What is the standard protocol for heparin therapy, including dosing and reversal?

Heparin Protocol for Therapeutic Anticoagulation

For therapeutic anticoagulation, administer an initial IV bolus of 80 units/kg followed by continuous infusion at 18 units/kg/hour, with aPTT monitoring at 6 hours and dose adjustments to maintain aPTT at 1.5-2.5 times control value. 1

Initial Dosing Regimen

Intravenous Route (Preferred)

• Bolus dose: 80 units/kg IV push 1
• Continuous infusion: 18 units/kg/hour (approximately 20,000-40,000 units per 24 hours for average adult) 2, 3
• Alternative FDA-approved regimen: 5,000 unit bolus followed by 32,000 units per 24 hours continuous infusion 3

Subcutaneous Route (When IV Access Unavailable)

• Loading dose: 333 units/kg subcutaneously 1, 4
• Maintenance dose: 250 units/kg every 12 hours 1, 4
• This fixed-dose subcutaneous regimen is as effective as LMWH and suitable for outpatient treatment 4

Monitoring Protocol

aPTT Monitoring Schedule

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

Dose Adjustment Nomogram

Use the following weight-based adjustments 1:

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

Additional Monitoring

• Platelet count: Monitor periodically throughout therapy to detect heparin-induced thrombocytopenia 1, 3
• Hematocrit and occult blood: Check during entire treatment course 3

Duration of Therapy

• Standard duration: 5-10 days for venous thromboembolism 2, 5
• Overlap with warfarin: Continue full-dose heparin for at least 5 days AND until INR ≥ 2.0 for 2 consecutive days 2
• Recent evidence supports 4-5 days as adequate for submassive thrombosis, though 7-10 days remains standard for extensive proximal DVT 5

Special Populations

Severe Renal Failure (CrCl < 25-30 mL/min)

• Preferred anticoagulant: Unfractionated heparin over LMWH due to hepatic metabolism 2, 1
• Monitor with anti-Xa activity if available 2

Morbidly Obese Patients

• Dosing weight calculation: Use adjusted body weight = IBW + 0.3(ABW - IBW) or IBW + 0.4(ABW - IBW) 6
• Standard protocols with maximum dose caps cause significant delays in achieving therapeutic anticoagulation 6
• Do not cap initial bolus or infusion rates based on absolute units 6

Pediatric Patients

• Use preservative-free formulation in neonates and infants 3
• Initial dose: 75-100 units/kg IV bolus over 10 minutes 3
• Maintenance: Infants require 25-30 units/kg/hour (highest requirements in those < 2 months at average 28 units/kg/hour) 3
• Children > 1 year: 18-20 units/kg/hour 3
• Target aPTT: 60-85 seconds (reflecting anti-Factor Xa 0.35-0.70 U/mL) 3

Cardiovascular Surgery

• Total body perfusion: Minimum 150 units/kg, typically 300 units/kg for procedures < 60 minutes or 400 units/kg for longer procedures 3

Heparin Reversal

Protamine Sulfate Dosing

• Dose: 1 mg protamine neutralizes approximately 100 units of heparin 3
• Maximum rate: No more than 50 mg over any 10-minute period 3
• Time-dependent dosing: Reduce protamine dose based on time since last heparin dose, as heparin has half-life of approximately 30 minutes IV 3
• Critical warning: Protamine can cause anaphylactoid reactions; have resuscitation equipment immediately available 3

Important Clinical Pitfalls

Reagent Variability

• Different aPTT reagents have vastly different responsiveness to heparin 2, 1
• The therapeutic range must be calibrated to your specific laboratory's reagent 2
• A therapeutic range of 60-85 seconds corresponds to plasma heparin 0.2-0.4 U/mL by protamine titration or 0.35-0.7 U/mL anti-Factor Xa 2

Nonlinear Pharmacokinetics

• Heparin clearance is dose-dependent and saturable at therapeutic doses 2
• Both intensity and duration of effect rise disproportionately with increasing doses 2
• This explains variable patient responses and the phenomenon of "heparin resistance" 2

Heparin-Induced Thrombocytopenia (HIT)

• Absolute contraindication to continued heparin use 1
• Switch to alternative anticoagulants: argatroban, danaparoid, or fondaparinux 1

Drug Interactions

• Reduce heparin dose by 50% when used with glycoprotein IIb/IIIa inhibitors (initial bolus 50 units/kg) 2
• Modify dosing when combined with thrombolytics 2
• Post-thrombolysis regimen: 5,000 unit bolus followed by 24,000 units per 24 hours 2

Route-Specific Considerations

• Subcutaneous administration has delayed onset (1-2 hours) and requires higher initial doses due to lower bioavailability 2
• Never use intramuscular route due to high risk of hematoma formation 3
• Deep subcutaneous injection should be in intrafat layer (above iliac crest or abdominal fat) using 25-26 gauge needle 3