What is enoxaparin?

What is Enoxaparin?

Enoxaparin is a low-molecular-weight heparin (LMWH) derived from unfractionated heparin that acts primarily as an indirect Factor Xa inhibitor with a 4:1 ratio of anti-Xa to anti-thrombin activity, offering more predictable anticoagulation than unfractionated heparin without requiring routine laboratory monitoring. 1

Mechanism of Action

• Enoxaparin binds to antithrombin III, forming a complex that inhibits Factor Xa and, to a lesser extent, thrombin (Factor IIa), preventing clot formation 2
• The drug exhibits greater activity against Factor Xa than thrombin, with an ex vivo 4:1 ratio of Factor Xa to thrombin activity 1
• Unlike unfractionated heparin, enoxaparin has reduced binding to plasma proteins, resulting in a more predictable anticoagulant effect 1

Pharmacokinetic Advantages Over Unfractionated Heparin

• Enoxaparin has a longer plasma half-life (approximately 4-7 hours) compared to unfractionated heparin, allowing for once or twice daily subcutaneous dosing without intravenous infusion 3, 4
• The drug demonstrates higher bioavailability and a linear dose-response relationship, eliminating the need for activated partial thromboplastin time (aPTT) monitoring in most patients 3, 4
• Clearance is delayed in renal dysfunction, requiring dose adjustment in patients with creatinine clearance <30 mL/min 1, 5

Clinical Indications and Dosing

Venous Thromboembolism Treatment

• Standard therapeutic dosing is 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily 6
• For severe renal impairment (CrCl <30 mL/min), reduce to 1 mg/kg subcutaneously once daily 5
• Enoxaparin demonstrates equivalent efficacy to unfractionated heparin for DVT treatment with similar rates of recurrent VTE (2.9% vs 4.1%) and major bleeding (1.3% vs 2.1%) 6

Acute Coronary Syndromes

• In unstable angina and non-ST-elevation MI, enoxaparin 1 mg/kg twice daily is superior to unfractionated heparin in reducing death, MI, or recurrent angina 1, 7
• For patients <75 years with normal renal function, standard dosing is 1 mg/kg subcutaneously every 12 hours 5
• For patients ≥75 years, reduce to 0.75 mg/kg every 12 hours without IV bolus regardless of renal function 5

VTE Prophylaxis

• For high-risk surgical patients (hip/knee replacement), 30 mg twice daily postoperatively or 40 mg once daily starting preoperatively 8
• For medical patients at increased risk, 40 mg once daily reduces VTE incidence from 14.9% to 5.5% compared to placebo 2
• In severe renal impairment, reduce prophylactic dose to 30 mg once daily 5

Safety Profile and Monitoring

Bleeding Risk

• Major bleeding rates are similar to unfractionated heparin (1.3-1.7% vs 2.1%) in most clinical settings 6, 7
• Patients with severe renal impairment (CrCl <30 mL/min) have a 2-3 fold increased bleeding risk with standard dosing, mandating dose reduction 6, 5
• Minor bleeding complications occur more frequently than with unfractionated heparin but are generally well-tolerated 7

Heparin-Induced Thrombocytopenia (HIT)

• The risk of HIT is significantly lower with enoxaparin compared to unfractionated heparin due to reduced binding to platelet Factor 4 1
• Routine platelet monitoring is not required for most patients, unlike unfractionated heparin 1
• In the HORIZONS trial, thrombocytopenia occurred in 10.4% with bivalirudin versus 13.1% with heparin plus glycoprotein IIb/IIIa inhibitors 1

When to Monitor Anti-Xa Levels

• Routine anti-Xa monitoring is not necessary for most patients 6
• Consider monitoring in severe renal impairment (CrCl <30 mL/min), extreme obesity (BMI ≥40 kg/m²), or pregnancy 6, 5
• Measure peak anti-Xa levels 4-6 hours after dosing, only after 3-4 doses have been administered 6, 5
• Target therapeutic anti-Xa range is 0.5-1.5 IU/mL 5

Practical Advantages in Clinical Practice

• Subcutaneous administration enables outpatient treatment of DVT and PE, reducing hospitalization costs while maintaining efficacy and safety 3, 4
• No need for continuous intravenous infusion or aPTT monitoring simplifies nursing care and allows home self-injection 3, 4
• In cancer patients, enoxaparin demonstrates superior efficacy to warfarin with lower rates of recurrent VTE or major bleeding (10.5% vs 21.1%) 6

Important Caveats and Contraindications

• Avoid switching between enoxaparin and unfractionated heparin mid-treatment, as this increases bleeding risk 5
• Withhold enoxaparin 10-12 hours before neuraxial anesthesia to prevent spinal hematoma 5
• Exercise extreme caution in elderly patients (≥70 years) with renal insufficiency due to drug accumulation risk 5
• For extended anticoagulation therapy beyond the acute phase, reduce dose to 75-80% of the initial therapeutic dose 6