Validating two divergent activated clotting time tests of heparin anticoagulation in cardiac surgical patients and in vitro.
Thesis event information
Date and time of the thesis defence
Topic of the dissertation
Validating two divergent activated clotting time tests of heparin anticoagulation in cardiac surgical patients and in vitro.
Doctoral candidate
A Doctor of Medicine, MD Janne Moilanen
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Research Unit of Translational Medicine
Subject of study
Anesthesiology and intensive care
Opponent
Docent Jenni Toivonen, University hospital of Turku
Custos
Docent Tiina Erkinaro, University hospital of Oulu
Validating two divergent activated clotting time tests of heparin anticoagulation in cardiac surgical patients and in vitro.
Unfractionated heparin is used perioperatively for anticoagulation, and its effect is commonly monitored by measuring activated clotting time (ACT). However, ACT tests lack standardization, can be influenced by many factors besides heparin, and variably correlate with anti-factor Xa activity, which is considered the gold standard. This thesis evaluated the validity of two divergently activated ACT tests, the Hemochron ACT-LR and ACT+, in monitoring heparin anticoagulation in severe factor XII deficiency, in detecting post-protamine residual heparin in cardiac surgical patients, and under low to moderate heparin concentrations in vitro.
Study I reports, for the first time in the scientific literature, on the successful use of a standard ACT test to monitor heparin anticoagulation in cardiac surgical patients with severe factor XII deficiency. The ACT+ test was successfully used to guide heparin dosing in two patient cases. In vitro, the baseline values of the ACT+ test were low and demonstrated a seemingly linear dose-response relationship with increasing heparin concentration.
Study II evaluated in 51 cardiac surgical patients the ability of ACT-LR, ACT+, and ROTEM sigma to detect residual heparin ten to fifteen minutes after protamine administration. Overall, the performance of all three methods was poor. Yet, the ACT+ test demonstrated some diagnostic capability, whereas the ACT-LR and ROTEM sigma had no diagnostic value.
In Study III, donor blood samples were spiked with heparin to concentrations of 0-2.5 IU/ml, corresponding to the designated reference range of the ACT-LR test. Although the ACT+ test is optimized for higher heparin concentrations, the performance of ACT+ was equal to that of ACT-LR up to concentration of 0.5 IU/ml, above which the ACT+ test was superior to the ACT-LR test.
These findings question the value of the ACT-LR test in monitoring heparin anticoagulation since the ACT+ test demonstrates superior, or at least equivalent, diagnostic performance in clinical and observational settings, even at low to moderate heparin concentrations. Furthermore, the ACT+ test has the exclusive ability to monitor heparin anticoagulation in patients with severe factor XII deficiency.
Study I reports, for the first time in the scientific literature, on the successful use of a standard ACT test to monitor heparin anticoagulation in cardiac surgical patients with severe factor XII deficiency. The ACT+ test was successfully used to guide heparin dosing in two patient cases. In vitro, the baseline values of the ACT+ test were low and demonstrated a seemingly linear dose-response relationship with increasing heparin concentration.
Study II evaluated in 51 cardiac surgical patients the ability of ACT-LR, ACT+, and ROTEM sigma to detect residual heparin ten to fifteen minutes after protamine administration. Overall, the performance of all three methods was poor. Yet, the ACT+ test demonstrated some diagnostic capability, whereas the ACT-LR and ROTEM sigma had no diagnostic value.
In Study III, donor blood samples were spiked with heparin to concentrations of 0-2.5 IU/ml, corresponding to the designated reference range of the ACT-LR test. Although the ACT+ test is optimized for higher heparin concentrations, the performance of ACT+ was equal to that of ACT-LR up to concentration of 0.5 IU/ml, above which the ACT+ test was superior to the ACT-LR test.
These findings question the value of the ACT-LR test in monitoring heparin anticoagulation since the ACT+ test demonstrates superior, or at least equivalent, diagnostic performance in clinical and observational settings, even at low to moderate heparin concentrations. Furthermore, the ACT+ test has the exclusive ability to monitor heparin anticoagulation in patients with severe factor XII deficiency.
Last updated: 26.5.2025