What are the indications for Enoxheparin (Enoxaparin) in patients at high risk of thromboembolic events?

Enoxaparin Indications

Enoxaparin is indicated for venous thromboembolism (VTE) prophylaxis in hospitalized medical patients and surgical patients at moderate-to-high risk, treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE), bridging anticoagulation during interruption of vitamin K antagonist therapy in high-risk patients, and extended prophylaxis in cancer patients undergoing major surgery or receiving thrombogenic chemotherapy. 1, 2

VTE Prophylaxis in Hospitalized Medical Patients

• Enoxaparin 40 mg subcutaneously once daily is recommended for hospitalized patients with acute medical illness or reduced mobility, particularly those with cancer, for the duration of hospital stay or until fully ambulatory. 2, 3
• This prophylactic regimen reduces the incidence of VTE from 14.9% to 5.5% compared to placebo in medically ill patients at increased risk. 3
• For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the prophylactic dose to 30 mg subcutaneously once daily. 1, 2

VTE Prophylaxis in Surgical Patients

Moderate-Risk Surgery

• Enoxaparin 40 mg subcutaneously once daily starting after surgery, or 5,000 units of unfractionated heparin every 12 hours, is recommended for moderate-risk surgical patients. 1
• Treatment should continue for at least 7-10 days postoperatively. 1, 2

High-Risk Surgery (Major Abdominal/Pelvic Cancer Surgery)

• Enoxaparin 40 mg subcutaneously once daily is recommended, with extended prophylaxis continued for up to 4 weeks postoperatively in patients with high-risk features such as restricted mobility, obesity, or history of VTE. 1, 2
• Extended prophylaxis reduces VTE risk by 60% without increasing major bleeding in cancer surgery patients. 2

Very High-Risk Surgery (Urologic Surgery)

• Enoxaparin 40 mg subcutaneously daily (30 mg if creatinine clearance <30 mL/min) combined with pneumatic compression devices is recommended for very high-risk patients. 1
• For patients with body weight >150 kg, consider increasing the prophylactic dose to 40 mg subcutaneously every 12 hours. 1

Treatment of Acute DVT and PE

• Enoxaparin 1 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg subcutaneously once daily is recommended for initial treatment of acute DVT or PE. 2, 4
• Initial treatment typically lasts 5-10 days, overlapping with warfarin until INR >2.0 for 2 consecutive days if transitioning to oral anticoagulation. 2
• For cancer-associated VTE, continue enoxaparin monotherapy for at least 6 months, and indefinitely while cancer remains active or under treatment. 1, 2
• After the first month of cancer treatment, consider dose reduction to 75-80% of initial dose. 2

Bridging Anticoagulation During VKA Interruption

High-Risk Patients Requiring Bridging

• Therapeutic-dose enoxaparin (1 mg/kg subcutaneously every 12 hours) is recommended for high-risk patients during interruption of vitamin K antagonist therapy. 1
• High-risk patients include those with:
  • Mechanical mitral valve or older-generation mechanical aortic valve 1
  • Atrial fibrillation with CHADS2 score ≥5 or recent stroke/TIA (within 3 months) 1
  • VTE within the past 3 months 1
• This bridging regimen is associated with a low (1%-2%) incidence of arterial thromboembolism. 1

Moderate-Risk Patients

• The decision to bridge with enoxaparin in moderate-risk patients (CHADS2 score 3-4, mechanical bileaflet aortic valve with additional risk factors, or VTE within 3-12 months) should be individualized based on bleeding risk of the planned procedure. 1
• For low-bleeding-risk procedures, consider therapeutic or intermediate-dose bridging (enoxaparin 40 mg twice daily). 1
• For high-bleeding-risk procedures (major cardiac surgery, carotid endarterectomy), consider no bridging. 1

Special Indications in Cancer Patients

Multiple Myeloma Receiving Immunomodulatory Therapy

• Enoxaparin 40 mg subcutaneously once daily OR aspirin 81-325 mg daily is recommended for patients with multiple myeloma receiving thalidomide or lenalidomide-based regimens. 1
• Use enoxaparin (not aspirin) for patients with ≥2 individual or disease-related VTE risk factors, or those receiving high-dose dexamethasone (≥480 mg/month) or multiagent chemotherapy. 1
• LMWH is superior to warfarin in reducing grade 3-4 thromboembolic events in older patients (≥65 years) receiving bortezomib, melphalan, prednisone, and thalidomide. 1

Ambulatory Cancer Patients on Chemotherapy

• Consider enoxaparin prophylaxis in ambulatory cancer patients at high risk for VTE based on assessment of risk factors, particularly those with pancreatic cancer or advanced cancer receiving chemotherapy. 1

Dosing Adjustments for Special Populations

Obesity (BMI >30 kg/m²)

• Consider intermediate-dose prophylaxis with enoxaparin 40 mg subcutaneously every 12 hours or weight-based dosing at 0.5 mg/kg every 12 hours. 2
• For therapeutic dosing in patients with BMI ≥40 kg/m², use 0.8 mg/kg subcutaneously every 12 hours. 2

Renal Impairment

• For creatinine clearance <30 mL/min, reduce prophylactic dose to 30 mg subcutaneously once daily and therapeutic dose to 1 mg/kg every 24 hours (instead of every 12 hours). 2
• Enoxaparin clearance is reduced by 44% in severe renal impairment, significantly increasing bleeding risk. 2, 5
• Monitor anti-Xa levels (target 0.5-1.5 IU/mL) in patients with severe renal impairment on prolonged therapy, measured 4-6 hours after dosing. 2

Pregnancy with Obesity

• For pregnant women with class III obesity requiring thromboprophylaxis, use intermediate-dose enoxaparin 0.5 mg/kg subcutaneously every 12 hours. 2

Advantages Over Unfractionated Heparin

• Enoxaparin offers better bioavailability, longer half-life, more predictable anticoagulation effect without routine monitoring, and significantly lower risk of heparin-induced thrombocytopenia compared to unfractionated heparin. 2, 6, 4
• Enoxaparin enables once- or twice-daily subcutaneous dosing, facilitating outpatient treatment. 4
• Lower risk of osteopenia with long-term use compared to unfractionated heparin. 2

Common Pitfalls and Contraindications

• Never use standard-dose enoxaparin in severe renal impairment (CrCl <30 mL/min) without dose adjustment; consider unfractionated heparin instead due to its shorter half-life and reversibility. 2, 5
• For planned neuraxial anesthesia, withhold enoxaparin for 24 hours before catheter manipulation and resume no earlier than 2 hours after manipulation to avoid spinal hematoma. 1, 2
• Enoxaparin is contraindicated in patients with documented heparin-induced thrombocytopenia or positive antiplatelet antibody tests. 5
• Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia. 2
• Standard fixed dosing may be inadequate in obese patients and excessive in very low-weight patients. 2

When to Use Unfractionated Heparin Instead

• Use unfractionated heparin rather than enoxaparin when creatinine clearance <30 mL/min, high bleeding risk requiring rapid reversibility with protamine, or active bleeding is present. 5
• Unfractionated heparin is significantly less expensive than enoxaparin, making it preferable when cost-effectiveness is a priority. 5