tissue plasminogen activator

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.

Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.

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.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved

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

Farlex Partner Medical Dictionary © Farlex 2012

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.

The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.

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.

Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved.

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.

McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.

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.

Medical Dictionary for the Health Professions and Nursing © Farlex 2012

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.

Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005

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

Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.