Activated Clotting Time (ACT) for Monitoring of Low-Dose Heparin: Performance Characteristics in Healthy Adults and Critically Ill Patients

Abstract

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.

Comments on ‘Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure’: the bitter truth about unfractionated heparin monitoring assays

“…Concerning the monitoring of heparin, we agree that APTT and ACT poorly correlate with each other and with anti-Xa levels in critically ill patients. Our own group recently confirmed this observation using two modern ACT devices with different detection methods [6]. As outlined in the current paper, we employed additional anti-Xa measurements whenever APTT or ACT was inconsistent with heparin dose or clinical picture.…”

A Comparison of Activated Partial Thromboplastin Time and Activated Coagulation Time for Anticoagulation Monitoring during Extracorporeal Membrane Oxygenation Therapy

“…17 This might be because ACT is a whole blood-based measurement technique that has no exclusive sensitivity to unfractionated heparin and is not capable of differentiating between the affecting variables. 21 ACT was unable to differentiate between low and therapeutic levels of anticoagulation when using the aPTT as the reference. 20 Bleeding may occur in any part of the body, such as the intubation or catheter insertion site, the respiratory tract, the digestive tract, the urinary tract, the brain, the skin and mucous membranes, or a surgical incision.…”

“…17 This might be because ACT is a whole blood–based measurement technique that has no exclusive sensitivity to unfractionated heparin and is not capable of differentiating between the affecting variables. 21 ACT was unable to differentiate between low and therapeutic levels of anticoagulation when using the aPTT as the reference. 20…”

Coagulation Function Testing Clinical Demand and Current Status in China

“…Regarding heparin medication, although APTT is also used as a monitoring index, ACT has greater advantages in high-dose heparin medication situations (Wehner JE, et al, 2020, Liu Y, Yuan Z, Han X, Song K & Xing J, 2023Simko RJ, Tsung FF & Stanek EJ, 1995). Therefore, in situations such as CPB and ECMO that require high-dose heparin application, ACT is often used as the core coagulation function monitoring index to assist anticoagulation treatment.…”