Enoxaparin
Enoxaparin
Generic Name
Enoxaparin
Mechanism
- Selective inhibition of factor Xa: Enoxaparin binds antithrombin (AT) and accelerates its inhibition of free factor Xa more than thrombin.
- Reduced thrombin generation: By partially inhibiting thrombin (via factor Xa reduction), it decreases fibrin formation while preserving some antithrombin activity on thrombin.
- Less consumption of AT compared with unfractionated heparin (UFH), leading to more predictable anticoagulation.
Pharmacokinetics
| Property | Typical Values (IV) | Typical Values (SC) | Notes |
| Bioavailability | 100 % | 75‑85 % | SC absorption is time‑dependent; peak ~1.5–2 h. |
| Volume of distribution | 0.3 L/kg | 0.3 L/kg | Little protein binding (~30 %). |
| Half‑life | 2.5–3 h (renal) | 4–5 h | Prolonged in renal insufficiency. |
| Clearance | Renal (creatinine clearance 50–60 mL/min) | Renal (30–120 mL/min) | 80 % renally excreted. |
| Metabolism | None significant | None significant | Mainly filtered by glomerulus. |
Indications
- Venous thromboembolism (VTE) prevention
- Post‑operative prophylaxis after hip/knee arthroplasty, major abdominal surgery, or prolonged immobilization.
- Treatment of acute symptomatic DVT and PE
- *Therapeutic* dosing 1 mg/kg SC BID or IV 0.5 mg/kg q12h.
- Pre‑/post‑percutaneous coronary intervention (PCI)
- 2 mg/kg IV bolus (≥ 70 kg) followed by 1 mg/kg SC BID for 48 h.
- Unstable angina and STEMI (up to 72 h)
- 1 mg/kg IV bolus, 1 mg/kg SC BID.
- Hypercoagulable states (e.g., antiphospholipid syndrome) – as an alternative to warfarin in select patients.
Contraindications
- Absolute
- Active major bleeding.
- Known hypersensitivity to enoxaparin or other LMWHs.
- Severe thrombocytopenia (< 50 × 10⁹/L).
- Heparin‐induced thrombocytopenia (HIT) history.
- Relative
- Severe renal impairment (CrCl < 30 mL/min) – dose adjustment or alternative.
- Recent major surgery or trauma (high bleeding risk).
- Moderate to severe hepatic impairment (↑ coagulopathy risk).
- Warnings
- HIT risk; monitor platelet count 5–10 days post‑initiation.
- Osteoarthritis: avoid intra‑articular injection.
- Pregnancy: considered safe; no transplacental passage.
Dosing
| Indication | Weight‑Based Regimen | Administration | Notes |
| VTE prophylaxis | 40 mg SC once daily (≤ 90 kg) or 30 mg SC once daily (≥ 90 kg) | Subcutaneously, thigh/abdomen | Once daily; weight < 30 kg: 30 mg SC once daily. |
| Therapeutic treatment (DVT/PE) | 1 mg/kg SC BID (≤ 90 kg) or 1 mg/kg IV q12h | 1 mg/kg IV 2 mg/kg SC loading (≥ 70 kg) | Follow with SC maintenance. |
| PCI / Acute coronary syndrome | 2 mg/kg IV bolus (≥ 70 kg), then 1 mg/kg SC BID | IV bolus, SC thereafter | 48 h SC therapy after IV period. |
| Renal impairment (CrCl 30–50 mL/min) | 0.5 mg/kg SC BID | Adjust load/dose | Monitor anti‑Xa weekly. |
| Severe renal impairment (CrCl < 30 mL/min) | Reduce dose to 1 mg/kg SC BID with dose‑dependent considerations | Monitor anti‑Xa weekly | Consider LMWH alternative (e.g., fondaparinux). |
*All SC injections should be administered in alternate sites, avoiding the abdomen within 8 h of a previous injection.*
Adverse Effects
- Bleeding – major and minor (e.g., epistaxis, gum bleeds).
- Thrombocytopenia – early (platelets drop 1‑2 days) ≥ 50 % decline may suggest HIT.
- Osteopenia/osteoporosis – prolonged use (> 6 weeks) in elderly.
- Heparin‑induced thrombocytopenia (HIT) – severe; requires immediate discontinuation.
- Anaphylactic reactions – rare.
Monitoring
| Parameter | Frequency | Target/Notes |
| Anti‑Xa activity | 3–4 h post SC dose (peak) | 0.3–0.7 IU/mL (therapeutic) |
| Platelet count | Baseline + day 5–10 of therapy | ≥ 50 × 10⁹/L; > 50 % drop = HIT suspicion |
| Renal function | Baseline, then as clinically indicated | Adjust dose if CrCl < 30 mL/min |
| Clinical assessment | Daily | Monitor for signs of bleeding or neurologic symptoms |
| Coagulation labs (PT/INR, aPTT) | Not routinely required | Only for crossover to warfarin or other anticoagulants |
Clinical Pearls
- Weight‑based dosing vs. fixed regimens: Fixed 40 mg SC daily works for most adults, but weight ≥ 90 kg receives 30 mg daily—avoid under‑dosing in overweight/obese patients.
- Renal dysfunction: Enoxaparin’s half‑life is prolongated ≈ 2‑3 hr per 10 mL/min decline. Use anti‑Xa monitoring or switch to UFH if CrCl 120 kg)**: Double standard prophylactic dose (80 mg/day) increases efficacy for VTE without substantially raising bleeding risk.
- HIT surveillance: If platelet count falls below 70 % of baseline after day 5, stop enoxaparin, confirm with a PF4‑ELISA, and commence a non‑heparin anticoagulant.
- Pregnancy: Enoxaparin is classified FDA class B; preferred over UFH due to longer half‑life and fewer injections, but monitor for postpartum hemorrhage.
- Intervertebral disc injections: Avoid enoxaparin for >48 h prior to epidural/spinal procedures to minimize epidural hematoma risk.
> Key takeaway: Enoxaparin’s predictable bioavailability, weight‑based dosing, and minimal monitoring needs make it a first‑line anticoagulant for VTE prophylaxis and treatment, but vigilance for bleeding, thrombocytopenia, and renal status remains essential.