Monitoring Heparin with the Anti-Xa assay

From Crystal Azavedo: Hi George, Are you aware of any observation or randomized controlled trial data that compares bleeding and thrombosis risk in patients receiving unfractionated heparin monitored with the activated partial thromboplastin time (aPTT, PTT) compared to monitoring with anti-Xa? In other words, are there clinical outcome data that suggest monitoring with anti-Xa improves patient outcomes? Thanks!! Crystal

Hi, Crystal. First, let me tell you about a lab that recently ran parallel PTTs and chromogenic anti-Xa heparin assays on their unfractionated heparin patients over several days’ time, hundreds of assays. The specialty techs have carefully validated their PTT target therapeutic range to anti-Xa using the Brill-Edwards curve method for over ten years, and have always considered their PTTs to be rock-solid. In comparing results they found a 40% disagreement, meaning that in 40% of the cases, anti-Xa results that were in range paired up with PTT results that were either above or below, conversely, anti-Xa results that were high or low paired with PTT results that were within range. There were many instances in which patient dosages would have been inappropriately modified based on the PTT results. It may be that the PTT is simply too prone to interference to be reliable for monitoring unfractionated heparin. Audio Module 20, Monitoring Antithrombotic Therapy 1, addresses PTT interferences.

Fortunately, Dr. Paul Riley, Diagnostica Stago Inc, maintains a bibliography of heparin monitoring studies, and  provides this list of articles that compare PTT and anti-Xa results to outcomes:

• Rosborough et al. Monitoring unfractionated heparin therapy with antifactor Xa activity results in fewer monitoring tests and dosage changes than monitoring with the activated partial thromboplastin time. Pharmacotherapy 1999;19: 760-766.
• Vandiver, Vondracek. Achieving target antifactor Xa activity with a heparin protocol based on sex, age, height, and weight. Pharmacotherapy 2004;24:713-719.
• Weitz et al.. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy 2012;32: 546-558.
• Barrowcliffe et al. Inability of the activated partial thromboplastin time to predict heparin levels. Arch Inter Med 1997;157: 2475-9.
• Garcia et al. Monitoring unfractionated heparin with the aPTT: Time for a fresh look. Thrombosis Haemost 2006;96: 547-52.
• Rosborough. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994;154: 46-56.
• Rosborough et al. Comparison of anti-factor Xa heparin activity and activated partial thromboplastin time in 2,773 plasma samples from unfractionated heparin-treated patients. Amer J Clin Pathol 1997;108: 662-8.

I want to thank Dr. Riley for the opportunity to use his list, and a hope this helps you. Geo.