Thrombolysis
Encyclopedia
Thrombolysis is the breakdown (lysis) of blood clots
by pharmacological
means. It is colloquially referred to as clot busting for this reason. It works by stimulating fibrinolysis
by plasmin
through infusion of analogs of tissue plasminogen activator
(tPA), the protein that normally activates plasmin.
s, which are either derived from Streptomyces
species, or, more recently, using recombinant
biotechnology whereby tPA is manufactured by bacteria
, resulting in a recombinant tissue plasminogen activator or rtPA.
Some commonly used thrombolytics are:
s (such as heparin
) decrease the "growth" of a clot, thrombolytic agents actively reduce the size of the clot.
Most thrombolytic agents work by activating the enzyme plasminogen, which clears the cross-linked fibrin
mesh (the backbone of a clot). This makes the clot soluble and subject to further proteolysis
by other enzymes, and restores blood flow over occluded blood vessel
s.
Apart from streptokinase, all thrombolytic drugs are administered together with heparin
(unfractionated or low molecular weight heparin
), usually for 24–48 hours.
Thrombolysis is usually intravenous. It may also be used during an angiogram
(intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours.
In some settings such as the United States of America, emergency medical technician
s 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
. Emergency Care Practitioners exist, in among other countries, in South Africa
, United Kingdom
, and New Zealand
. Prehospital thrombolysis is always the result of a risk benefit calculation of the heart attack, thrombolysis risks, and PPCI availability. As such, the prehospital practitioner will often consult with the receiving cardiologist as to treatment decisions─ many cardiologists have personal preferences to available treatment options.
Thrombosis
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 and fibrin to form a blood clot to prevent blood loss...
by pharmacological
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
means. It is colloquially referred to as clot busting for this reason. It works by stimulating fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
by plasmin
Plasmin
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
through infusion of analogs of tissue plasminogen activator
Tissue plasminogen activator
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...
(tPA), the protein that normally activates plasmin.
Agents
Thrombolysis suggests the use of thrombolytic drugThrombolytic drug
Thrombolytic drugs are used in medicine to dissolve blood clots in a procedure termed thrombolysis. They limit the damage caused by the blockage of the blood vessel.-Uses:...
s, which are either derived from Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
species, or, more recently, using recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
biotechnology whereby tPA is manufactured by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, resulting in a recombinant tissue plasminogen activator or rtPA.
Some commonly used thrombolytics are:
- streptokinaseStreptokinaseStreptokinase , a protein secreted by several species of streptococci can bind and activate human plasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction and pulmonary embolism...
- urokinaseUrokinaseUrokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...
- Recombinant tissue plasminogen activators
- alteplase (rtPA)
- reteplaseReteplaseReteplase is a thrombolytic drug, used to treat heart attacks by breaking up the clots that cause them....
- tenecteplaseTenecteplaseTenecteplase is an enzyme used as a thrombolytic drug.Tenecteplase is a tissue plasminogen activator produced by recombinant DNA technology using an established mammalian cell line...
Principles
Formation of blood clots lies at the basis of a number of serious diseases (see below). By breaking down the clot, the disease process can be arrested, or the complications reduced. While other anticoagulantAnticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s (such as heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
) decrease the "growth" of a clot, thrombolytic agents actively reduce the size of the clot.
Most thrombolytic agents work by activating the enzyme plasminogen, which clears the cross-linked fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
mesh (the backbone of a clot). This makes the clot soluble and subject to further proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
by other enzymes, and restores blood flow over occluded blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s.
Uses
Diseases where thrombolysis is used:- Myocardial infarctionMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
- StrokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
(ischemic stroke) - Massive pulmonary embolismPulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
- Acute limb ischaemiaAcute limb ischaemiaAcute limb ischaemia occurs when there is a lack of blood flow to a limb. It is usually due to either an embolism or thrombosis of an artery in those with underlying peripheral vascular disease. It is estimated to occur at a rate of 14 per 100,000 per year in the United States...
Apart from streptokinase, all thrombolytic drugs are administered together with heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
(unfractionated or low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
), usually for 24–48 hours.
Thrombolysis is usually intravenous. It may also be used during an angiogram
Angiogram
Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers...
(intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours.
In some settings such as the United States of America, emergency medical technician
Emergency medical technician
Emergency Medical Technician or Ambulance Technician are terms used in some countries to denote a healthcare provider of emergency medical services...
s 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
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
) may be initiated by the emergency care practitioner
Emergency Care Practitioner
An Emergency Care Practitioner may come from either a paramedic, nursing or allied health professional background and most have additional academic qualifications, usually at university, with enhanced skills in medical assessment and extra clinical skills over and above those of a standard...
. Emergency Care Practitioners exist, in among other countries, in South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
, United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, and New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...
. Prehospital thrombolysis is always the result of a risk benefit calculation of the heart attack, thrombolysis risks, and PPCI availability. As such, the prehospital practitioner will often consult with the receiving cardiologist as to treatment decisions─ many cardiologists have personal preferences to available treatment options.