ACUTE MYOCARDIAL INFARCTION: THROMBOLYTIC THERAPY IN THE EMERGENCY DEPARTMENT

Jason R. is a 38-year-old white male who called the ED about 30 min prior so arrival to ask if he should
come to the hospital. Jason said over the phone. "\fy wife's bugging me to come over there. I've got a
heavy pressure in my chest, sort of like indigestion. I've had it before, but it always went away. This time
I can't gel rid of it. "Jason was advised by the ED nurse to come to the hospital, preferably by ambulance.

Jason arrived by car and is noted to look pale and uncomfortable. He complains of pain in the center of
his chest that feels like a heavy pressure that is now going down both arms. The pain has increased in
severity since he left home. Jason rates his pain as 8 on a scale of 1 to 10. Jason is assisted to a stretcher
and while lying in semi-Fowler's position has no dyspnea. His vital signs are temperature 99° F. pulse 60
and regular, respiratory rate 22, and BP 108/60. Lung sounds are clear and heart sounds are regular with
normal s1 and S2. He has an extra heart sound. S4

When questioned about recent health, Jason tells the nurse that he has had chest pain off and on for
about 1 week. Jason describes the pain as a tightness or heaviness in the center of his chest under the
breastbone. Jason also mentions that the pain occurs with physical exertion and goes away with rest.

Jason is married and has two children. He is a sales executive and received a promotion 1 month ago.
Jason smokes about one pack of cigarettes per day. He has no previous medical history and does not
take any drugs. Jason says that his father died of a heart attack and his mother has hypertension.

Triage Assessment, Acuity Level IV: Chest pain, unrelieved: pain continues at rest.

Jason is taken immediately to the treatment area to rule out myocardial ischemia or injury. A 12-lead
ECG is immediately done and reveals ST segment elevation in leads I, II, III, A VF, V4, V5, and V6. T waves
are inverted in VI, V2. and 1 '3. and an abnormal R wave is present in VI. The initial creatinine
phosphokinase (CPK) is reported as 153 (0 to 225 is normal). The ED physician makes a diagnosis of
acute inferior lateral myocardial infarction (MI). True posterior MI is also considered.

Jason is given oxygen via nasal cannula at 5 liters/min and sublingual nitroglycerin with significant
reduction in his pain. After consultation with a cardiologist. Jason is deemed a candidate for
thrombolytic therapy. A lidocaine bolus is administered per protocol and a continuous infusion of
lidocaine is started at 2 mg/min. Tissue plasminogen activator (t-PA) is selected as the thrombolytic
agent for Jason. An intravenous bolus dose of 10 mg of t-PA is given by the physician, and an infusion of
t-PA is initiated at a rate of 50 mg/hr. Jason is then transferred to the coronary care unit (CCU) for
further definitive therapy and monitoring

QUESTIONS

5. What are the effects, side effects, indications, and contraindications of the various thrombolytic
agents currently on the market?

Currently there are three thrombolytic agents available for the treatment of AMI. The thrombolytic
drugs are streptokinase. urokinase. and tissue type plasminogen activator (t-PA) or alteplase. In
addition. there are two investigational drugs in clinical trials: anisoylated plasminogen-streptokinase
activator complex and single-chain urokinase plasminogen activator.
Streptokinase is derived from the streptococcal bacteria. The thrombolytic effect produced by
streptokinase is systemic since the drug combines with circulating plasminogen. Plasmin. the substance
that actually dissolves fibrin clots, is then produced in the circulation. As the plasmin circulates through
the body. a systemic "lytic" state develops. This means that all blood clots will be dissolved and the
patient might develop bleeding problems.

Other problems associated with streptokinase are the prolonged effect on the coagulation system (18 to
24 hr after the drug is given), hypotension associated with administration of the drug. and the possibility
of allergic reactions to this "foreign" substance and of resistance to the drug because of patient
antibodies to streptococcus bacteria (6). Major contraindications to the use of streptokinase are recent
strep infections, recent intracranial or intraspinal surgery or trauma, intra-cranial aneurysm. neoplasm
or arteriovenous malformation, history of cerebrovascular accident (CVA), active internal bleeding,
uncontrolled hypertension, or known bleeding tendency or disorder.

Urokinase is a naturally occurring human enzyme, found in small amounts in urine and produced by
kidney cells. Urokinase converts plasminogen to plasmin in the circulation and produces a systemic lytic
state much the same as the effects of streptokinase. Since uroki-nase is a natural substance, there is less
chance of allergic reactions and hypotension.

Tissue plasminogen activator is a natural substance found in blood cells. It is referred to as a clot-specific
or clot-selective drug since it binds with Fibrin at the site of the newly formed blood clot. This binding
results in the conversion of plasminogen at the site of the clot to plasmin. The effects oft-PA then are
limited to specific fresh blood clots. Side effects are minimal—bleeding from fresh blood clots might
occur. Major contraindications to t-PA are similar to those for other thrombolytic agents. Other possible
contraindications include surgery within the last 10 days, cerebrovascular disease, hypertension,
pregnancy, and any other conditions in which the risk of bleeding is great. Patients must be evaluated
individually on a risk/benefit basis.

The investigational drugs previously mentioned are modified versions of the originals. These drugs, like
t-PA, are designed to be clot-specific and do not result in systemic lytic states.