AlteplasePA study guide

Mechanism

Recombinant tissue plasminogen activator (tPA), a serine protease. Bound to thrombus fibrin, it converts clot-trapped plasminogen to plasmin, producing local fibrinolysis with limited systemic proteolysis. Circulating fibrinogen falls 16% to 36% after a 100 mg dose. Cleared rapidly, mainly by the liver; initial half-life under 5 minutes.

Sources: [1][2][3][4]

Why they happen and how to manage them

Bleeding and intracranial hemorrhage

Plasmin lyses fibrin in hemostatic plugs as well as in the target clot, and systemic fibrinogen falls. Management: Stop the infusion. With sudden neurologic change, headache, nausea, or vomiting, stop and get emergent head imaging; replace fibrinogen and give antifibrinolytics per protocol.

Angioedema

Plasmin increases bradykinin formation, and ACE inhibitors block bradykinin breakdown. Management: Stop the infusion; give antihistamines, IV corticosteroids, or epinephrine; protect the airway.

Embolization

Partial lysis of a left heart thrombus or of residual deep vein clot releases fragments. Management: Weigh risk in mitral stenosis or atrial fibrillation; follow PE lysis with anticoagulation.

Cholesterol embolization

Lysis of fibrin over atheromatous plaque can release cholesterol crystals, especially after catheter procedures. Management: Supportive care; watch the toes, skin, and renal function.

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Common and serious

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Narrow therapeutic index

The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.

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aPTT (partial thromboplastin time)

Why

Pretreatment coagulation check for stroke; timing anticoagulation after PE lysis

When

Before stroke treatment in patients recently on heparin; near the end of the PE infusion. Results may be unreliable while alteplase is in the sample

Act on

Discontinue for an elevated pretreatment aPTT in stroke; after PE, start anticoagulation once the PTT is twice normal or less

Normal

25 to 35 seconds when not on a blood thinner.

Sources: [1][2][3][4]

Blood pressure

Why

Bleeding risk, especially intracranial hemorrhage

When

Frequently during and after stroke treatment

Act on

Severe uncontrolled hypertension is a contraindication; weigh risk above 175/110 mm Hg

Normal

Below 120/80 mm Hg.

Sources: [1][2][3][4]

INR (prothrombin time)

Why

Pretreatment coagulation check for stroke

When

Before stroke treatment in patients recently on oral anticoagulants; otherwise treatment can start before results return

Act on

Discontinue if the pretreatment INR is above 1.7

Normal

INR 0.8 to 1.1 when not on a blood thinner. On warfarin, the usual target is 2.0 to 3.0.

Sources: [1][2]

Adult dose

Acute ischemic stroke

0.9 mg/kg, maximum 90 mg total: 10% as an IV bolus over 1 minute, the rest infused over 60 minutes. Start within 3 hours of symptom onset.

AMI, accelerated infusion

Over 67 kg: 15 mg IV bolus, 50 mg over the first 30 minutes, then 35 mg over the next 60 minutes. 67 kg or less: 15 mg bolus, 0.75 mg/kg over 30 minutes, then 0.50 mg/kg over 60 minutes. Studied only with heparin and aspirin.

AMI, 3-hour infusion

65 kg or more: 100 mg total, 60 mg in the first hour (6 to 10 mg of it as a bolus), 20 mg in the second hour, 20 mg in the third. Under 65 kg: 1.25 mg/kg over 3 hours. Never exceed 100 mg for AMI; 150 mg or more raised intracranial bleeding.

Acute massive pulmonary embolism

100 mg by IV infusion over 2 hours. Start parenteral anticoagulation near the end of or right after the infusion, once the PTT or thrombin time is twice normal or less.

Sources: [1][2][3][4]

Renal adjustment

No renal dose adjustment on the label. Hemostatic defects from severe renal disease raise bleeding risk, and cholesterol embolization can present as acute renal failure.

Sources: [1][2]

Hepatic adjustment

No hepatic dose adjustment on the label. Clearance is mainly hepatic, and significant hepatic dysfunction or hemostatic defects from severe liver disease raise bleeding risk.

Sources: [1][2]

Boxed warning

None on the current label. Bleeding, including intracranial hemorrhage, is the leading labeled warning.

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Contraindications

• Active internal bleeding
• Intracranial or intraspinal surgery or serious head trauma within the past 3 months
• Intracranial conditions that raise bleeding risk, such as some neoplasms, arteriovenous malformations, or aneurysms
• Bleeding diathesis
• Current severe uncontrolled hypertension
• Stroke treatment: current intracranial hemorrhage or subarachnoid hemorrhage
• AMI or PE treatment: history of recent stroke

Sources: [1][2][3]

Key interactions

Anticoagulants (heparin, warfarin) and antiplatelet drugs (aspirin)

Raise bleeding risk when given before, during, or after alteplase. Heparin and aspirin during the first 24 hours after stroke treatment have not been studied.

ACE inhibitors

Higher risk of angioedema, reported mainly in stroke patients.

Other medications in the same infusion

Do not add any other drug to an alteplase infusion solution.

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Antidote or reversal

No specific reversal agent on the label. For serious bleeding, stop the infusion and treat appropriately. For hypersensitivity or angioedema, stop the infusion and give antihistamines, IV corticosteroids, or epinephrine.

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Pregnancy

Human data are too limited to define a drug-associated risk. Alteplase was embryocidal in rabbits at exposures near the AMI dose. Bleeding is the most common complication of thrombolysis, and pregnancy may raise that risk.

Sources: [1][2]

Lactation

No data on alteplase in human milk, effects on the breastfed infant, or milk production.

Sources: [1]

Pediatric

Safety and effectiveness in children have not been established.

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Geriatric

In stroke trials, age over 77 was among factors linked to more intracranial hemorrhage, though outcomes still favored treatment. In AMI, patients over 75 had a 4.0% stroke rate with accelerated alteplase. Advanced age raises bleeding risk.

Sources: [1][2]