Anti-factor Xa and activated partial thromboplastin time measurements for heparin monitoring in mechanical circulatory support

JACC Heart Fail. 2015 Apr;3(4):314-22. doi: 10.1016/j.jchf.2014.11.009. Epub 2015 Mar 11.

Abstract

Objectives: This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs).

Background: CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events.

Methods: A prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels.

Results: A total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001).

Conclusions: Levels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

Keywords: activated partial thromboplastin time; anti-factor Xa; continuous-flow left ventricular assist device; intravenous unfractionated heparin; monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage*
  • Drug Administration Schedule
  • Factor Xa Inhibitors / metabolism*
  • Female
  • Gastrointestinal Hemorrhage / prevention & control
  • Heart Failure / therapy*
  • Heart-Assist Devices / adverse effects*
  • Hemolysis / physiology
  • Heparin / administration & dosage*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Partial Thromboplastin Time / methods
  • Prospective Studies
  • Prosthesis Failure / adverse effects
  • Thromboembolism / prevention & control
  • Treatment Outcome
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Warfarin
  • Heparin