What is the recommended heparin infusion protocol, including loading dose and follow-up adjustments?

Heparin Infusion Protocol with Loading and Follow-Up

Initial Loading and Infusion Dosing

For venous thromboembolism (VTE) treatment, administer an initial IV bolus of 80 units/kg followed by a continuous infusion of 18 units/kg/hour, with the first aPTT check at 6 hours and dose adjustments targeting an aPTT of 1.5-2.5 times control (typically 60-85 seconds). 1, 2, 3, 4

Weight-Based Protocol (Preferred)

• Loading dose: 80 units/kg IV bolus 1, 2, 5, 6
• Initial infusion: 18 units/kg/hour continuous IV 1, 2, 4, 5
• This weight-based approach achieves therapeutic anticoagulation significantly faster than fixed-dose regimens, with 97% of patients reaching therapeutic range within 24 hours compared to only 77% with standard dosing 6

Fixed-Dose Alternative (When Weight Unavailable)

• Loading dose: 5,000 units IV bolus 1, 5
• Initial infusion: At least 32,000 units per 24 hours (approximately 1,333 units/hour) 1
• This approach is less reliable and associated with higher recurrence rates 1, 6

Monitoring Protocol

First aPTT Check

• Obtain first aPTT 6 hours after the initial bolus dose 1, 4, 5
• Target therapeutic range: aPTT 1.5-2.5 times control value (typically 60-85 seconds or 46-70 seconds depending on laboratory) 1, 3, 4, 5
• This corresponds to plasma heparin levels of 0.35-0.7 units/mL anti-factor Xa activity 3, 4

Subsequent Monitoring

• Check aPTT approximately every 4-6 hours after each dose adjustment until stable in therapeutic range 4, 5
• Once therapeutic and stable, check aPTT daily 4, 5
• Monitor platelet counts periodically throughout therapy to detect heparin-induced thrombocytopenia 4, 5

Dose Adjustment Nomogram

Use this standardized protocol for all aPTT-based adjustments: 1, 3, 4

aPTT < 35 seconds (< 1.2 times control)

• Give 80 units/kg IV bolus 1, 3, 4
• Increase infusion rate by 4 units/kg/hour 1, 3, 4
• Recheck aPTT in 6 hours 1

aPTT 35-45 seconds (1.2-1.5 times control)

• Give 40 units/kg IV bolus 1, 3, 4
• Increase infusion rate by 2 units/kg/hour 1, 3, 4
• Recheck aPTT in 6 hours 1

aPTT 46-70 seconds (1.5-2.3 times control) - THERAPEUTIC RANGE

• No change needed 1, 3, 4
• Recheck aPTT next morning or in 24 hours 1

aPTT 71-90 seconds (2.3-3.0 times control)

• Decrease infusion rate by 2 units/kg/hour 1, 3, 4
• Recheck aPTT in 6 hours 1

aPTT > 90 seconds (> 3.0 times control)

• Stop infusion for 1 hour 1, 3, 4
• Decrease infusion rate by 3 units/kg/hour 1, 3, 4
• Recheck aPTT in 6 hours 1

Duration and Transition to Oral Anticoagulation

• Continue heparin for at least 5 days with overlap with warfarin for at least 4-5 days 1, 2, 7
• Discontinue heparin only when INR ≥ 2.0 for at least 24 hours 1, 2, 5
• Do not taper heparin when discontinuing 5

Special Clinical Contexts

Acute Coronary Syndromes (Lower Doses Required)

• Unstable angina/NSTEMI: 60-70 units/kg bolus (maximum 5,000 units), then 12-15 units/kg/hour infusion (maximum 1,000 units/hour) 1, 3
• STEMI with fibrinolytics: 60 units/kg bolus (maximum 4,000 units), then 12 units/kg/hour (maximum 1,000 units/hour) 1
• Target aPTT: 50-70 seconds for 24-48 hours 1

Morbidly Obese Patients

• Standard weight-based protocols may significantly delay therapeutic anticoagulation in patients with extreme obesity 8
• Consider using adjusted body weight: IBW + 0.3(ABW - IBW) or IBW + 0.4(ABW - IBW) 8
• Do not cap maximum initial doses in morbidly obese patients 8

Pediatric Dosing

• Use preservative-free heparin in neonates and infants 5
• Loading dose: 75-100 units/kg IV bolus over 10 minutes 5
• Maintenance infusion: 2, 5
  • Infants < 1 year: 28 units/kg/hour
  • Children 1-15 years: 20 units/kg/hour
  • Adolescents ≥ 15 years: 18 units/kg/hour
• Target aPTT: 60-85 seconds 3, 5

Critical Pitfalls to Avoid

Subtherapeutic Anticoagulation

• Failure to achieve therapeutic aPTT within 24 hours is associated with dramatically increased mortality in pulmonary embolism patients 1, 2
• Patients with aPTT < 50 seconds have a 15-fold increased risk of recurrent VTE 1, 3
• Even aPTT values of 50-59 seconds carry significantly elevated thrombotic risk 3
• Weight-based dosing reduces recurrent thromboembolism by 80% compared to fixed dosing (relative risk 5.0 with standard care) 6

Excessive Anticoagulation

• aPTT > 90 seconds increases bleeding risk without additional antithrombotic benefit 3
• The heparin-antithrombin complex cannot inactivate fibrin-bound thrombin, so supratherapeutic levels provide no advantage 1

Monitoring Errors

• Do not check first aPTT before 6 hours—heparin has nonlinear pharmacokinetics with dose-dependent clearance 1
• Different aPTT reagents have variable responsiveness to heparin; therapeutic ranges must be laboratory-specific 1, 3

Premature Discontinuation

• Never stop heparin before warfarin reaches therapeutic INR for at least 24 hours—this creates a prothrombotic gap 1, 2, 5

Drug Interactions

• Dosing must be modified when heparin is combined with thrombolytics or GP IIb/IIIa inhibitors 1, 3
• These combinations significantly increase bleeding risk 1

Heparin Resistance

• If therapeutic aPTT cannot be achieved despite high doses, consider switching to anti-factor Xa monitoring with target range 0.35-0.7 units/mL 3, 4
• Heparin resistance results from AT-independent binding to plasma proteins and variable clearance mechanisms 1