Tissue-type plasmogen activator - definition of Tissue-type plasmogen activator in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia.

activator /ac·ti·va·tor/ (ak´tĭ-va″ter)

1. a substance that combines with an enzyme to increase its catalytic activity.

2. a substance that stimulates the development of a specific structure in the embryo.

3. a chemical or other form of energy that causes another substance to become reactive or that induces a chemical reaction.

plasminogen activator any of a group of substances that have the ability to cleave plasminogen and convert it into the active form plasmin.

prothrombin activator any one of the substances in the extrinsic or intrinsic pathways of coagulation.

single chain urokinase-type plasminogen activator (scu-PA) prourokinase.

tissue plasminogen activator (TPA) (t-PA), t-plasminogen activator an endopeptidase synthesized by endothelial cells that binds to fibrin clots and catalyzes the cleavage of plasminogen to the active form plasmin. t-PA produced by recombinant technology is used for therapeutic thrombolysis.

u-plasminogen activator formal name for urokinase. Called also urinary plasminogen a.

tissue plasminogen activator

n. Abbr. TPA

1. An enzyme that catalyzes the conversion of plasminogen to plasmin, used to dissolve blood clots rapidly and selectively, especially in the treatment of heart attacks.

2. A preparation of this enzyme that is produced by genetic engineering and used to dissolve clots blocking coronary arteries in heart attack and cranial arteries in certain cases of stroke.

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 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.

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

see necrosis.

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

see glandular 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.

alteplase (tissue plasminogen activator, recombinant) Warning - High-alert drug!

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

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

Off-label uses

• Blocked venous catheter (2-mg bolus injected into catheter for adults and children ages 2 years and older)
• Small-vessel occlusion by microthrombi
• Peripheral arterial thromboembolism

Contraindications

• Active MI or pulmonary embolism in patients with increased bleeding risk
• Previous CVA, history of intracranial hemorrhage, uncontrolled hypertension, seizures, or active internal bleeding

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.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

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

☞ Instruct patient to immediately report adverse reactions, especially unusual bleeding or bruising.
• Stress importance of strict bed rest.
• Tell patient to avoid activities that can cause injury. Advise him to use soft toothbrush and electric razor to avoid gum and skin injury.
• Advise patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.