What is the initial dosing regimen for unfractionated heparin in an adult patient requiring anticoagulation, considering factors such as renal function and risk of bleeding?

Unfractionated Heparin Dosing for Therapeutic Anticoagulation

For therapeutic anticoagulation in adults, administer unfractionated heparin as an 80 units/kg IV bolus followed by 18 units/kg/hour continuous infusion, with aPTT monitoring at 6 hours and dose adjustments to maintain aPTT at 1.5-2.5 times control (approximately 50-70 seconds). 1, 2, 3

Initial Dosing Regimen

Intravenous Administration (Preferred Route)

• Bolus dose: 80 units/kg IV (maximum 4,000 units for patients >70 kg) 1, 3
• Continuous infusion: 18 units/kg/hour (maximum 1,000 units/hour for patients >70 kg) 1, 2, 3
• This weight-based approach achieves therapeutic anticoagulation in 97% of patients within 24 hours, compared to only 77% with fixed-dose regimens 4

Subcutaneous Administration (Alternative)

• Loading dose: 333 units/kg subcutaneously 1, 3
• Maintenance dose: 250 units/kg every 12 hours 1, 3
• This regimen does not require aPTT monitoring and is as effective as LMWH for venous thromboembolism treatment 5
• Administer deep subcutaneously (above iliac crest or abdominal fat layer) with a 25-26 gauge needle 3

Monitoring Protocol

Laboratory Testing Schedule

• First aPTT: Obtain 6 hours after initiating therapy 2, 3
• Subsequent monitoring: Every 4-6 hours until stable in therapeutic range, then daily 2, 3
• Target aPTT: 1.5-2.5 times control value (approximately 50-70 seconds), corresponding to anti-Factor Xa levels of 0.3-0.7 IU/mL 1, 2

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

Additional Monitoring Requirements

• Platelet counts: Monitor daily throughout therapy to detect heparin-induced thrombocytopenia 1, 3
• Hematocrit and occult blood: Monitor periodically regardless of administration route 3

Special Considerations Based on Patient Factors

Renal Impairment

• UFH is the preferred anticoagulant for severe renal dysfunction (CrCl <30 mL/min) as it is primarily metabolized by the liver, not renally excreted 1, 2
• LMWH and fondaparinux are contraindicated when CrCl <30 mL/min due to accumulation risk 1

Bleeding Risk Assessment

• High bleeding risk patients: Consider using the lower end of dosing ranges or subcutaneous administration for easier reversal 3
• UFH has the advantage of short half-life (60-90 minutes) and reversibility with protamine sulfate 6
• Avoid intramuscular administration due to high risk of hematoma formation 3

Obesity and Weight Extremes

• Patients >70 kg: Cap initial bolus at 4,000 units and infusion at 1,000 units/hour to prevent excessive anticoagulation 1, 3
• Weight-based dosing is critical as fixed-dose regimens result in subtherapeutic anticoagulation in most patients 4

Pediatric Dosing

• Use preservative-free formulations in neonates and infants 2, 3
• Initial bolus: 75-100 units/kg IV over 10 minutes 3
• Maintenance infusion:
  • Infants <2 months: 28 units/kg/hour (highest requirements) 3
  • Infants: 25-30 units/kg/hour 3
  • Children >1 year: 18-20 units/kg/hour 3
• Target aPTT: 60-85 seconds (corresponding to anti-Factor Xa 0.35-0.70 IU/mL) 3

Common Pitfalls and How to Avoid Them

Critical Errors to Prevent

• Vial confusion: Always confirm you are using the correct concentration vial, not a catheter lock flush vial 3
• Fixed dosing: Never use fixed-dose regimens (e.g., 5,000 unit bolus, 1,000 units/hour); these achieve therapeutic levels in <80% of patients 4
• Delayed monitoring: Failure to check aPTT at 6 hours leads to prolonged subtherapeutic anticoagulation 2

Laboratory Considerations

• aPTT reagent variability: Different aPTT reagents have variable responsiveness to heparin; ensure your institution has validated the therapeutic range for your specific reagent 2, 7
• Anti-Xa assays: While often considered superior, significant differences exist between anti-Xa assay types; standardization remains problematic 7
• Antithrombin levels: While low antithrombin may theoretically reduce UFH efficacy, routine measurement is not recommended as clinical significance remains unclear 7

Clinical Management Issues

• "Heparin resistance": This concept lacks supporting data; if aPTT remains subtherapeutic despite high doses, verify proper administration, check for laboratory error, and consider anti-Xa monitoring rather than assuming resistance 7
• Supratherapeutic dosing: Increases bleeding risk significantly; strict adherence to weight-based nomograms and monitoring protocols is essential 8
• Premature discontinuation: Continue UFH for minimum 5 days when bridging to warfarin, until INR is ≥2.0 for at least 24 hours 1, 3

Specific Clinical Scenarios

Acute Coronary Syndromes with Fibrinolytics

• With alteplase, reteplase, or tenecteplase: Use 60 units/kg bolus (max 4,000 units) followed by 12 units/kg/hour infusion (max 1,000 units/hour) 1
• With streptokinase: Delay heparin for 4 hours post-thrombolysis, then start when aPTT <2× control 1

Cardiovascular Surgery

• Total body perfusion: Minimum 150 units/kg; use 300 units/kg for procedures <60 minutes or 400 units/kg for procedures >60 minutes 3

VTE Prophylaxis (Low-Dose)

• Postoperative prophylaxis: 5,000 units subcutaneously 2 hours before surgery, then 5,000 units every 8-12 hours for 7 days or until fully ambulatory 1, 3
• Medical patients: 5,000 units subcutaneously every 8 hours 1