What is the relationship between Activated Partial Thromboplastin Time (APTT) and heparin infusion?

From the Guidelines

Monitoring the activated partial thromboplastin time (APTT) is essential when managing a heparin drip, with a target APTT range of 1.5-2.5 times the patient's baseline or the laboratory control value, which usually corresponds to 60-80 seconds, as recommended by the 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-st-elevation myocardial infarction 1.

Key Considerations

• When initiating a heparin drip, start with a loading dose of 80 units/kg IV bolus, followed by a continuous infusion at 18 units/kg/hour.
• Check the APTT 6 hours after starting therapy and adjust the infusion rate according to a standardized protocol.
• If the APTT is below the target range, give an additional bolus of 40 units/kg and increase the infusion rate by 2-4 units/kg/hour.
• If the APTT is above the target range, hold the infusion for 1 hour and decrease the rate by 2-3 units/kg/hour.

Importance of Monitoring

• APTT monitoring is crucial because heparin has a narrow therapeutic window—too little risks thrombosis while too much increases bleeding risk.
• Individual patient factors like weight, renal function, and concomitant medications can affect heparin metabolism, necessitating personalized dose adjustments based on APTT results.

Clinical Guidelines

• The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) recommends monitoring APTT values in the target range (e.g., for a control aPTT of 30 s, the target range [1.5 to 2.5 times control] would be 45 to 75 s) 1.
• The American Heart Association (AHA) also provides guidelines for heparin dose adjustment, including a protocol for adjusting the infusion rate based on APTT results 1.

From the FDA Drug Label

1. 2 Pharmacodynamics Various times (activated clotting time, activated partial thromboplastin time, prothrombin time, whole blood clotting time) are prolonged by full therapeutic doses of heparin; in most cases, they are not measurably affected by low doses of heparin. Specific Populations Geriatric patients Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial thromboplastin times (aPTTs) compared with patients under 60 years of age [see Use in Specific Populations (8.5)].

The activated partial thromboplastin time (aPTT) is prolonged by full therapeutic doses of heparin. In patients over 60 years of age, similar doses of heparin may result in higher plasma levels of heparin and longer aPTT times compared to patients under 60 years of age 2.

• Key points:
  • Heparin prolongs aPTT.
  • Geriatric patients may have longer aPTT times compared to younger patients.
• Clinical decision: Monitor aPTT closely in patients receiving heparin, especially in geriatric patients, to adjust the dose and prevent bleeding complications 2.

From the Research

APTT and Heparin Drip

• The activated partial thromboplastin time (aPTT) is used to monitor unfractionated heparin (UFH) therapy, but variability in aPTT reagents necessitates site-specific validation of the aPTT therapeutic range 3.
• In patients with apparent heparin resistance, anti-factor Xa monitoring may be superior to measurement of aPTT 3.
• Low-molecular-weight heparin (LMWH) has more predictable pharmacokinetic and pharmacodynamic properties than UFH and has replaced UFH for most clinical indications 3.
• The use of direct oral anticoagulants (DOACs) is being explored as an alternative to heparin and LMWH for anticoagulation therapy, with some studies suggesting that DOACs may be more effective and have a similar safety profile to LMWH 4, 5, 6.

Heparin Drip Management

• UFH infusion is preferable to LMWH injection in patients with creatinine clearance of < 25 mL/min, until further data on therapeutic dosing of LMWHs in renal failure have been published 3.
• Protamine may help to reverse bleeding related to LMWH, although anti-factor Xa activity is not fully normalized by protamine 3.
• The management of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) is complex and may involve the use of alternative anticoagulants such as argatroban, fondaparinux, or bivalirudin 7.

Comparison of Anticoagulants

• DOACs have been shown to be more effective than LMWH in preventing venous thromboembolism (VTE) in patients with cancer, with a comparable safety profile 6.
• A network meta-analysis of randomized trials found that DOACs and LMWH reduced symptomatic VTE compared with no active treatment, but increased the risk of major bleeding 5.
• The choice of anticoagulant depends on various factors, including the patient's renal function, weight, and underlying medical conditions, as well as the specific clinical indication for anticoagulation therapy 3, 4, 5, 6.