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Thrombolysis, also called fibrinolytic therapy, is the breakdown (
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
) of
blood clots A thrombus (plural thrombi), 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 cr ...
formed in blood vessels, using medication. It is used in ST elevation myocardial infarction,
stroke 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 functionin ...
, and in cases of severe venous thromboembolism (massive pulmonary embolism or extensive deep vein thrombosis). 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: * ST elevation myocardial infarction: Large trials have shown that mortality can be reduced using thrombolysis (particularly fibrinolysis) in treating heart attacks. It works by stimulating secondary fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator (tPA), the protein that normally activates plasmin. *
Stroke 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 functionin ...
: Thrombolysis reduces major disability or death when given within 3 hours (or perhaps even 6 hours) of ischaemic stroke onset when there are no contraindications to treatment. * Massive pulmonary embolism. For the treatment of a massive pulmonary embolism, ''catheter-directed therapy'' is a safer and more effective alternative to systemic thrombolysis. This involves the injecting of drugs directly into the clot. * Severe deep vein thrombosis (DVT), such as
phlegmasia cerulea dolens Phlegmasia cerulea dolens (PCD) (literally: 'painful blue inflammation'), not to be confused with preceding phlegmasia alba dolens, is an uncommon severe form of lower extremity deep venous thrombosis (DVT) that obstructs blood outflow from a vei ...
, which threatens limb loss, or iliofemoral DVT, where clots involve at a minimum the common iliac vein * Acute limb ischaemia * Clotted hemothorax Thrombolysis is usually
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
. 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). Thrombolysis is performed by many types of medical specialists, including
interventional radiologist Interventional radiology (IR) is a medical specialty that performs various minimally-invasive procedures using medical imaging guidance, such as x-ray fluoroscopy, computed tomography, magnetic resonance imaging, or ultrasound. IR performs bo ...
s, 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 Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the ...
(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: * Any previous history of
hemorrhagic stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
, ischemic stroke within 3 months. * History of stroke, dementia, or central nervous system damage within 1 year * Head trauma within 3 weeks or brain surgery within 6 months * Known intracranial neoplasm * Suspected aortic dissection * Internal bleeding within 6 weeks * Active bleeding or known bleeding disorder * Traumatic cardiopulmonary resuscitation within 3 weeks Relative contraindications: * Oral anticoagulant therapy * Acute pancreatitis * Pregnancy or within 1 week postpartum * Active peptic ulceration * Transient ischemic attack within 6 months * Dementia * Infective endocarditis * Active cavitating pulmonary tuberculosis * Advanced liver disease * Intracardiac thrombi * Uncontrolled hypertension (systolic blood pressure >180 mm Hg, diastolic blood pressure >110 mm Hg) * Puncture of noncompressible blood vessel within 2 weeks * Previous streptokinase therapy * Major surgery, trauma, or bleeding within 2 weeks


Stroke

Absolute contraindications: * Uncertainty about time of stroke onset (e.g. patients awakening from sleep). * Coma or severe obtundation with fixed eye deviation and complete hemiplegia. * Hypertension: systolic blood pressure ≥ 185mmHg; or diastolic blood pressure >110mmHg on repeated measures prior to study. (if reversed, patient can be treated) * Clinical presentation suggestive of subarachnoid haemorrhage even if the CT scan is normal. * Presumed septic embolus. * Patient having received a heparin medication within the last 48 hours and has an elevated Activated Prothrombin Time (APTT) or has a known hereditary or acquired haemorrhagic diathesis * INR >1.7 * Known advanced liver disease, advanced right heart failure, or anticoagulation, and INR > 1.5 (no need to wait for INR result in the absence of the former three conditions). * Known platelet count <100,000 uL. * Serum glucose is < 2.8 mmol/L or >22.0 mmol/L. Relative contraindications: * Severe neurological impairment with NIHSS score >22. * Age >80 years. * CT evidence of extensive middle cerebral artery (MCA) territory infarction (sulcal effacement or blurring of grey-white junction in greater than 1/3 of MCA territory). * Stroke or serious head trauma within the past three months where the risks of bleeding are considered to outweigh the benefits of therapy. * Major surgery within the last 14 days (consider intra-arterial thrombolysis). * Patient has a known history of intracranial haemorrhage, subarachnoid haemorrhage, known intracranial arteriovenous malformation or previously known intracranial neoplasm * Suspected recent (within 30 days) myocardial infarction. * Recent (within 30 days) biopsy of a parenchymal organ or surgery that, in the opinion of the responsible clinician, would increase the risk of unmanageable (e.g. uncontrolled by local pressure) bleeding. * Recent (within 30 days) trauma with internal injuries or ulcerative wounds. * Gastrointestinal or urinary tract haemorrhage within the last 30 days or any active or recent haemorrhage that, in the opinion of the responsible clinician, would increase the risk of unmanageable (e.g. by local pressure) bleeding. * Arterial puncture at non-compressible site within the last 7 days. * Concomitant serious, advanced or terminal illness or any other condition that, in the opinion of the responsible clinician would pose an unacceptable risk. * Minor or Rapidly improving deficit. * Seizure: If the presenting neurological deficit is deemed due to a seizure. * Pregnancy is not an absolute contraindication. Consider intra-arterial thrombolysis.


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 A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, th ...
, 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: * Streptokinase (Kabikinase) * Urokinase *
Recombinant tissue plasminogen activator Tissue plasminogen activator (abbreviated tPA or PLAT) 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 ...
s (rtPA) ** Alteplase (Activase or Actilyse) **
Reteplase Reteplase, trade names include Retavase, is a thrombolytic drug, used to treat heart attacks by breaking up the clots that cause them. Reteplase is a recombinant non-glycosylated form of human tissue plasminogen activator, which has been modifie ...
(Retavase) **
Tenecteplase Tenecteplase, sold under the trade names TNKase, Metalyse and Elaxim, is an enzyme used as a thrombolytic drug. Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line ...
** Anistreplase (Eminase)


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.


See also

*
TIMI The Thrombolysis In Myocardial Infarction, or TIMI Study Group, is an Academic Research Organization (ARO) affiliated with Brigham and Women's Hospital and Harvard Medical School dedicated to advancing the knowledge and care of patients with car ...
– thrombolysis in myocardial infarction


References

{{Authority control Vascular procedures Neurology procedures