Heparin Dosing: 60 units/kg Bolus and 12 units/kg/hr Infusion
The 60 units/kg bolus (maximum 4000 units) followed by 12 units/kg/hr infusion (maximum 1000 units/hr) is the appropriate dosing regimen for acute coronary syndromes (ACS) including ST-elevation myocardial infarction with fibrinolytic therapy and non-ST-elevation MI/unstable angina, but this dosing is inadequate for venous thromboembolism (VTE), which requires higher dosing of 80 units/kg bolus followed by 18 units/kg/hr. 1, 2
Indication-Specific Dosing
For Acute Coronary Syndromes (STEMI with Fibrinolytics, NSTEMI/Unstable Angina)
Use 60 units/kg IV bolus (maximum 4000 units) followed by 12 units/kg/hr infusion (maximum 1000 units/hr) for patients with ST-elevation myocardial infarction receiving fibrinolytic therapy (alteplase, reteplase, or tenecteplase). 1
The European Society of Cardiology recommends the same dosing: 60 units/kg bolus (maximum 4000 units) followed by 12 units/kg/hr infusion (maximum 1000 units/hr) for 24-48 hours when used with fibrinolytic therapy. 1
For NSTEMI/unstable angina without fibrinolytics, guidelines recommend 60-70 units/kg bolus (maximum 5000 units) followed by 12-15 units/kg/hr infusion. 1, 2
Target aPTT is 1.5-2.0 times control (approximately 50-70 seconds), with monitoring at 3,6,12, and 24 hours. 1
For Venous Thromboembolism (DVT/PE)
Do NOT use the 60/12 dosing for VTE—this is a critical error. The American College of Chest Physicians recommends 80 units/kg IV bolus followed by 18 units/kg/hr infusion for treatment of deep vein thrombosis and pulmonary embolism. 3, 2
Using the lower ACS dosing (60 units/kg and 12 units/kg/hr) for VTE has been associated with higher recurrence rates in randomized trials. 2
Target aPTT for VTE is 1.5-2.5 times control (approximately 45-75 seconds), and achieving therapeutic levels within 24 hours is critical for reducing mortality in pulmonary embolism. 3, 2
The FDA label for general therapeutic anticoagulation lists a continuous infusion option of 20,000-40,000 units/24 hours, which translates to approximately 14-28 units/kg/hr for a 68 kg patient. 4
Evidence Supporting the 60/12 Dosing for ACS
Guideline Evolution and Rationale
The 1999 ACC/AHA guidelines revised their recommendation from 70 units/kg bolus and 15 units/kg/hr down to 60 units/kg bolus (maximum 4000 units) and 12 units/kg/hr (maximum 1000 units/hr) specifically for patients receiving fibrinolytic therapy. 1
This lower dosing was adopted because trials demonstrated an association between high aPTT values and increased bleeding, intracranial hemorrhage, reinfarction, and death in ACS patients treated with heparin. 5
Research showed that traditional non-weight-adjusted dosing (5000 unit bolus/1000 units/hr) resulted in marked initial overanticoagulation in 95% of patients at 6 hours, placing them at higher risk of adverse outcomes. 5
The 60/12 regimen achieved target aPTT range (45-70 seconds) in 34% of patients at 6 hours compared to 0-5% with other regimens, and required fewer infusion changes. 5
Weight-Based Dosing Considerations
Maximum Dose Caps Are Essential for ACS
Always apply the maximum dose caps for ACS patients: 4000 units maximum bolus and 1000 units/hr maximum infusion rate for patients weighing >70 kg. 1, 2
These caps reduce bleeding risk without compromising efficacy in ACS patients. 1
Obesity and Dosing Challenges
Obese patients are particularly prone to subtherapeutic anticoagulation with standard dosing, with delays in achieving therapeutic aPTT being most evident in this population. 6
Recent research suggests that higher maximum doses (10,000 units bolus and 2250 units/hr infusion) achieve therapeutic anticoagulation more rapidly in both obese and nonobese patients without increased bleeding. 6
However, even with higher doses, only 23% of patients achieved therapeutic aPTT within 6 hours, suggesting that current dosing may still be inadequate for some patients. 6
Monitoring and Dose Adjustments
Initial Monitoring Protocol
Check baseline aPTT, INR, and platelet count before initiating therapy. 4
For continuous IV infusion, check aPTT at 4-6 hours after bolus, then approximately every 4 hours until stable, then daily. 4
For ACS with fibrinolytics, monitor at 3,6,12, and 24 hours. 1
Standardized Dose Adjustment Protocol
For aPTT <35 seconds (<1.2 times control): Give 80 units/kg bolus and increase infusion by 4 units/kg/hr. 3
For aPTT 35-45 seconds (1.2-1.5 times control): Give 40 units/kg bolus and increase infusion by 2 units/kg/hr. 3
For aPTT 46-70 seconds (1.5-2.3 times control): No change needed. 3
For aPTT 71-90 seconds (2.3-3.0 times control): Reduce infusion by 2 units/kg/hr. 3
For aPTT >90 seconds (>3.0 times control): Stop infusion for 1 hour, then reduce infusion by 3 units/kg/hr. 3
Ongoing Safety Monitoring
Monitor platelet counts daily to detect heparin-induced thrombocytopenia. 1, 4
Periodically monitor hematocrit and occult blood in stool throughout therapy. 4
Duration of Therapy
For ACS
Continue heparin for 48 hours in patients receiving fibrinolytic therapy. 1
Continuation beyond 48 hours should be restricted to patients at high risk for systemic or venous thromboembolism. 1
For VTE
Continue heparin for at least 5 days with overlap with warfarin for at least 4-5 days. 3
Discontinue heparin when INR is ≥2.0 for at least 24 hours. 3
Common Pitfalls to Avoid
Critical Dosing Errors
Never use ACS dosing (60/12) for VTE patients—this leads to subtherapeutic anticoagulation and increased recurrence rates. 2
Never exceed maximum bolus (4000-5000 units) or infusion rates (1000 units/hr) in ACS patients—this increases bleeding risk without additional benefit. 1, 2
Using fixed-dose regimens instead of weight-based dosing leads to subtherapeutic anticoagulation in many patients and excessive anticoagulation in others. 2, 5
Monitoring Failures
Failure to achieve therapeutic aPTT within 24 hours is associated with higher mortality in pulmonary embolism patients. 3, 2
Inadequate monitoring of aPTT can lead to either subtherapeutic anticoagulation (increasing thrombosis risk) or excessive anticoagulation (increasing bleeding risk). 3, 2
Not checking daily platelet counts can result in missed diagnosis of heparin-induced thrombocytopenia. 1, 4
Transition Errors
Discontinuing heparin before warfarin has reached therapeutic INR levels (≥2.0 for at least 24 hours) can lead to treatment failure. 3
For warfarin transition, continue full heparin therapy for several days until INR has reached a stable therapeutic range; do not taper heparin. 4
Special Populations
Patients with Renal Dysfunction
- Consider dose reduction in patients with significant renal dysfunction (serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women), though specific adjustments are not well-defined for unfractionated heparin. 1
Patients Receiving Glycoprotein IIb/IIIa Inhibitors
- When GP IIb/IIIa inhibitors are used during PCI, reduce heparin dosing to 50-60 units/kg bolus with target ACT of 200 seconds. 1, 7