Unfractionated Heparin 

Feature

UFH (Unfractionated Heparin)

LMWH (Low Molecular Weight Heparin)

Fondaparinux

Examples

Heparin

Enoxaparin, Dalteparin

Fondaparinux

Mechanism

Binds antithrombin (AT) → inhibits IIa (thrombin) + Xa

Preferential Xa inhibition > IIa

Selective Xa inhibition only

Onset

Immediate (IV)

3–5 hr (SC)

2–3 hr

Half-life

Short (1–2 hr)

Intermediate (4–6 hr)

Long (17–21 hr)

Route

IV / SC

SC only

SC only

Bioavailability

Variable (~30%)

High (~90%)

~100%

Monitoring

aPTT(target 1.5–2.5× control)

 (or anti-Xa in ICU)

Usually none (anti-Xa in special cases)

Not required

Dose predictability

Poor

Good

Excellent

Reversal agent

Protamine sulfate (full reversal)

Protamine (partial)

No specific antidote

Renal clearance

No (safe in renal failure)

Yes (dose adjust)

Yes (contraindicated if CrCl <30)

HIT risk

High

Lower

Minimal/negligible

Osteoporosis (long-term)

Yes

Less

Minimal

Use in pregnancy

Safe

Safe

Limited data

Use in obesity

Needs monitoring

Weight-based dosing

Limited data

ICU use

Preferred in unstable pts

Stable ICU pts

Selected cases

Bridging therapy

Yes

Yes

Rare

DVT prophylaxis

Yes

Preferred

Alternative

Acute Coronary Syndrome  use

Yes

Yes (enoxaparin preferred)

Not first-line

Viva Pearls

  • Why UFH in ICU? → short half-life + reversible
  • Why LMWH preferred generally? → predictable PK + less HIT
  • Why fondaparinux avoided in ICU? → no antidote + renal dependence
  • Best drug in HIT? → Fondaparinux (or direct thrombin inhibitors like argatroban)

1. Therapeutic Anticoagulation (Full-dose UFH)

Standard IV Regimen (Most important)

Step

Dose

Bolus

80 units/kg IV

Infusion

18 units/kg/hr IV infusion

 Target Monitoring

  • aPTT target → 1.5–2.5 × control
  • OR
  • Anti-Xa level → 0.3–0.7 IU/mL

 Dose Adjustment

aPTT result

Action

<1.2 × control

Increase infusion + bolus

1.2–1.5 ×

Increase infusion

1.5–2.5 ×

Therapeutic (no change)

2.5–3 ×

Reduce infusion

>3 ×

Stop infusion temporarily

Check aPTT every 6 hours until stable

  • Use anti-Xa instead of aPTT in:
    • Sepsis
    • High factor VIII states
    • Liver disease
    • DIC

2.  DVT Prophylaxis (Low-dose UFH)

Regimen

Dose

Standard

5000 units SC every 8–12 hours

Special situations

  • Obesity → consider 7500 U SC TDS
  • High bleeding risk → mechanical prophylaxis preferred

3. Acute Coronary Syndrome (ACS)

Step

Dose

Bolus

60–70 U/kg (max 4000–5000 U)

Infusion

12–15 U/kg/hr (max ~1000 U/hr)

Target:

  • aPTT → 50–70 sec (institution dependent)

4.  Pulmonary Embolism / DVT Treatment

  • 80 U/kg bolus + 18 U/kg/hr infusion

5.  ECMO / CRRT Anticoagulation

ECMO 

  • Bolus: 50–100 U/kg
  • Infusion: 7–20 U/kg/hr

Targets:

  • ACT → 180–220 sec
  • Anti-Xa → 0.3–0.7

CRRT

  • Bolus: 500–1000 U (optional)
  • Infusion: 5–10 U/kg/hr

7.  Bridging to Warfarin

  • Start UFH + Warfarin together
  • Continue UFH for ≥5 days AND INR ≥2 for 24 h

10.  Complication-based Adjustments

Bleeding

  • Stop UFH
  • Give Protamine sulfate
    • Dose: 1 mg per 100 units heparin (last 2–3 hr dose)

Suspected HIT

  • Stop UFH immediately
  • Switch to:
    • Argatroban
    • or Fondaparinux