Tissue plasminogen activator (tPA) is classified as a serine protease (enzymes that cleave peptide bonds in proteins). It is thus one of the essential components of the dissolution of blood clots. Its primary function includes catalyzing the conversion of plasminogen to plasmin, the primary enzyme involved in dissolving blood clots.
Recombinant biotechnology has allowed tPA to be manufactured in labs, and these synthetic products are called recombinant tissue plasminogen activator (rtPA). Examples of these drugs include alteplase, reteplase, and tenecteplase. These drugs have undergone various modifications to amplify their pharmacokinetic and pharmacodynamic properties, especially to prolong their short half-life in the circulation and further increase their fibrin specificity, to prevent an unwanted fibrinolytic state.
Indications for the use of tPA include the following:
tPA is a thrombolytic (i.e., it breaks up blood clots) formed by aggregation of activated platelets into fibrin meshes by activating plasminogen. More specifically, it cleaves the zymogen plasminogen at its Arg561-Val562 peptide bond to form the serine protease, plasmin. Plasmin, an endogenous fibrinolytic enzyme, breaks the cross-links between fibrin molecules, which are the structural support of the blood clot, and its activity is extremely short-lived. This short duration is because alpha 2-antiplasmin, an abundant inhibitor of plasmin, quickly inactivates it and restricts the action of plasmin to the vicinity of the clot.
The following sequence summarizes the action of tPA:
Plasminogen activator inhibitor 1 (PAI 1) eventually terminates the catalytic activity of tPA by binding to it, and this inactive complex (PAI 1-bound tPA) is removed from the circulation by the liver, more specifically via the scavenger receptor, LDL receptor-related protein 1 (LRRP1). In the nervous system, a neuronal-specific inhibitor of tPA, neuroserpin, acts similarly to PAI 1, and the LRRP1 internalizes the inactive tPA-neuroserpin complexes for removal from circulation.
Alteplase administration is via the intravenous route. However, for catheter clearance, it is administered directly into the catheter.
Acute myocardial infarction
For the management of acute myocardial infarction in adults, administer alteplase as soon as possible after the onset of symptoms. The patient's weight determines the dose to be administered, which is not to exceed 100 mg irrespective of the selected administration method (accelerated infusion preferred by the AHA/ACCA or slower, 3-hour infusion as per manufacturer's labeling).
Accelerated infusion (1-1/2 hr):
Acute ischemic stroke
Dosing considerations for acute ischemic stroke:
Arterial thrombosis and embolism
Central venous catheter occlusion
After 30 minutes of dwell time, assess the function of the catheter by attempting to aspirate blood; if one cannot aspirate blood 120 minutes after dwell time, a second dose may be administered, and repeat the process.
If there is a restoration of catheter function, aspirate around 4 to 5 mL of blood in patients who weigh 10 kg or more (aspirate around 3 mL if the patient weighs less than 10 kg) to remove the drug and the residual clot. Then gently irrigate with 0.9% NaCl.
Pleural Catheter or Chest tube drainage
Alteplase: Adverse effects occur in 1% to 10% of the people who receive alteplase. The most common adverse effect is bleeding, and the most serious is a stroke. Other side effects include bruising, pulmonary edema, arterial embolism, deep vein thrombosis, orolingual angioedema, intracranial hemorrhage, shock, hypersensitivity, nausea/vomiting, seizure, ischemic stroke, thromboembolism, and sepsis.
Tenecteplase: Adverse effects occur in greater than 10% of the patients who receive tenecteplase. The most common is minor bleeding. Other adverse effects include fever, myocardial infarction, reperfusion arrhythmias, nausea/vomiting, edema, allergic reaction, and cholesterol embolization.
Reteplase: As with other tPAs, the most common adverse effect seen with reteplase is bleeding. Other observed adverse effects include reperfusion arrhythmias, hypotension, nausea/vomiting, cardiogenic shock, muscle pain, allergic reaction, a reaction at the injection site, anemia, gastrointestinal/urogenital bleed, intracranial hemorrhage, cholesterol embolization.
2. Do not administer tPA in the management of acute myocardial infarction or pulmonary embolism in the following:
Monitoring During Therapy With tPA
Monitoring After Therapy With tPA
The drug used to reverse tPA toxicity is aminocaproic acid, an FDA-approved drug for the management of acute bleeding caused by increased fibrinolytic activity. It acts as an effective inhibitor for proteolytic enzymes like plasmin, which is the primary enzyme responsible for fibrinolysis.
Monitor closely with any drug that causes anticoagulation as there is an increased risk of bleeding.
tPA has a significant risk of causing complications as well as helping the patient. An interprofessional team consisting of the nurses, pharmacists, and clinicians exercising open lines of communication should monitor patients receiving this drug to provide the safest care and best patient outcome. [Level V]
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