What is the dosing regimen for unfractionated heparin (UFH)?

Unfractionated Heparin Dosing

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 dose adjustments based on aPTT monitoring to maintain a therapeutic range of 1.5-2.5 times control (approximately 46-70 seconds). 1, 2, 3

Intravenous Administration

Initial Dosing

• Bolus: 80 units/kg IV (maximum 4000-5000 units) 1, 2, 3
• Continuous infusion: 18 units/kg/hour (maximum 1000 units/hour) 1, 2, 3
• This weight-based approach is superior to fixed dosing and achieves therapeutic anticoagulation more rapidly than lower-dose regimens 1, 4

Monitoring Protocol

• First aPTT: Measure 6 hours after initiating therapy 2, 5, 3
• Target range: aPTT 1.5-2.5 times control (approximately 46-70 seconds), corresponding to anti-factor Xa levels of 0.3-0.7 IU/mL 1, 2
• Frequency: Check aPTT every 4-6 hours until stable in therapeutic range, then daily 2, 5, 3
• Platelet monitoring: Check platelet counts daily throughout therapy to detect heparin-induced thrombocytopenia 2, 5, 3

Dose Adjustment Nomogram

Use the following standardized adjustments based on aPTT results 1, 2:

• aPTT <35 seconds (<1.2× control): Give 80 units/kg bolus, increase infusion by 4 units/kg/hour 1, 2
• aPTT 35-45 seconds (1.2-1.5× control): Give 40 units/kg bolus, increase infusion by 2 units/kg/hour 1, 2
• aPTT 46-70 seconds (1.5-2.3× control): No change—therapeutic range 1, 2
• aPTT 71-90 seconds (2.3-3.0× control): Decrease infusion by 2 units/kg/hour 1, 2
• aPTT >90 seconds (>3.0× control): Hold infusion for 1 hour, then decrease by 3 units/kg/hour 1, 2

Subcutaneous Administration

Fixed-Dose Weight-Adjusted Regimen

For patients without IV access or for outpatient treatment 1, 3, 6:

• Loading dose: 333 units/kg subcutaneously 1, 3, 6
• Maintenance dose: 250 units/kg subcutaneously every 12 hours 1, 3, 6
• This regimen is as effective and safe as low-molecular-weight heparin and does not require aPTT monitoring 6, 7
• Administer deep subcutaneously (above iliac crest or in abdominal fat layer) using a 25-26 gauge needle 3

Alternative Monitored Subcutaneous Regimen

If aPTT monitoring is desired 3:

• Initial dose: 5000 units IV, followed by 10,000-20,000 units subcutaneously 3
• Maintenance: 15,000-20,000 units every 12 hours or 8,000-10,000 units every 8 hours 3
• Check aPTT 4-6 hours after injection 3

Special Populations

Severe Renal Insufficiency (CrCl <30 mL/min)

• UFH is the preferred anticoagulant as it undergoes hepatic metabolism rather than renal clearance 2, 5
• Use standard weight-based IV dosing with aPTT monitoring 2, 5

Pediatric Patients

• Use preservative-free formulations in neonates and infants 3
• Loading dose: 75-100 units/kg IV bolus over 10 minutes 3
• Maintenance infusion: 3
  • Infants <2 months: 25-30 units/kg/hour (highest requirements)
  • Children >1 year: 18-20 units/kg/hour
• Target aPTT: 60-85 seconds (corresponding to anti-factor Xa 0.35-0.70 IU/mL) 3

Cardiac Patients and STEMI with Fibrinolytics

• Reduced dosing: 60-70 units/kg bolus (maximum 4000 units) followed by 12-15 units/kg/hour infusion (maximum 1000 units/hour) 1, 5
• This lower dose minimizes bleeding risk when combined with thrombolytic therapy 5

Critical Pitfalls to Avoid

Dosing Errors

• Never confuse heparin vial strengths—confirm the correct concentration before administration, as 1 mL vials can be confused with catheter lock flush vials 3
• Do not exceed maximum doses: Cap bolus at 4000-5000 units and infusion at 1000 units/hour in adults to minimize bleeding risk 5, 3
• Avoid intramuscular administration due to high risk of hematoma formation 3

Monitoring Issues

• Different aPTT reagents have variable heparin responsiveness—ensure your institution has validated the therapeutic aPTT range against anti-factor Xa levels 2
• Warfarin directly prolongs aPTT by approximately 20 seconds for each 1.0 increase in INR, which can lead to inappropriate dose reductions when transitioning to warfarin 8
• Do not adjust UFH dose on day 1 in response to a single subtherapeutic aPTT if using subcutaneous administration, as this leads to excessive supratherapeutic values on subsequent days 8

Contraindications

• Absolute contraindication: Active heparin-induced thrombocytopenia (HIT) 2, 5
• Use alternative anticoagulants (argatroban, fondaparinux, or direct thrombin inhibitors) in patients with history of HIT 1, 2, 5

Duration and Transition to Oral Anticoagulation

• Minimum duration: Continue UFH for at least 5 days and until INR ≥2.0 for at least 24 hours when transitioning to warfarin 1, 3
• Overlap warfarin with UFH from day 1—do not wait for therapeutic aPTT before starting warfarin 1, 3
• For non-warfarin oral anticoagulants: Stop IV UFH immediately after first dose of oral agent, or give oral agent 0-2 hours before next scheduled intermittent UFH dose 3