DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

which results from two factors: 1) the lysis of fibrin in
hemostatic plugs at sites of vascular injury, and 2) the
systemic lytic state that results from systemic plasmin
generation, which produces fibrinogenolysis and degradation
of other coagulation factors (especially factors V
and VIII).
The contraindications to fibrinolytic therapy are
listed in Table 30–3. Patients with these conditions
should not receive such treatment.
If heparin is used concurrently with t-PA, serious hemorrhage
will occur in 2-4% of patients. Intracranial hemorrhage is by far the
most serious problem. Hemorrhagic stroke occurs with all regimens
and is more common when heparin is used. In several large studies,
t-PA was associated with an excess of hemorrhagic strokes of about
0.3% of treated patients. Based on the data of three large trials
involving almost 100,000 patients, the efficacies of t-PA and streptokinase
in treating myocardial infarction are essentially identical.
Both agents reduce death and reinfarction by ~30% in regimens containing
aspirin. With good evidence that primary coronary angioplasty
with or without stent placement, when feasible, is superior to
thrombolytic therapy, the use of fibrinolytic therapy has decreased.
Fibrinolytic therapy remains the treatment of choice for patients with
acute ischemic stroke who present within 3 hours of symptom onset.
Inhibitors of Fibrinolysis
Aminocaproic Acid. Aminocaproic acid (AMICAR,
generic) is a lysine analog that competes for lysine
binding sites on plasminogen and plasmin, blocking the
interaction of plasmin with fibrin. Aminocaproic acid
is thereby a potent inhibitor of fibrinolysis and can
reverse states that are associated with excessive fibrinolysis.
The main problem with its use is that thrombi
that form during treatment with the drug are not lysed.
For example, in patients with hematuria, ureteral
obstruction by clots may lead to renal failure after treatment
with aminocaproic acid. Aminocaproic acid has
been used to reduce bleeding after prostatic surgery or
after tooth extractions in hemophiliacs. Use of
aminocaproic acid to treat a variety of other bleeding
disorders has been unsuccessful, either because of limited
benefit or because of thrombosis (e.g., after subarachnoid
hemorrhage).
Aminocaproic acid is absorbed rapidly after oral administration,
and 50% is excreted unchanged in the urine within 12 hours. For
intravenous use, a loading dose of 4-5 g is given over 1 hour, followed
by an infusion of 1-1.25 g/hour until bleeding is controlled. No more
than 30 g should be given in a 24-hour period. Rarely, the drug causes
myopathy and muscle necrosis.
Tranexamic Acid. Tranexamic acid (CYKLOKAPRON,
LYSTEDA) is a lysine analog that, like aminocaproic
acid, competes for lysine binding sites on plasminogen
and plasmin, thus blocking their interaction with
fibrin. Tranexamic acid can be used for the same
Table 30–3
Absolute and Relative Contraindications to Fibrinolytic Therapy
Absolute Contraindications
• Prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within 3 months
• Suspected aortic dissection
• Active bleeding or bleeding diathesis (excluding menses)
• Significant closed-head trauma or facial trauma within 3 months
Relative Contraindications
• Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)
• Traumatic or prolonged CPR or major surgery within 3 weeks
• Recent (within 2-4 weeks) internal bleeding
• Noncompressible vascular punctures
• For streptokinase: prior exposure (more than 5 days ago) or prior allergic reaction to streptokinase
• Pregnancy
• Active peptic ulcer
• Current use of warfarin and INR >1.7
CPR, cardiopulmonary resuscitation; INR, international normalized ratio.