Death of a region of brain cells due to poor blood flow

A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control.

Streptokinase

Streptokinase (SK) is a thrombolytic medication and enzyme. 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.

Alteplase

Alteplase (t-PA) 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. It is given by injection into a vein or artery. Alteplase is the same as the normal human plasminogen activator and is synthesized via recombinant DNA technology from vascular endothelial cells. Alteplase causes the breakdown of a clot by inducing fibrinolysis.

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.

Cerebral infarction

A cerebral infarction is an area of necrotic tissue in the brain resulting from a blockage or narrowing in the arteries supplying blood and oxygen to the brain. The restricted oxygen due to the restricted blood supply causes an ischemic stroke that can result in an infarction if the blood flow is not restored within a relatively short period of time. The blockage can be due to a thrombus, an embolus or an atheromatous stenosis of one or more arteries. Which arteries are problematic will determine which areas of the brain are affected (infarcted). These varying infarcts will produce different symptoms and outcomes. About one third will prove fatal.

Ultrasound-enhanced systemic thrombolysis (UEST) is a medical technology that uses ultrasound to enhance the effects of thrombolytic drugs. To treat the blood clots causing strokes, transcranial Doppler ultrasonography is used. It is thought that transcranial doppler ultrasonography aimed at residual obstructive intracranial blood flow may help expose thrombi to tissue plasminogen activator or other thrombolytic drugs.

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.

Désiré Collen 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.

Vorapaxar

Vorapaxar is a thrombin receptor antagonist based on the natural product himbacine, discovered by Schering-Plough and developed by Merck & Co.

Embolectomy is the emergency surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi, and is then referred to as 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.

Acute limb ischaemia 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.

Reperfusion therapy

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), followed by a coronary angioplasty. The angioplasty uses the insertion of a balloon to open up the artery, with the possible additional use of one or more stents. Other surgeries performed are the more invasive bypass surgeries that graft arteries around blockages.

Arterial embolism 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.

Management of acute coronary syndrome is targeted against the effects of reduced blood flow to the afflicted 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 (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.
  4. ↑ Mistry EA (2017). "Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis". Stroke. 48 (9): 2450–2456. doi:10.1161/STROKEAHA.117.017320. PMID   28747462.
  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.CS1 maint: multiple names: authors list (link)
  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. PMID   30739331.
  7. ↑ 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.CS1 maint: uses authors parameter (link)
  8. 1 2 Harvey D. White; Frans J. J. Van de Werf (1998). "Clinical Cardiology: New Frontiers Thrombolysis for Acute Myocardial Infarction". Circulation. 97 (16): 1632–1646. doi: 10.1161/01.CIR.97.16.1632 . PMID   9593569.CS1 maint: multiple names: authors list (link)
  9. ↑ 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.
  10. ↑ Jason Thurman; Edward C. Jauch (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.
  11. 1 2 3 "Therapeutic Biologic Applications (BLA) > Difficulties in Obtaining Sufficient Amounts of Urokinase (Abbokinase)". US Food and Drug Administration. 10/07/2016. Retrieved 2016-12-28.Check date values in: |date= (help)
  12. 1 2 "Therapeutic Biologics Applications (BLA)". US Food and Drug Administration. 07-10- 2016. Retrieved 2016-12-28.Check date values in: |date= (help)
  13. ↑ "Urokinase". www.drugbank.ca. Retrieved 17 March 2019.
  14. ↑ 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): 1519–1527.e26. doi: 10.1016/j.jvs.2016.11.025 . ISSN   1097-6809. PMID   28274749.
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