Pros:
- Predictable anticoagulant effect (less monitoring needed)
- Longer half-life → once/twice daily SC dosing
- Safe in pregnancy (does not cross placenta)
- Lower HIT risk (0.2% in surgical patients)
Cons:
- Renal clearance → risk of accumulation in renal impairment
- Less effective protamine reversal (60–75%)

Unfractionated Heparin (UFH)

Pros:
- Short half-life (60–90 min) → rapid adjustments/discontinuation
- Fully reversible with protamine sulfate
- Preferred in severe kidney impairment
Cons:
- IV administration with frequent APTT monitoring required
- Higher HIT risk (2.6% in surgical patients)

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Reversal Agent: Protamine Sulfate

For LMWH (e.g., enoxaparin):

<8 hrs: 1 mg protamine per 1 mg enoxaparin (max 50 mg)
8–12 hrs: 0.5 mg protamine per 1 mg enoxaparin (max 50 mg)
12 hrs: Reversal may not be needed; check anti-Xa levels

For UFH:

1 mg protamine per 100 units UFH given in the last 3 hrs (max 50 mg)
Repeat 0.5 mg per 100 units if APTT remains elevated

Notes:

Protamine has a short half-life (~7 min) → administer slowly to prevent hypotension/allergic reactions

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Specialist Referral Indications

LMWH

Renal impairment (CrCl <30 mL/min)
Active bleeding/thrombosis during therapy
Low body weight (<50 kg) or obesity (>150 kg or BMI >40 kg/m²)
Pregnancy

UFH

Complex management (e.g., surgery, high-risk bleeding, or suspected HIT)

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Overdose Treatment

LMWH

<8 hrs: Full-dose protamine (1 mg per 1 mg enoxaparin)
8–12 hrs: Half-dose protamine (0.5 mg per 1 mg enoxaparin)
12 hrs: Reversal may not be needed; check anti-Xa level

UFH

Calculate UFH given in last 3 hrs → 1 mg protamine per 100 units UFH (max 50 mg)
Repeat doses if APTT remains elevated

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Notes

Monitor for adverse effects of protamine (e.g., hypotension, allergic reactions)
Protamine reversal is more effective for UFH than LMWH
Regular anticoagulation monitoring reduces overdose and bleeding risks

Heparin: LMWH vs UFH

Low Molecular Weight Heparin (LMWH)

Pros:
- Predictable anticoagulant effect → less frequent monitoring of anti-Xa levels in standard use
- Longer half-life → once- or twice-daily subcutaneous dosing
- Safe in pregnancy (does not cross the placenta)
- Lower HIT (heparin-induced thrombocytopenia) risk (~0.2% in surgical patients)
Cons:
- Renal clearance → risk of accumulation in renal impairment (CrCl <30 mL/min)
- Partial protamine reversal (~60–75% efficacy)

Unfractionated Heparin (UFH)

Pros:
- Short half-life (60–90 minutes) → easy titration/cessation (IV infusion)
- Fully reversible with protamine sulfate
- Preferred in severe kidney impairment (not reliant on renal clearance)
Cons:
- Requires IV infusion and frequent APTT monitoring (inpatient setting)
- Higher risk of HIT (~2.6% in surgical patients)

Reversal Agent: Protamine Sulfate

Mechanism: Forms stable complexes with heparin, neutralising anticoagulant effect
Administration: Give slow IV infusion over 10 minutes to reduce hypotension/anaphylactic reactions
Half-Life: ~7 minutes → repeated doses may be required if prolonged effect needed

LMWH (e.g. Enoxaparin) Reversal

<8 hrs since dose: 1 mg protamine per 1 mg enoxaparin (max 50 mg total)
8–12 hrs since dose: 0.5 mg protamine per 1 mg enoxaparin (max 50 mg total)
12 hrs: Reversal may not be necessary; consider checking anti-Xa levels
Note: Protamine neutralises ~60–75% of LMWH activity due to partial binding

UFH Reversal

Calculate total units of UFH given in the last 3 hrs
1 mg protamine per 100 units UFH (max 50 mg at once)
Repeat with 0.5 mg protamine per 100 units if APTT remains elevated

Specialist Referral Indications

LMWH

Significant renal impairment (CrCl <30 mL/min) → risk of drug accumulation
Active bleeding or new thrombosis while on therapy
Low body weight (<50 kg) or obesity (>150 kg or BMI >40 kg/m²) → unpredictable pharmacokinetics
Pregnancy (optimise dosing, possible anti-Xa monitoring)

UFH

Complex cases: e.g. pending surgery with high bleeding risk, suspected or confirmed HIT, or complex bridging scenarios

Overdose Treatment

LMWH

<8 hrs: Full-dose protamine (1 mg per 1 mg enoxaparin)
8–12 hrs: Half-dose protamine (0.5 mg per 1 mg enoxaparin)
12 hrs: Often no reversal needed; check anti-Xa levels if clinically relevant

UFH

Calculate total units given in last 3 hrs
1 mg protamine per 100 units UFH (max 50 mg)
Repeat if APTT remains high after initial dose

Notes

Monitor for protamine side effects: hypotension, bradycardia, allergic reactions (especially in diabetics or fish allergy)
Protamine reversal is more effective for UFH than LMWH (complete vs partial neutralisation)
Regular anticoagulation monitoring (APTT for UFH, anti-Xa for LMWH in certain cases) reduces risk of overdose/bleeding

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