tissue plasminogen activator


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Related to tissue plasminogen activator: streptokinase

activator

 [ak´tĭ-va″ter]
a substance that makes another substance active or reactive, induces a chemical reaction, or combines with an enzyme to increase its catalytic activity.
plasminogen activator a substance that activates plasminogen and converts it into plasmin; see t-plasminogen activator and u-plasminogen activator.
tissue plasminogen activator (TPA, t-PA) (t-plasminogen activator) a serine endopeptidase synthesized by endothelial cells, the major physiologic activator of plasminogen; when bound to fibrin clots it catalyzes the conversion of plasminogen to plasmin by hydrolysis of a specific arginine-valine bond. It can be produced by recombinant technology for use in thrombolytic therapy. It acts directly on blood clots and therefore presents a small risk of systemic bleeding; occasionally allergic reactions may occur.
u-plasminogen activator (urinary plasminogen activator) a serine endopeptidase that acts as a plasminogen activator by catalyzing the preferential cleavage of plasminogen at the same arginine-valine bond where t-plasminogen activator cleaves. It is produced in the kidney and excreted in the urine and is used in thrombolytic therapy (when used as a pharmaceutical, it is usually called urokinase). Unlike t-plasminogen activator or prourokinase, it does not require fibrin for activity. Called also urokinase.

alteplase (tissue plasminogen activator, recombinant)

Actilyse (UK), Activase, Activase rt-PA (CA), Cathflo Activase

Pharmacologic class: Plasminogen activator

Therapeutic class: Thrombolytic

Pregnancy risk category C

Action

Converts plasminogen to plasmin, which in turn breaks down fibrin and fibrinogen, thereby dissolving thrombus

Availability

Injection: 2-mg single-patient vials; 50-mg, 100-mg vials

Indications and dosages

Lysis of thrombi obstructing coronary arteries in acute myocardial infarction (MI)

3-hour infusion-

Adults: 100 mg I.V. over 3 hours as follows: 60 mg over first hour (give 6 to 10 mg as bolus over first 1 to 2 minutes), then 20 mg I.V. over second hour, then 20 mg I.V. over third hour

Adults weighing less than 65 kg (143 lb): 1.25 mg/kg I.V. in divided doses over 3 hours, not to exceed 100 mg Accelerated infusion-

Adults weighing more than 67 kg (147 lb): Give total dosage of 100 mg as follows: 15 mg I.V. bolus over 1 to 2 minutes, then 50 mg I.V. over next 30 minutes, then 35 mg I.V. over next 60 minutes.

Adults weighing 67 kg (147 lb) or less: 15 mg I.V. bolus over 1 to 2 minutes, followed by 0.75 mg/kg I.V. over next 30 minutes (not to exceed 50 mg), followed by 0.5 mg/kg I.V. over next hour, not to exceed 35 mg

Acute ischemic cerebrovascular accident (CVA)

Adults: 0.9 mg/kg I.V. over 1 hour, to a maximum dosage of 90 mg, with 10% of total dosage given as I.V. bolus within first minute

Acute massive pulmonary embolism

Adults: 100 mg I.V. over 2 hours, followed by heparin

Restoration of function of central venous access device

Adults weighing 30 kg (66 lb) or more:Cathflo Activase-2 mg/2-ml concentration instilled in dysfunctional catheter. If catheter function isn't restored in 120 minutes after first dose, may give second dose.

Adults weighing 10 kg (22 lb) to less than 30 kg:Cathflo Activase-Use 110% of catheter lumen volume not to exceed 2 mg/2-ml concentration instilled in dysfunctional catheter. If catheter function isn't restored in 120 minutes after first dose, may give second dose.

Off-label uses

• Small-vessel occlusion by microthrombi
• Peripheral arterial thromboembolism

Contraindications

• Hypersensitivity to drug or its components (Cathflo Activase)
• Seizures, stroke, aneurysm, intracranial neoplasm, bleeding diathesis

Precautions

Use cautiously in:
• hypersensitivity to anistreplase or streptokinase
• GI or genitourinary bleeding, ophthalmic hemorrhage, organ biopsy, severe hepatic or renal disease
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

Be aware that intracranial hemorrhage must be ruled out before therapy begins.

To treat acute ischemic CVA, give within 3 hours of initial signs or symptoms.

