Heparin Sodium - Drug Monograph

Introduction

Heparin sodium is a naturally occurring glycosaminoglycan anticoagulant that has been used clinically since the 1930s. It remains one of the most widely prescribed parenteral anticoagulants worldwide. Unlike oral anticoagulants, heparin provides immediate anticoagulation effect, making it particularly valuable in acute thrombotic conditions requiring rapid therapeutic intervention.

Mechanism of Action

Heparin exerts its anticoagulant effect by binding to antithrombin III (ATIII), causing a conformational change that accelerates ATIII's ability to inactivate thrombin (factor IIa) and factor Xa. This binding enhances ATIII's inhibitory activity by approximately 1000-fold. Heparin also inactivates factors IXa, XIa, and XIIa. The anticoagulant effect requires the presence of ATIII, and heparin's activity is measured in units rather than mass due to variations in molecular weight and specific activity between preparations.

Indications

• Treatment and prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Prophylaxis of thrombosis in medical and surgical patients
• Treatment of acute coronary syndromes (unstable angina, non-ST-elevation myocardial infarction)
• Anticoagulation during percutaneous coronary interventions
• Prevention of clotting in extracorporeal circulation during cardiac surgery and hemodialysis
• Adjunct therapy in disseminated intravascular coagulation (DIC)

Dosage and Administration

• Initial bolus: 80 units/kg IV, followed by continuous infusion of 18 units/kg/hour
• Alternative: 5000 units IV bolus followed by 1300 units/hour continuous infusion
• Target therapeutic aPTT: 1.5-2.5 times control

• 5000 units SC every 8-12 hours

• 60-70 units/kg IV bolus (maximum 5000 units), followed by 12-15 units/kg/hour infusion

• Renal impairment: Requires careful monitoring; dose adjustment based on aPTT
• Hepatic impairment: Use with caution; may require reduced dosing
• Obesity: Use total body weight for dosing calculations
• Pediatrics: 75 units/kg IV bolus, followed by 20 units/kg/hour infusion

Pharmacokinetics

Contraindications

• History of heparin-induced thrombocytopenia (HIT)
• History of heparin-induced thrombocytopenia and thrombosis (HITT)
• Active major bleeding
• Severe thrombocytopenia
• Hypersensitivity to heparin or pork products
• Uncontrollable bleeding diathesis

Warnings and Precautions

• Spinal/epidural hematoma risk with neuraxial anesthesia
• Heparin-induced thrombocytopenia (HIT) with potential thrombotic complications

• Monitor for signs of bleeding in all patients
• Use with caution in patients with recent surgery, trauma, or bleeding disorders
• Consider alternative anticoagulants in patients with history of HIT
• Risk of osteoporosis with long-term use (>3 months)
• Potential for hyperkalemia due to aldosterone suppression
• Rebound hypercoagulability after discontinuation

Drug Interactions

• Oral anticoagulants (warfarin): Increased bleeding risk
• Antiplatelet agents (aspirin, clopidogrel): Additive bleeding risk
• Thrombolytics (alteplase, streptokinase): Significant bleeding risk
• NSAIDs: Increased bleeding potential

• Digoxin: Heparin may decrease digoxin levels
• Nicotine: May reduce heparin effect
• Antihistamines, digitalis, tetracyclines: May partially counteract heparin
• IV nitroglycerin: May decrease heparin effect

Adverse Effects

• Bleeding complications (5-10%)
• Injection site reactions (pain, erythema, hematoma)
• Mild thrombocytopenia (reversible)

• Major hemorrhage (gastrointestinal, intracranial, retroperitoneal)
• Heparin-induced thrombocytopenia (HIT) (0.5-5%)
• Anaphylactic reactions
• Osteoporosis with long-term use
• Skin necrosis
• Hyperkalemia
• Aldosterone suppression

Monitoring Parameters

• aPTT every 6 hours until therapeutic, then every 24 hours
• Complete blood count with platelets baseline and every 2-3 days
• Hemoglobin/hematocrit regularly
• Signs and symptoms of bleeding
• For HIT: platelet count monitoring essential

• Stool occult blood testing
• Renal function (BUN, creatinine)
• Electrolytes (potassium)
• For long-term therapy: bone density monitoring

Patient Education

• Report any signs of bleeding (unusual bruising, blood in urine/stool, bleeding gums)
• Watch for symptoms of thrombosis (pain, swelling, redness in limbs)
• Inform all healthcare providers about heparin therapy
• Do not take other medications without consulting healthcare provider
• Use soft toothbrush and electric razor to minimize bleeding risk
• Report any allergic reactions immediately
• Understand importance of regular blood tests
• For SC administration: Rotate injection sites and avoid rubbing area

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. Nutescu EA, Shapiro NL, Chevalier A. Heparin: A primer for cardiology practice. J Am Coll Cardiol. 2003;41(5):861-874. 4. FDA Prescribing Information: Heparin Sodium Injection. Updated 2021. 5. 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. 6. Smythe MA, Koerber JM, Mattson JC. The use of heparin in patients with renal impairment. Pharmacotherapy. 2005;25(3):386-393.