Tissue plasminogen activator (tPA) is considered for the treatment of a patient who arrives in the emergency department following the onset of symptoms of myocardial infarction. Which of the following is a contraindication for treatment with t-PA?
A. Worsening chest pain that began earlier in the evening.
B. History of cerebral hemorrhage.
C. History of prior myocardial infarction.
D. Hypertension.
Correct Answer: B. History of cerebral hemorrhage.
A history of cerebral hemorrhage is a contraindication to tPA because it may increase the risk of bleeding. Bleeding associated with alteplase therapy can be divided into two broad categories. Internal bleeding includes intracranial bleeding (0.4% to 15.4%), retroperitoneal bleeding (less than 1%), gastrointestinal (GI) bleeding (5%), genitourinary bleeding (4%), and respiratory bleeding. Superficial or surface bleeding is observed mainly at invaded or disturbed sites such as venous cutdowns, arterial punctures, and recent surgical intervention sites.
Option A: TPA acts by dissolving the clot blocking the coronary artery and works best when administered within 6 hours of onset of symptoms. Alteplase acts within the endogenous fibrinolytic cascade to convert plasminogen to plasmin by hydrolyzing the arginine-valine bond in plasminogen. The activated plasmin then degrades fibrin and fibrinogen, allowing for the dissolution of the clot and re-establishment of blood flow.
Option C: Prior MI is not a contraindication to tPA. FDA-approved indications for alteplase include pulmonary embolism, myocardial infarction with ST-segment elevation (STEMI), ischemic stroke when given within 3 hours of the start of symptoms, and re-establishment of patency in occluded intravenous (IV) catheters.
Option D: Patients receiving tPA should be observed for changes in blood pressure, as tPA may cause hypotension. There are no therapeutic drug monitoring recommendations that pertain to the efficacy of tPA therapy. If prolonged off-label therapy is occurring in the event of catheter-directed treatment or repeated dosing in valve thrombosis, serial imaging of the thrombus is reasonable. The safety profile is best monitored by prothrombin time (PT), partial thromboplastin time (PTT), Hemoglobin, and hematocrit to assess ongoing bleeding.