Oral Anticoagulants
Warfarin (Coumadin):
- Mechanism of Action: Inhibits synthesis of vitamin K-dependent clotting factors X, IX, VII, and II (prothrombin).
Pharmacokinetics:
- Well-absorbed when taken orally.
- Metabolized by CYP 1A2 and 2C9.
- Half-life of 3 to 4 days.
Precautions and Contraindications:
- Pregnancy category X.
- Use cautiously in patients with fall risk, dementia, or uncontrolled hypertension.
- Avoid in hypermetabolic state.
- The major adverse drug reaction is bleeding (Antidote is vitamin K).
- Many drug interactions, including (but not limited to):
- Antiplatelet drugs
- Thrombolytic drugs
- Oral contraceptives, carbamazepine, Vitamin K-containing foods, etc.
Clinical Use and Dosing:
- Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE).
- Start at 5 mg per day (7.5 mg/day if weight greater than 80 kg).
- Consider lower dose in the following situations:
- Older than 75 years
- Multiple comorbid conditions
- Elevated liver enzymes
- Changing thyroid status
- Dose to maintain international normalized ratio (INR) between 2 and 3.
Monitoring:
- INR daily until in therapeutic range for 2 consecutive days.
- Then two or three times weekly for 1 to 2 weeks.
- Then less frequently but at least every 6 weeks.
Rivaroxaban (Xarelto): Factor Xa inhibitor. Apixaban (Eliquis): Factor Xa inhibitor.
- Indications:
- Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation.
- Prophylaxis of DVT following knee replacement surgery.
- Treatment of DVT and PE.
Parenteral Anticoagulants
Heparin:
- Mechanism of Action: Binds with the antithrombin III, inactivating factors IXa, Xa, XIIa, XIII.
Pharmacokinetics:
- Given IV or subcutaneously (SC).
- Extensively protein-bound.
- Metabolized by liver and renally eliminated.
Precautions and Contraindications:
- Pregnancy category C.
- Avoid in advanced hepatic or renal disease.
- Avoid in bleeding disorders or active bleeding.
Adverse Drug Reactions (ADRs):
- May cause thrombocytopenia.
- Life-threatening bleeding.
- Pain at injection site (SC).
- Antidote is protamine sulfate.
Drug Interactions:
- Cephalosporins and penicillins; Warfarin, antiplatelets and thrombolytics; Valproic acid.
Clinical Use and Dosing:
- Given 2 hours pre-operatively.
- Maintenance every 8 to 12 hours for 7 days after surgery.
- Heparin is processed into smaller molecules → low molecular-weight heparins (LMWH).
- Inactivates factor Xa.
Enoxaparin:
- Indications: DVT or PE.
- Given 2 hours before surgery.
Fondaparinux: Selective inhibitor of antithrombin III and factor Xa inhibitor.
- Indications: DVT, hip fracture surgery, or knee replacement.
Dalteparin:
- Indications: Prevention of DVT after abdominal surgery or hip replacement.
Monitoring for Anticoagulants:
- Activated partial thromboplastin time.
- Platelet and hematocrit (Hct) every 2 to 3 days initially.
Patient Education for Anticoagulants:
- Administration: Warfarin dosing may vary day to day.