What is the therapeutic range for Heparin (unfractionated heparin) and the protocol for transitioning from intravenous infusion to subcutaneous dosing?

From the Guidelines

Heparin dosing typically begins with a weight-based bolus of 80 units/kg (maximum 10,000 units) followed by a continuous infusion starting at 18 units/kg/hour (maximum 2,000 units/hour) as recommended by the most recent guidelines 1. The therapeutic range for unfractionated heparin is an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the control value, or an anti-Xa level of 0.3-0.7 units/mL. Some key points to consider when administering heparin include:

• Dose adjustments are made according to institutional nomograms, with aPTT typically checked 6 hours after initiation and 6 hours after any dose change.
• When transitioning from intravenous to subcutaneous heparin, discontinue the infusion and administer the first subcutaneous dose (typically 15,000-20,000 units divided into 2-3 daily injections) 1 hour before stopping the infusion to maintain anticoagulation.
• Subcutaneous dosing is usually 250-300 units/kg every 12 hours, with dose adjustments based on mid-interval aPTT values drawn 6 hours after injection.
• This transition is necessary when patients are stabilized but still require anticoagulation.
• Heparin works by binding to antithrombin, enhancing its ability to inhibit thrombin and factor Xa, thereby preventing clot formation and extension.
• Careful monitoring is essential due to heparin's narrow therapeutic window and the risk of bleeding complications, as highlighted in studies such as 1 and 1. It's also important to note that the therapeutic aPTT range may vary depending on the reagents and equipment used, and should be adapted to the local laboratory's standards, as discussed in 1.

From the FDA Drug Label

The dosing recommendations in Table 1 are based on clinical experience be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage schedules may be used as guidelines: Table 1: Recommended Adult Full-Dose Heparin Regimens for Therapeutic Anticoagulant Effect *Based on 68 kg patient METHOD OF ADMINISTRATION | FREQUENCY | RECOMMENDED DOSE Deep Subcutaneous (Intrafat) Injection | Use a different site for each injection to prevent the development of hematoma | Initial Dose 5,000 units by intravenous injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously | Every 8 hours or 8,000 to 10,000 units of a concentrated solution | Every 12 hours 15,000 to 20,000 units of a concentrated solution Intermittent Intravenous Injection | Initial Dose 10,000 units, either undiluted or in 50 to 100 mL of 0. 9% Sodium Chloride Injection, USP | Every 4 to 6 hours 5,000 to 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP Continuous Intravenous Infusion | Initial Dose 5,000 units by intravenous injection | Continuous 20,000 to 40,000 units/24 hours in 1,000 mL of 0.9% Sodium Chloride Injection, USP (or in any compatible solution) for infusion Dosage is considered adequate when the activated partial thromboplastin time (aPTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2. 5 to 3 times the control value.

The therapeutic range for heparin is when the activated partial thromboplastin time (aPTT) is 1.5 to 2 times normal. To switch from infusion to subcutaneous dosing, the following guidelines can be used:

• Initial dose: 5,000 units by intravenous injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously
• Frequency: every 8 hours or every 12 hours
• Recommended dose: 8,000 to 10,000 units of a concentrated solution every 8 hours or 15,000 to 20,000 units of a concentrated solution every 12 hours It is essential to monitor the patient's coagulation test results and adjust the dosage accordingly to ensure the patient's safety and the effectiveness of the treatment 2.

From the Research

Heparin Dosing

• The weight-based heparin dosing nomogram is widely generalizable and has proved to be effective, safe, and superior to one based on standard practice 3.
• A study compared two weight-based heparin dosing nomograms and found that an 80-unit/kg bolus and 18-unit · kg(-1) · h(-1) initial infusion rate achieved therapeutic anticoagulation more rapidly than a 60-unit/kg bolus and 12-unit · kg(-1) · h(-1) initial infusion rate 4.
• Another study assessed a weight-based heparin nomogram and found that 42% of patients had initial supratherapeutic responses, and that age, prior warfarin therapy, and high initial infusion rate were predictive of a supratherapeutic response 5.

Therapeutic Range

• The therapeutic range for activated partial thromboplastin time (APTT) is generally considered to be 1.5 to 2.3 times the control value 3.
• A study found that patients with APTT values <60 seconds had an increased relative risk of recurrent cardiovascular events, and that higher APTT values were associated with bleeding 6.
• Another study found that the time to therapeutic APTT was significantly faster in patients treated with a weight-based heparin nomogram compared to historical controls 5.

Switching from Infusion to Subcutaneous Dosing

• There is no direct evidence in the provided studies on how to switch from infusion to subcutaneous dosing.
• However, a study on enoxaparin, a low-molecular-weight heparin, found that the timing of dosing was related to bleeding complications, and that delaying the first dose until 10 hours or more postoperatively was associated with fewer complications 7.