What is the typical dosing regimen for Unfractionated (UF) heparin for therapeutic anticoagulation?

Unfractionated Heparin Dosing for Therapeutic Anticoagulation

For therapeutic anticoagulation with unfractionated heparin, administer an initial IV bolus of 80 units/kg followed by a continuous infusion of 18 units/kg/hour, with aPTT monitoring at 6 hours and dose adjustments to maintain aPTT at 1.5-2.5 times control value (typically 60-85 seconds). 1, 2, 3

Initial Dosing Regimen

Intravenous Route (Preferred)

• Bolus dose: 80 units/kg IV push 1, 2, 3, 4
• Continuous infusion: 18 units/kg/hour (approximately 20,000-40,000 units per 24 hours for average adults) 1, 2, 3, 4
• This weight-based nomogram achieves therapeutic anticoagulation more rapidly than lower-dose regimens (60 units/kg bolus with 12 units/kg/hour infusion) 5

Subcutaneous Route (Alternative)

• Loading dose: 333 units/kg SC 1, 2
• Maintenance dose: 250 units/kg SC every 12 hours 1, 2, 4
• This route is appropriate when IV access is unavailable or for outpatient management 1

Context-Specific Modifications

• With fibrinolytic therapy: 60 units/kg IV bolus (maximum 4,000 units) followed by 12 units/kg/hour infusion (maximum 1,000 units/hour) for 24-48 hours 1
• With GP IIb/IIIa inhibitors: Reduce bolus to 50-70 units/kg 1, 3
• Acute coronary syndromes without PCI: 60 units/kg bolus (max 4,000 units) followed by 12 units/kg/hour (max 1,000 units/hour) 1

Monitoring Protocol

Timing and Target Range

• First aPTT measurement: 6 hours after initial bolus 1, 2, 3, 4
• Target aPTT: 1.5-2.5 times control value (typically 60-85 seconds, though this varies by laboratory reagent) 1, 2, 3, 4
• Subsequent monitoring: Every 4-6 hours until stable in therapeutic range, then daily 2, 3, 4
• Failure to achieve therapeutic aPTT within 24 hours increases risk of recurrent thromboembolism 15-fold 3

Dose Adjustment Nomogram

Use the following standardized adjustments based on aPTT results 2, 3:

• aPTT < 35 seconds: Give 80 units/kg bolus, increase infusion by 4 units/kg/hour
• aPTT 35-45 seconds: Give 40 units/kg bolus, increase infusion by 2 units/kg/hour
• aPTT 46-70 seconds: No change (therapeutic range)
• aPTT 71-90 seconds: Decrease infusion by 2 units/kg/hour
• aPTT > 90 seconds: Hold infusion for 1 hour, then decrease by 3 units/kg/hour

Additional Laboratory Monitoring

• Platelet counts: Monitor periodically throughout therapy to detect heparin-induced thrombocytopenia 2, 4
• Hematocrit and occult blood in stool: Check periodically regardless of administration route 4

Special Populations

Morbidly Obese Patients

• Standard weight-based protocols with maximum dose caps cause significant delays in achieving therapeutic anticoagulation 6
• Use a modified dosing weight: IBW + 0.3(ABW - IBW) or IBW + 0.4(ABW - IBW) 6, 7
• Alternatively, use a capped dosing weight (e.g., 120 kg) rather than actual body weight to avoid supratherapeutic levels while preventing subtherapeutic dosing 7

Renal Insufficiency

• UFH is preferred over LMWH in severe renal failure (CrCl < 25-30 mL/min) because it is primarily metabolized by the liver 2, 3
• No dose adjustment required for renal impairment 1
• Consider monitoring with anti-Xa activity (target 0.3-0.7 units/mL) if available 1, 2

Pediatric Patients

• Initial bolus: 75-100 units/kg IV over 10 minutes 4
• Maintenance infusion:
  • Infants < 2 months: 25-30 units/kg/hour (highest requirements, average 28 units/kg/hour) 4
  • Children > 1 year: 18-20 units/kg/hour 4
• Target aPTT: 60-85 seconds (corresponding to anti-Factor Xa level of 0.35-0.70) 4
• Use preservative-free formulations in neonates and infants 4

Critical Pitfalls to Avoid

Laboratory-Specific Considerations

• Different aPTT reagents have vastly different responsiveness to heparin 2, 3
• The therapeutic range must be calibrated to your specific laboratory's reagent 2, 3
• Do not assume 60-85 seconds is universally therapeutic without local validation 3

Pharmacokinetic Considerations

• Heparin clearance is dose-dependent and saturable at therapeutic doses, resulting in nonlinear pharmacokinetics 2, 3
• Heparin half-life may be significantly shortened in patients with pulmonary embolism (as short as 40 minutes vs. 84 minutes in other VTE patients) 8
• Large inter-individual variations exist in both heparin clearance and aPTT response 8

Drug Interactions and Contraindications

• Never switch between UFH and enoxaparin during treatment due to increased bleeding risk 1
• Heparin-induced thrombocytopenia is an absolute contraindication to continued heparin use 2, 3
• Switch immediately to alternative anticoagulants (argatroban, danaparoid, or fondaparinux) if HIT is suspected 2, 3

Dosing Errors

• Avoid using maximum dose caps in standard protocols for obese patients, as this delays therapeutic anticoagulation 6
• Do not use intramuscular administration due to frequent hematoma formation 4
• When using subcutaneous route, rotate injection sites and use deep subcutaneous (intrafat) technique above iliac crest or in abdominal fat layer 4