tissue plasminogen activator

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.

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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

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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.

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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. Cf Thrombolytic therapy.