tPA Flashcards
Trade name for tissue plasminogen activator (tPA), alteplase
Activase
Drug classification - tPA
thrombolytic enzyme
How is tPA supplied?
50 and 100 mg vials
Actions (Pharmacodynamics) - tPA
❑ Binds to fibrin in a thrombus and converts entrapped plasminogen to plasmin thus initiating fibrinolysis
❑ Degrades fibrin clots, fibrinogen, and other plasma proteins
Indications - tPA
❑ Management of acute MI through lysis of thrombi obstructing coronary arteries.
❑ Management of acute ischemic stroke through lysis of thrombi obstructing cerebral arteries.
Dosage - tPA for a STEMI
STEMI: Accelerated infusion (1.5 hours) – Give 15 mg IV bolus; then 0.75 mg/kg over the next 30 min (not to exceed 50 mg); then 0.5 mg/kg over 60 min (not to exceed 35 mg); Max total dose or 100mg
Dosage tPA - for an acute ischemic stroke
Acute Ischemic Stroke: Give 0.9 mg/kg (maximum 90 mg) IV, infused over 60 minutes; give 10% of total dose as an initial IV bolus over 1 min; give remaining 90% of total dose IV over next 60 minutes.
Contraindications - tPA
Exclusion Characteristics of Patients With Ischemic Stroke Who Could Be Treated With tPA Within 3 Hours From Symptom Onset:
❑ Head trauma or prior stroke in previous 3 months
❑ Symptoms suggest subarachnoid hemorrhage
❑ Arterial puncture at non-compressible site in previous 7 days
❑ History of previous intracranial hemorrhage
❑ Elevated blood pressure (systolic > 185 mm Hg or diastolic > 110 mm Hg)
❑ Evidence of active bleeding on examination
❑ Acute bleeding diathesis, including but not limited to
▪ Platelet count < 100 000/mm3
▪ Heparin received within 48 hours, resulting in aPTT > upper limit of normal
▪ Current use of anticoagulant with > INR 1.7 or PT 15 seconds
❑ Blood glucose concentration < 2.7 mmol/L
❑ CT demonstrates multilobar infarction (hypodensity > 1/3 cerebral hemisphere)
Contraindications - tPA
Additional Exclusion Characteristics of Patients With Ischemic Stroke Who Could Be Treated With tPA From 3 to 4.5 Hours From Symptom Onset:
❑ Age > 80 years
❑ Severe stroke (NIHSS > 25)
❑ Taking an oral anticoagulant regardless of INR
❑ History of both diabetes and prior ischemic stroke
Contraindications - tPA
For fibrinolytic use in STEMI
❑ Any prior intracranial hemorrhage
❑ Known structural cerebral vascular lesion (e.g., AVM)
❑ Known malignant intracranial neoplasm (primary or metastatic)
❑ Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours
❑ Suspected aortic dissection
❑ Active bleeding or bleeding diathesis (excluding menses)
❑ Significant closed head trauma or facial trauma within 3 months
Precautions - tPA - Ischemic Stroke
Recent experience suggests that under some circumstance with careful consideration and weighing of risk to benefit patients may receive fibrinolytic therapy despite 1 or more relative contraindications. Consider risk to benefit of tPA administration carefully if any of these relative contraindications is present
❑ Only minor or rapidly improving stroke symptoms (clearing spontaneously)
❑ Seizure at onset with postictal residual neurologic impairments
❑ Major surgery or serious trauma within previous 14 days
❑ Recent gastrointestinal or urinary tract hemorrhage (within previous 21days)
❑ Recent acute myocardial infarction (within previous 3 months)
Precautions - tPA - For fibrinolytic use in STEMI
❑ History of chronic, severe, poorly controlled hypertension
❑ Severe uncontrolled hypertension on presentation (SBP > 180 mm Hg or DBP >110 mm Hg) – could be a contraindication in low-risk patients with MI
❑ History of prior ischemic stroke > 3 months, dementia, or known intracranial pathology not covered in contraindications
❑ Traumatic or prolonged (> 10 minutes) CPR or major surgery (< 3 weeks)
❑ Recent (within 2 to 4 weeks) internal bleeding
❑ Non-compressible vascular punctures
❑ For streptokinase / anistreplase: prior exposure (> 5 days ago) or prior allergic reaction to these agents
❑ Pregnancy
❑ Active peptic ulcer
❑ Current use of anticoagulants: the higher the INR, the higher the risk of bleeding
Why should doses over 100mg of tPA be avoided?
Total doses in excess of 100 mg are associated with an increased risk of intracranial bleeding and should be avoided.
What are considerations for tPA
❑ Onset of time of stroke is either witnessed or last known normal
❑ Must be reconstituted with sterile water to 1 mg/ml
❑ Use 2 peripheral IV lines, one exclusively for fibrinolytic administration.
