Heparin & Enoxaparin in the ED
The two workhorses, by scenario: ACS, acute PE, and VTE prophylaxis, with the renal and obesity modifiers that actually change the order. One rule underneath all of it — UFH is control, enoxaparin is predictability.
All of them lean on antithrombin
Each agent binds and supercharges antithrombin. Molecule size decides which clotting factors get shut off.
- UFH bridges antithrombin to thrombin: blocks both factor IIa and Xa.
- LMWH (enoxaparin) is shorter: mostly factor Xa, some anti-IIa.
- Fondaparinux is a synthetic pentasaccharide: factor Xa only.
What to monitor
- UFH: anti-Xa (heparin assay) or aPTT on a weight-based nomogram; ACT for cath-lab / ECMO doses.
- Enoxaparin: usually none. Check a peak anti-Xa (4 h post-dose) in renal impairment, pregnancy, obesity, or very low weight.
- Fondaparinux: no routine monitoring.
Many centers now prefer anti-Xa over aPTT for UFH: fewer confounders, faster to therapeutic range.
The family, compared
| Agent | Target | Half-life | Renal clearance | Protamine reversal |
|---|---|---|---|---|
| UFH | IIa + Xa | ~60–90 min (IV) | Minimal | Full |
| Enoxaparin | Xa > IIa | ~4–7 h (SC) | Significant | Partial (~60%) |
| Fondaparinux | Xa only | ~17–21 h | Heavy | None |
Half-lives are approximate and lengthen in renal impairment. Confirm dosing and thresholds against your institutional protocol and pharmacy.
The antidote shrinks as the molecule shrinks.
Protamine fully reverses UFH, only partially reverses enoxaparin, and does nothing for fondaparinux. The same gradient runs the other way for half-life and renal clearance.
So when bleeding risk is high, renal function is poor, or a procedure is imminent, the short-acting, titratable, fully reversible, renally-independent choice is unfractionated heparin.
ACS — STEMI / NSTEMI
then 12 units/kg/hr (max 1,000 units/hr)
titrate to aPTT / anti-Xa nomogram
- No prior anticoagulant: 70–100 units/kg IV bolus to target ACT
- Already anticoagulated: additional UFH only as needed to target ACT
- CrCl ≥ 30: 1 mg/kg SQ q12h
- CrCl < 30: 1 mg/kg SQ q24h
- Age < 75: 30 mg IV bolus, then 1 mg/kg SQ q12h (first 2 SQ doses max 100 mg)
- Age ≥ 75: no IV bolus; 0.75 mg/kg SQ q12h (first 2 SQ doses max 75 mg)
- CrCl < 30: 1 mg/kg SQ q24h
Acute pulmonary embolism — treatment
Preferred for many stable PE patients who need parenteral therapy.
- CrCl ≥ 30: 1 mg/kg SQ q12h
- Alternative 1.5 mg/kg SQ daily — but q12h is often preferred for higher-risk PE, obesity, high inpatient clot burden, pregnancy, or cancer
- CrCl < 30: 1 mg/kg SQ q24h, or use UFH IV
then 18 units/kg/hr
titrate to VTE heparin nomogram
- Massive / high-risk PE, hypotension, peri-arrest
- Possible thrombolysis, thrombectomy, ECMO, OR, or procedure
- CrCl < 30, ESRD, dialysis
- High bleeding risk or need for rapid stop / reversal
Inpatient VTE prophylaxis
- CrCl ≥ 30: 40 mg SQ daily
- CrCl < 30: 30 mg SQ daily
- Common protocol: 40 mg SQ q12h
- Alternative: weight-based, often ~0.5 mg/kg daily or q12h
- Use local protocol; consider anti-Xa at weight extremes
- CrCl < 30, ESRD, dialysis
- High bleeding concern
- Frequent procedures expected
- Frail / underweight, where LMWH accumulation is a concern
The BMI ≥ 40 regimen is a common institutional strategy, not a universal guideline-level standard. Follow your hospital protocol.
Dose modifiers
- Enoxaparin generally okay
- Treatment 1 mg/kg q12h · prophylaxis 40 mg daily
- Enoxaparin accumulates
- Treatment → 1 mg/kg q24h · prophylaxis → 30 mg daily
- Strongly consider UFH if unstable, procedural, dialysis, or high bleeding risk
- Enoxaparin usually uses actual body weight
- Avoid arbitrary dose caps unless local protocol says so
- Consider anti-Xa if BMI ≥ 40, very high weight, renal dysfunction, bleeding, or recurrent thrombosis
- BMI < 40: usually standard prophylaxis
- BMI ≥ 40: many hospitals use 40 mg q12h (protocol-dependent)
Elderly / low body weight: the driver is renal function and bleeding risk, not age alone. Calculate CrCl. STEMI fibrinolysis carries a hard age adjustment at ≥ 75. For the frail, underweight, or renally impaired, UFH is often safer and more controllable.
Reversal & bleeding
- UFH: protamine 1 mg per 100 units given in the last ~2–3 h (max ~50 mg/dose, slow IV). Short half-life means stopping the drip often does most of the work.
- Enoxaparin: protamine partially reverses — 1 mg per 1 mg if within 8 h; expect only ~60% anti-Xa neutralization.
- Fondaparinux: no effective antidote; protamine does not work. In life-threatening bleeding consider rFVIIa and expert input.
- Protamine itself can cause hypotension, bradycardia, and anaphylaxis (fish allergy, prior protamine / NPH insulin exposure).
Heparin-induced thrombocytopenia
- Immune PF4–heparin reaction. Platelets fall > 50%, classically day 5–10 (sooner if exposed in the last ~100 days).
- The danger is thrombosis, not bleeding. Use the 4Ts score.
- Stop all heparin — including enoxaparin and line flushes. Start a non-heparin agent (argatroban, bivalirudin, fondaparinux, or a DOAC).
- Don't transfuse platelets prophylactically or start warfarin until platelets recover.
- Risk order: UFH > LMWH > fondaparinux.
Pick the tool for the situation
Unstable PE, cath / OR / thrombolysis possible, severe renal impairment, dialysis, or high bleeding risk.
Stable PE, stable ACS without an immediate procedure, and routine prophylaxis when renal function is adequate.
Always check: indication · actual weight · BMI · CrCl · bleeding risk · procedure plan · platelet count / HIT history · local heparin nomogram.