Is enoxaparin (low molecular weight heparin) indicated?

Is Enoxaparin Indicated?

Enoxaparin is indicated for multiple clinical scenarios including venous thromboembolism treatment and prophylaxis, acute coronary syndromes (unstable angina/NSTEMI), and perioperative DVT prevention, with specific dosing and monitoring requirements based on the clinical context.

Primary Indications for Enoxaparin

Venous Thromboembolism (VTE) Treatment

• Enoxaparin is the preferred first-line agent for acute DVT treatment over IV unfractionated heparin (Grade 2C) and subcutaneous unfractionated heparin (Grade 2B). 1
• Standard dosing is 1 mg/kg subcutaneously twice daily or 1.5 mg/kg once daily, with once-daily dosing preferred (Grade 2C). 1
• Continue enoxaparin for minimum 5 days AND until INR ≥2.0 for at least 24 hours when transitioning to warfarin. 1
• In cancer patients with VTE, enoxaparin is strongly preferred over warfarin for extended therapy (Grade 2B), with dalteparin showing superior efficacy (4% vs 11% recurrence). 1

Acute Coronary Syndromes (Unstable Angina/NSTEMI)

• Enoxaparin is indicated as a substitute for unfractionated heparin in high-risk patients with UA/NSTEMI, with growing evidence supporting this substitution. 2
• For patients ≤75 years: 30 mg IV bolus followed by 1 mg/kg subcutaneously every 12 hours. 3
• For patients >75 years: 0.75 mg/kg subcutaneously every 12 hours without initial IV bolus (due to increased intracranial hemorrhage risk with pre-hospital administration in elderly patients receiving fibrinolytics). 4, 3

Perioperative VTE Prophylaxis

• In cancer patients undergoing major surgery, enoxaparin 4000 units (40 mg) once daily is recommended starting perioperatively. 2
• For elective major abdominal or pelvic cancer surgery, continue prophylaxis for up to 1 month post-discharge. 2
• For laparotomy, laparoscopy, thoracotomy, or thoracoscopy lasting >30 minutes, continue enoxaparin for at least 10 days postoperatively. 2

Medical Inpatients

• Enoxaparin 40 mg/day subcutaneously is indicated for hospitalized cancer patients confined to bed with acute medical complications. 2
• In medically ill patients at increased risk for thromboembolism, enoxaparin 40 mg/day significantly reduces VTE incidence (5.5% vs 14.9% placebo, p<0.001). 5

Critical Contraindications and Precautions

Absolute Contraindications

• Active major bleeding. 4
• Thrombocytopenia with positive in vitro antiplatelet antibodies in presence of enoxaparin. 4
• Known hypersensitivity to enoxaparin, heparin, sulfites, benzyl alcohol, or pork products. 4

Severe Hepatic Dysfunction

• Exercise extreme caution when INR ≥1.5 (indicating impaired hepatic synthetic function), not simply elevated transaminases alone. 3
• Elevated transaminases represent hepatocellular injury and are recognized adverse reactions, not contraindications. 3
• When liver failure with INR ≥1.5 is present, consider unfractionated heparin as it allows more precise titration via aPTT monitoring. 3

Renal Impairment

• For creatinine clearance <30 mL/min, reduce dose to 1 mg/kg once daily (enoxaparin has delayed clearance due to longer half-life). 1, 4, 3
• Alternatively, use IV UFH in severe renal impairment. 1

Key Advantages Over Unfractionated Heparin

• Significantly lower risk of heparin-induced thrombocytopenia (HIT), eliminating routine platelet monitoring in most patients (Grade 2B). 1
• No laboratory monitoring required (unlike IV heparin requiring aPTT checks every 4 hours). 1
• Longer plasma half-life and higher bioavailability enabling once or twice-daily subcutaneous dosing. 6
• Enables outpatient treatment for acute DVT. 6

When to Use IV Unfractionated Heparin Instead

• Massive PE causing hypotension (systolic BP <90 mmHg) where thrombolytic therapy is considered. 1
• Situations requiring immediate, titratable anticoagulation with rapid reversibility. 1
• Severe hepatic dysfunction with INR ≥1.5. 3
• Combined renal insufficiency and high bleeding risk (consider bivalirudin as alternative). 3

Monitoring Requirements

• Platelet monitoring every 2-3 days from day 4-14 is required when using any form of unfractionated heparin, but NOT routinely needed for enoxaparin. 1
• Monitor hemoglobin, hematocrit, and platelet count every 2-3 days for first 14 days after initiating enoxaparin. 4
• Serial hepatic function tests (ALT, AST, bilirubin, INR, albumin) to distinguish hepatocellular injury from synthetic dysfunction in patients with liver disease. 3

Special Populations

Cancer Patients

• Enoxaparin is preferred over warfarin for extended VTE therapy in cancer patients (Grade 2B). 1
• Routine prophylaxis for ambulatory patients receiving palliative chemotherapy is NOT recommended. 2
• Consider prophylaxis in myeloma patients receiving thalidomide plus dexamethasone or chemotherapy (LMWH or adjusted-dose warfarin with INR ~1.5). 2

Pregnancy

• Enoxaparin is the anticoagulant of choice throughout pregnancy (Grade 2C). 1

Obese Patients

• Use weight-based dosing without capping maximum doses (Grade 2B). 1

Common Pitfalls to Avoid

• Do not delay warfarin initiation—start on day 1 of heparin therapy (Grade 2C). 1
• Do not use enoxaparin 20 mg/day for VTE prophylaxis (no reduction in thromboembolism vs placebo). 5
• Avoid pre-hospital administration in elderly patients (>75 years) receiving fibrinolytics due to significantly increased intracranial hemorrhage risk. 4
• Enoxaparin is unlikely to be dialyzable due to high plasma protein binding; in active bleeding, discontinue and administer blood products. 4

Adverse Event Profile

• Major bleeding occurs in 0.1-0.7% of orthopedic surgery patients (comparable to UFH). 4
• Clinically relevant non-major bleeding in 2.6-3.3% of patients. 4
• Most frequent adverse events: hemorrhage (17.4% vs 14.3% placebo), injection site hematoma, anemia, fever, peripheral edema. 5
• Rare: reactive thrombocytosis (resolves after discontinuation). 7
• No evidence of drug-associated liver toxicity in phase III trials up to 5 weeks. 4