If uncontrolled bleeding occurs, stop infusion and notify prescriber immediately.
• Give I.V. only, using controlled-infusion pump.
• Reconstitute with unpreserved sterile water for injection. May be further diluted with normal saline solution or D5W.

Adverse reactions

CNS: cerebral hemorrhage, cerebral edema, CVA (with accelerated infusion)

CV: hypotension, bradycardia, recurrent ischemia, pericardial effusion, pericarditis, mitral regurgitation, electromechanical dissociation, arrhythmias, cardiogenic shock, heart failure, cardiac arrest, cardiac tamponade, myocardial rupture, embolization, venous thrombosis

GI: nausea, vomiting, GI bleeding

GU: GU tract bleeding

Hematologic: spontaneous bleeding, bone marrow depression

Musculoskeletal: musculoskeletal pain

Respiratory: pulmonary edema

Skin: bruising, flushing

Other: fever, edema, phlebitis or bleeding at I.V. site, hypersensitivity reaction (including rash, anaphylactic reaction, laryngeal edema), sepsis

Interactions

Drug-drug.Aspirin, drugs affecting platelet activity (such as abciximab, heparin, dipyridamole, oral anticoagulants, vitamin K antagonists): increased risk of bleeding

Drug-diagnostic tests.Blood urea nitrogen: elevated level

Patient monitoring

• Monitor vital signs, ECG, and neurologic status.
• Maintain strict bed rest.
• Watch for signs and symptoms of bleeding tendency and hemorrhage.
• Monitor patient on Cathflo Activase for GI bleeding, venous thrombosis, and sepsis.
• Evaluate results of clotting studies.

Patient teaching

• As appropriate, explain therapy and monitoring to patient and family.

tis·sue plas·min·o·gen ac·ti·va·tor (TPA, tPA),

[MIM*173370]
1. a naturally occurring thrombolytic serine protease that catalyzes the conversion of plasminogen to plasmin;
2. a genetically engineered protein used as a thrombolytic agent in myocardial infarction, stroke, and peripheral vascular thrombosis.

TPA is a single-chain glycoprotein with a molecular weight of about 70 kD. Released by endothelial cells at sites of vascular injury, it modulates thrombogenesis by converting fibrin-bound plasminogen to plasmin, cleaving the arginine-valine bond of plasminogen at the 560-561 position. As a result, fibrin strands in a clot are chemically degraded and platelet adhesion and aggregation are inhibited. TPA has little effect on plasminogen in the absence of fibrin, and its release does not significantly reduce systemic concentrations of fibrinogen. Alteplase, a synthetic TPA produced by recombinant DNA technology, improves outcomes when administered intravenously in acute myocardial infarction and in selected cases of stroke, pulmonary embolism, and peripheral ischemia due to thrombosis. It has a circulating half-life of only 4-6 minutes, but persists in clots up to 7 hours. see thrombolytic therapy

tissue plasminogen activator

n. Abbr. tPA or TPA
1. A clot-dissolving enzyme that is produced naturally by cells in the walls of blood vessels and catalyzes the conversion of plasminogen to plasmin.
2. A preparation of this enzyme that is produced by genetic engineering and is used as a drug to dissolve blood clots in the immediate treatment of certain cases of stroke and heart attack.

tissue plasminogen activator (TPA)

a clot-dissolving substance produced naturally by cells in the walls of blood vessels. It is also manufactured synthetically by genetic engineering techniques. TPA activates plasminogen to dissolve clots and has been used therapeutically to open occluded coronary arteries, as well as cerebral arteries.

PLAT

A gene on chromosome 8p12 that encodes tissue plasminogen activator, which converts inactive plasminogen to plasmin by hydrolysing a single Arg-Val bond in plasminogen, thereby playing a key role in tissue remodelling, degradation, cell migration and other cellular events. PLAT directly facilitates neuronal migration.

tissue plasminogen activator

A thrombolytic protease, the natural form of which is the physiologic activator of the fibrinolytic system; TPA is released from vascular endothelium by epinephrine, exertion, adherent thrombi, or vascular compression; tPA is commercially available in a recombinant form, r-tPA; tPA ↓ mortality of MI in the immediate post-ischemic period; thrombolytic therapy given within the first post-MI hr ↓ mortality by 47%, ↓ mortality in PTE. See Thrombolytic therapy.

