Jessica L. Smith
ANTITHROMBOTIC AGENTS
ORAL ANTICOAGULANTS
Oral anticoagulants inhibit acute thrombus formation and propagation, and also reduce the risk of embolism from an existing thrombus.
Warfarin inhibits synthesis of vitamin K–dependent clotting factors and antithrombotic proteins C and S. Dosing is guided by the international normalized ratio (INR), which is derived from the prothrombin time (PT).
The therapeutic range of INR is between 2 and 3. Mechanical heart valves require an INR of 2.5 to 3.5.
Drug interactions, certain foods, and certain disease states interfere with warfarin absorption or metabolism, which may be clinically significant.
Warfarin is contraindicated in pregnancy secondary to teratogenicity.
Full anticoagulation occurs about 3 to 4 days after initiating therapy.
During the first 24 to 3 6 hours, a transient hypercoagu-lable state occurs; therefore, a parenteral anticoagulant should be used until an adequate INR is achieved for 2 days.
Dabigatran is the only available oral direct thrombin inhibitor in the United States. It requires no monitoring, no reversal agent is available, and long-term safety has not been established.
PARENTERAL ANTICOAGULANTS
Unfractionated heparin (UFH) inhibits multiple steps in the coagulation cascade.
An IV bolus of 60 to 80 U/kg is followed by IV infusion at 12 to 18 U/kg/h.
Dosing is guided by the partial thromboplastin time (PTT); the desired therapeutic range is 1.5 to 2.5 times the normal value.
Low-molecular-weight heparins (LMWH) (enoxaparin, dalteparin, and ardeparin) are derivatives of heparin.
Advantages of LMWH over UFH include longer half-life and decreased binding to plasma proteins, endothelial cells, and macrophages.
LMWH is a much more predictable anticoagulant with fixed dose-response relationships. LMWH (eg, lovenox 1 milligram/kg every 12 hours) can be administered subcutaneously (SC) once to twice daily, and does not require monitoring, except in patients with renal failure and obesity.
LMWH may be used safely in pregnancy.
UFH or LMWH is indicated for deep venous thrombosis (DVT) prophylaxis and treatment, pulmonary embolism (PE), unstable angina, and acute myocardial infarction (AMI).
Only enoxaparin is approved for outpatient management of DVT.
DIRECT THROMBIN INHIBITORS (BIVALIRUDIN, LE PI RU DIN, ARGATROBAN)
Hirudin, a protein derived from leeches, is now prepared using recombinant technology.
Hirudin and its analogues inhibit both circulating and clot-bound thrombin.
These are currently approved for use in patients with heparin-induced thrombocytopenia and as anticoagulants during percutaneous coronary intervention.
ANTIPLATELET AGENTS
Aspirin is an irreversible inhibitor of cyclooxygenase, an enzyme that inhibits platelet aggregation.
The recommended antiplatelet dose is usually 81 to 162 milligrams daily.
Side effects of aspirin are usually gastrointestinal (GI); active GI bleeding is a contraindication. Patients with guaiac-positive stool and no active bleeding can be treated and carefully monitored.
Nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit cyclooxygenase; platelet inhibition usually lasts less than 24 hours.
Ticlopidine 250 milligrams PO twice daily and clopidogrel 75 milligrams PO daily inhibit platelet aggregation.
These agents should be used for acute coronary syndromes in patients who cannot take aspirin.
Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) inhibit platelet aggregation, prevent thrombosis, and may augment fibrinolysis.
These agents can improve outcomes in select patients with unstable angina and non–ST elevation MI; they should be used in consultation with an interventional cardiologist.
FIBRINOLYTIC AGENTS
Fibrinolytic agents convert plasminogen to plasmin, which dissolves the fibrin in a thrombus.
Streptokinase (SK) and anistreplase (APSAC) are anti-genic, and treatment should not occur within 6 months of prior therapy, or 12 months of streptococcal infection.
Tissue plasminogen activator (tPA) is theoretically more “clot specific” than SK or APSAC.
Reteplase and tenecteplase are modified tPA, designed to improve efficacy and safety.
Although the side effect profiles of fibrinolytics are similar, bolus-dosing (APSAC, reteplase, and tenecteplase) results in significantly fewer medication errors.
INDICATIONS FOR ANTITHROMBOTIC THERAPY
ACUTE MYOCARDIAL INFARCTION
If angioplasty within 90 minutes of arrival to the emergency department is unavailable, fibrinolytic therapy should be initiated within 30 minutes. In the absence of contraindications (Table 140-1), use fibrinolytics if the patient is within 12 hours of symptom onset, and has either ST-segment elevation in two or more contiguous leads or new-onset left bundle-branch block.
Angioplasty is preferred in patients with cardiogenic shock.
Timely initiation of therapy is more important than the specific agent utilized.
Aspirin should be administered immediately. In patients with aspirin allergy, clopidogrel or ticlopidine should be used instead.
TABLE 140-1 General Contraindications to Fibrinolytic Therapy
PULMONARY EMBOLISM OR DEEP VENOUS THROMBOSIS
Treatment of PE or DVT can be initiated with either UFH or LMWH.
LMWH is as effective as UFH, with fewer side effects, and allows for outpatient management of select patients.
Select patients may benefit from fibrinolytic therapy.
ISCHEMIC STROKE
tPA may benefit select stroke patients if administered within 3 hours of symptom onset; there is an increased risk of conversion to hemorrhagic stroke.
Fibrinolytic agents should not be given to patients with uncontrolled hypertension, signs of hemorrhagic stroke, rapidly improving symptoms, or patients with contraindications.
COMPLICATIONS OF ANTICOAGULATION AND ANTITHROMBOTIC THERAPY
Emergency treatments of bleeding complications of antithrombotic therapy are listed in Table 140-2.
TABLE 140-2 Emergency Trseatment of Bleeding Complications of Antithrombotic Therapy
For further reading in Tintinalli’S Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 234, “Anticoagulants, Antiplatelet Agents, and Fibrinolytics,” by David E. Slattery and Charles V. Pollack, Jr.