Inpatient Monitoring of Unfractionated Heparin

Vanderbilt University Medical Center

Status: Invitation-only

Conditions: Blood Clot; Thrombosis

Treatments: Other: anti-Xa protocol; Other: PTT protocol

Study type: Interventional

Funder types: Other

Identifiers

NCT06329921

232192

Details and patient eligibility

About

Unfractionated heparin (UFH) is the most widely used intravenous (IV) anticoagulant for treating and preventing thromboembolic disease (e.g., blood clots ). UFH must be closely monitored and adjusted in the hospital. There are two assays used to monitor UFH: 1) the activated partial thromboplastin time (PTT) and 2) the chromogenic anti-factor Xa assay (anti-Xa). This study aims to compare PTT and anti-Xa methods for monitoring UFH in a pragmatic, randomized controlled trial to determine which helps patients reach a therapeutic anticoagulation range faster.

Full description

Unfractionated heparin (UFH) is the most widely used intravenous (IV) anticoagulant for the treatment and prevention of thromboembolic disease (e.g., blood clots ). When administered by intravenous injection, the onset of action is immediate. Indications for use of UFH include venous thromboembolism, acute coronary syndrome, and acute ischemic stroke. UFH is used to prevent thrombosis in the setting of arrhythmias, extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and endovascular procedures. The unpredictable pharmacokinetics of UFH and interpatient variability result in a narrow therapeutic index restricting its use to the hospital setting with close monitoring and adjustments.

Two validated assays exist and are in use at the VUMC adult hospital for the monitoring of unfractionated heparin: 1) the activated partial thromboplastin time (PTT) and 2) the chromogenic anti-factor Xa assay (anti-Xa). At VUMC, the PTT protocol is managed by nursing; the anti-Xa protocol is managed by clinical pharmacy. Both are clinically acceptable methods for titration and adjustment of unfractionated heparin. Assessing the therapeutic effect of unfractionated heparin is most often performed with the PTT, which requires institutional calibration to a specific heparin level to account for the variable PTT responses with different commercial reagents and laboratory instruments. The PTT can be influenced by various elements during sample processing, laboratory analysis, and patient biological factors that may cause it to be an inaccurate indication of the degree of anticoagulation. This can lead to patients not getting the correct heparin dosing for their clinical needs.

The anti-Xa assay is another method of measuring the degree of therapeutic effect of heparin. In routine clinical practice the anti-Xa is not as widely available and less familiar among many providers. This assay can be impacted by variability in sample collection and processing and laboratory analysis. Compared to the PTT assay, however, it is much less influenced by patient-specific biological factors. This may help improve heparin monitoring and titration to ensure patients receive therapeutic levels of anticoagulation and do not get too much or too little heparin. However, large studies using anti-Xa for management of heparin in the treatment of venous thromboembolism have not been performed.

PTT and anti-Xa heparin monitoring protocols have not been compared in a prospective, randomized setting. The study team will conduct a pragmatic, randomized clinical trial comparing the effectiveness of both methods for optimal monitoring of intravenous unfractionated heparin for systemic anticoagulation in hospitalized adult patients.

Enrollment: 2,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients at Vanderbilt University Hospital age 18 years and older who are admitted as observation or inpatients for whom intravenous unfractionated heparin (monitored via the PTT nurse-managed protocol) is ordered.
• Baseline PTT value is ≥0 and ≤ 36.0 seconds
• Baseline heparin level anti-Xa assay value is ≥0 and ≤0.3

Exclusion criteria

• Indication for anticoagulation is extracorporeal membrane oxygenation or cerebrovascular ischemic event.
• Provider determines patient is not appropriate for the study.

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,000 participants in 2 patient groups

Active Comparator: PTT protocol

Active Comparator group

Description:

Patients randomized to this arm will be monitored using the nurse-managed PTT guided protocol. This includes patients on both high- and low-dose heparin protocols.

Treatment:

Other: PTT protocol

Active Comparator: anti-Xa protocol

Active Comparator group

Description:

Patients randomized to this arm will be monitored using the pharmacy-managed anti-Xa protocol. This includes patients on both high- and low-dose heparin protocols.

Treatment:

Other: anti-Xa protocol