What is the recommended dosing for therapeutic anticoagulation with heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH))?

Therapeutic Anticoagulation with Heparin

Unfractionated Heparin (UFH) Dosing

For therapeutic anticoagulation with unfractionated heparin, initiate with an 80 units/kg IV bolus (maximum 4000 units) followed by a continuous infusion of 18 units/kg/hour (maximum 1000 units/hour), adjusting to maintain aPTT at 1.5-2.5 times control (approximately 50-70 seconds). 1, 2

Intravenous Administration

• Initial bolus: 80 units/kg IV (maximum 4000 units for patients >50 kg) 1, 2
• Continuous infusion: 18 units/kg/hour (maximum 1000 units/hour for patients >55 kg) 1, 2
• Target aPTT: 1.5-2.5 times control value (approximately 50-70 seconds) 1, 2
• Alternative target: Anti-factor Xa level of 0.3-0.7 IU/mL 1, 3

Subcutaneous Administration (when IV access unavailable)

• Loading dose: 333 units/kg subcutaneously 1, 2
• Maintenance dose: 250 units/kg subcutaneously every 12 hours 1, 2
• Administer deep subcutaneously (intrafat) above the iliac crest or in abdominal fat layer 2

Monitoring Protocol

The first aPTT measurement should be obtained 6 hours after initiating therapy, then approximately every 4-6 hours until stable in therapeutic range, followed by daily monitoring. 3, 2

• Baseline labs: CBC with platelet count, aPTT, PT/INR, renal and hepatic function 1, 2
• First aPTT check: 6 hours after bolus dose 3, 2
• Subsequent monitoring: Every 4-6 hours until therapeutic, then daily 3, 2
• Platelet monitoring: Every 2-3 days for first 14 days, then every 2 weeks or as clinically indicated 1, 2

Dose Adjustment Nomogram

Adjust infusion rate based on aPTT results using the following standardized approach 3:

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

Low Molecular Weight Heparin (LMWH) Dosing

LMWH is preferred over UFH for most VTE treatment due to superior efficacy, safety profile, and convenience. 1

Enoxaparin

• Standard dosing: 1 mg/kg subcutaneously every 12 hours 1
• Alternative: 1.5 mg/kg subcutaneously once daily 1
• Renal adjustment: If CrCl <30 mL/min, reduce to 1 mg/kg once daily 1
• Obesity consideration: 0.8 mg/kg every 12 hours if BMI ≥40 kg/m² 1

Dalteparin

• Acute treatment: 200 units/kg subcutaneously once daily 1
• Extended treatment: 150 units/kg once daily after first 30 days 1
• Alternative: 100 units/kg subcutaneously every 12 hours 1

LMWH Monitoring

Routine monitoring is not required for LMWH at standard doses. 1, 4

• Anti-Xa monitoring indicated for: Pregnancy, pediatrics, severe renal dysfunction (CrCl <30 mL/min), obesity (BMI >40), or high bleeding risk 1, 4
• Target anti-Xa levels: 0.5-1.1 IU/mL (4 hours post-dose for twice daily dosing) or 1.0-2.0 IU/mL (4 hours post-dose for once daily dosing) 1, 4

Special Populations

Renal Insufficiency

UFH is preferred over LMWH in patients with severe renal dysfunction (CrCl <30 mL/min) because it is primarily metabolized by the liver rather than renally cleared. 1, 3

• LMWH is contraindicated if CrCl <30 mL/min 1
• If enoxaparin must be used with CrCl <30 mL/min, reduce to 1 mg/kg once daily 1

Pediatric Dosing

• Initial bolus: 75-100 units/kg IV over 10 minutes 2
• Infants <2 months: 25-30 units/kg/hour (average 28 units/kg/hour) 2
• Children >1 year: 18-20 units/kg/hour 2
• Target aPTT: 60-85 seconds (corresponding to anti-factor Xa 0.35-0.70 IU/mL) 2

Cancer Patients

LMWH is preferred over UFH for cancer-associated VTE due to superior efficacy in preventing recurrent thrombosis. 1

• Dalteparin 200 units/kg daily for 30 days, then 150 units/kg daily is the only FDA-approved LMWH regimen for cancer-associated VTE 1
• Continue anticoagulation as long as active malignancy persists 1

Common Pitfalls and Caveats

Underdosing in Obesity

Obese patients frequently receive inadequate heparin doses, leading to delayed therapeutic anticoagulation and increased risk of recurrent thrombosis. 5

• Use actual body weight for dosing calculations, not ideal body weight 5
• Do not cap doses arbitrarily in obese patients—the 4000 unit bolus cap and 1000 units/hour infusion cap apply only to patients >50-55 kg per standard protocols 2
• Each 1 unit/kg/hour decrease below recommended dosing delays therapeutic anticoagulation by 0.75-1.5 hours 5

Heparin-Induced Thrombocytopenia (HIT)

Monitor platelet counts throughout heparin therapy, as HIT occurs in approximately 1-3% of UFH-treated patients but is 10-fold less common with LMWH. 1, 4

• If HIT develops, immediately discontinue all heparin products and switch to alternative anticoagulants (bivalirudin, fondaparinux, or argatroban) 3
• UFH carries higher HIT risk than LMWH 4

Laboratory Variability

Different aPTT reagents have variable responsiveness to heparin, requiring institution-specific therapeutic ranges to be validated. 1, 3

• The aPTT ratio of 1.5-2.5 should correspond to anti-factor Xa levels of 0.3-0.7 IU/mL 1, 3
• Validate your institution's aPTT assay against anti-Xa levels 1
• Disagreements between aPTT and anti-Xa assays occur in individual cases 4

Nonlinear Pharmacokinetics

Heparin exhibits dose-dependent, saturable clearance, making the anticoagulant response nonlinear at therapeutic doses. 1, 3

• Both intensity and duration of effect increase disproportionately with dose 1, 3
• This necessitates frequent monitoring and dose adjustments, particularly during initiation 1, 3

Bleeding Risk

Heparin increases bleeding risk through both anticoagulant effects and direct effects on platelet function and vessel wall permeability. 1

• Monitor hemoglobin, hematocrit, and occult blood in stool throughout therapy 2
• Avoid intramuscular injections due to high risk of hematoma formation 2