tis·sue plas·min·o·gen ac·ti·va·tor

(tPA) (tish'ū plaz-min'ŏ-jen ak'ti-vā-tŏr)
Thrombolytic serine protease catalyzing the enzymatic conversion of plasminogen to plasmin; a genetically engineered protein used as a thrombolytic agent in patients with thrombotic occlusion of a coronary or cerebral artery.

tissue plasminogen activator (TPA)

A natural body ENZYME involved in the breakdown of blood clots. TPA is a small molecule protease that activates the conversion of plasminogen to plasmin. Plasmin is an enzyme that can convert fibrin strands in the blood clot to soluble products so that blood clot can be dissolved. TPA has been produced synthetically, as alteplase and is used in the treatment of conditions, such as heart attacks, caused by blockage of arteries by clotted blood.

Tissue plasminogen activator (tPA)

A substance that is sometimes given to patients within three hours of a stroke to dissolve blood clots within the brain.
Mentioned in: Stroke

tissue

a group or layer of similarly specialized cells that together perform certain special functions. For anatomically specific tissues see under their identifying titles, e.g. adipose, connective.

tissue death
tissue density
the penetrability of tissue by x-rays, bone and tooth being most dense, blood and soft tissue the next, fat the next, and gas and air least.
tissue edema
an abnormal accumulation of tissue fluid.
tissue factor
see tissue thromboplastin.
tissue fluid
the extracellular fluid that constitutes the environment of the body cells. It is low in protein, is formed by filtration through the capillaries, and the excess drains away as lymph. See also interstitial fluid.
tissue inhibitors
inhibitors of fibrinolysis; present in placenta.
indifferent tissue
undifferentiated embryonic tissue.
tissue necrosis fever
fever caused by pyrogens released by necrotic pyrogens.
tissue plasminogen activator
see plasminogen activator.
tissue reacting agent
substances that have a poorly defined but advantageous local effect on tissues.
tissue receptor site
a cell receptor common to cells of a particular tissue.
tissue residue
residues of chemical substances that are unacceptable to local pure food legislation especially sulfonamides, estrogens, chlorinated hydrocarbons, heavy metals. These are thought or known to have a deleterious effect on people eating or drinking the relevant animal product. See also chemical food residue.
tissue sensitivity
the susceptibility of individual tissues to injury by x-ray. The injury may be by way of inflammation, necrosis or cessation of cell growth. Fast-growing tissues in which the cells have a high mitotic index are the most sensitive, especially gonads, germinative layer of skin and erythropoietic tissues.
supportive t's
cartilage and bone.
tissue therapy
tissue typing
identification of tissue types for purposes of predicting acceptance or rejection of grafts and organ transplants. The process and purposes of tissue typing are essentially the same as for blood typing. The major difference lies in the kinds of antigens being evaluated. White blood cells, particularly lymphocytes, are used for tissue typing. The acceptance of allografts depends particularly on the matching of MHC antigens. If the donor and recipient are not MHC identical, the allograft is rejected. See also typing.
References in periodicals archive ?
Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.
Qiu et al (22) and Lee and Im (29) have also produced tissue plasminogen activators and measured their activities.
Subcapsular hepatic and intraperitoneal bleed after administration of tissue plasminogen activator in a patient with acute myocardial infarction.
Cyclic AMP potentiates phorbol ester stimulation of tissue plasminogen activator release and inhibits secretion of plasminogen activator inhibitor-1 from human endothelial cells.
Currently, tissue plasminogen activator (t-PA) (Alteplase[R], Cathflo Activase[R]) is the only thrombolytic agent approved by the FDA for the purpose of restoring function and patency in CVADs (Genetech, Inc.
Tissue plasminogen activator (tPA) can dissolve blood clots that cause most heart attacks and strokes (ischemic).
Subsequently, in 2001, alteplase (CathFlowJ Activase7, Genentech, South San Francisco), a recombinant version of the naturally occurring tissue plasminogen activator molecule, was licensed for clearance of thrombosed catheters.
Recent studies have shown that a clot-dissolving medication, tissue plasminogen activator (t-PA), is highly effective in reversing the effects of the most common forms of strokes when administered within three hours of early symptoms.
Similarly, in a cost-effective analysis of thrombolytic therapy with tissue plasminogen activator (t-PA) compared to streptokinase, the authors conclude, "The cost-effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.
The human body's fibrinolytic, clot dissolving, system utilises two natural enzymes, tissue plasminogen activator (tPA) and prourokinase (proUK), rather than only one of them.