Heparin - Drug Monograph

Introduction

Heparin is a naturally occurring glycosaminoglycan anticoagulant that has been used clinically since the 1930s. It remains one of the most widely prescribed anticoagulants worldwide for the prevention and treatment of thromboembolic disorders. Unlike oral anticoagulants, heparin requires parenteral administration and produces an immediate anticoagulant effect, making it particularly valuable in acute care settings.

Mechanism of Action

Heparin exerts its anticoagulant effect by binding to antithrombin III (AT III), a natural anticoagulant protein. This binding causes a conformational change in AT III that dramatically accelerates its ability to inactivate several coagulation factors, primarily thrombin (Factor IIa) and Factor Xa. Heparin also inactivates Factors IXa, XIa, and XIIa to a lesser extent. The heparin-AT III complex is approximately 1000 times more effective than AT III alone in inhibiting these coagulation factors.

Indications

• Treatment and prophylaxis of venous thromboembolism (deep vein thrombosis and pulmonary embolism)
• Prevention of clotting in arterial and cardiac surgery
• Prophylaxis of thromboembolism in patients with atrial fibrillation
• Treatment of acute coronary syndromes (unstable angina, non-ST elevation myocardial infarction)
• Prevention of clotting during extracorporeal circulation (hemodialysis, cardiopulmonary bypass)
• Maintenance of patency in intravenous catheters

Dosage and Administration

• Initial bolus: 80 units/kg followed by continuous infusion of 18 units/kg/hour
• Adjust based on activated partial thromboplastin time (aPTT) monitoring

• Prophylaxis: 5,000 units every 8-12 hours
• Treatment: Initial dose of 333 units/kg followed by 250 units/kg every 12 hours

• Renal impairment: Use with caution; monitor aPTT closely
• Hepatic impairment: Use with caution; may have altered response
• Obesity: Dosing based on total body weight
• Pediatrics: Dosing varies by age and indication

Pharmacokinetics

Contraindications

• Active bleeding or high risk of bleeding
• History of heparin-induced thrombocytopenia (HIT)
• Severe thrombocytopenia
• Hypersensitivity to heparin or pork products
• Uncontrolled hypertension
• Recent brain, spinal, or eye surgery
• Suspected intracranial hemorrhage

Warnings and Precautions

• Risk of hemorrhage: Monitor for signs of bleeding
• Heparin-induced thrombocytopenia: Monitor platelet counts
• Hyperkalemia: May occur due to aldosterone suppression
• Osteoporosis: With long-term use (>3 months)
• Rebound hypercoagulability: May occur after discontinuation

Drug Interactions

• Oral anticoagulants (warfarin): Increased risk of bleeding
• Antiplatelet agents (aspirin, clopidogrel): Additive anticoagulant effect
• Thrombolytics (tPA, streptokinase): Increased bleeding risk
• NSAIDs: Increased bleeding risk
• Digoxin, nicotine, tetracycline: May decrease anticoagulant effect
• Antihistamines, digitalis, tetracyclines: May partially counteract heparin

Adverse Effects

• Injection site reactions (pain, erythema, bruising)
• Mild bleeding (epistaxis, gingival bleeding)

• Major hemorrhage (GI bleeding, intracranial hemorrhage)
• Heparin-induced thrombocytopenia (HIT)
• Anaphylactic reactions
• Osteoporosis (with long-term use)
• Skin necrosis
• Hyperkalemia
• Alopecia

Monitoring Parameters

• aPTT: Target 1.5-2.5 times control (typically 60-80 seconds)
• Complete blood count: Baseline and every 2-3 days (monitor for HIT)
• Hemoglobin/hematocrit: Monitor for occult bleeding
• Serum creatinine: Assess renal function
• Potassium: Monitor for hyperkalemia
• Signs of bleeding: Clinical assessment regularly
• Anti-Xa levels: Alternative monitoring method, especially in pregnancy

Patient Education

• Report any signs of bleeding (unusual bruising, blood in urine/stool, bleeding gums)
• Use soft-bristle toothbrush and electric razor to minimize bleeding risk
• Avoid NSAIDs and aspirin unless specifically approved by healthcare provider
• Inform all healthcare providers about heparin therapy before any procedures
• Report any signs of allergic reaction (rash, itching, swelling, difficulty breathing)
• Be aware of symptoms of blood clots (swelling, pain, redness in limbs)
• Notify provider immediately if experiencing severe headache, weakness, or confusion

References

1. Hirsh J, Anand SS, Halperin JL, et al. Guide to anticoagulant therapy: Heparin. Circulation. 2001;103(24):2994-3018. 2. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S-e43S. 3. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e495S-e530S. 4. FDA Prescribing Information: Heparin Sodium Injection. 2020. 5. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359. 6. Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):7S-47S.