Automated Heparin-Delivery System to Control Activated Partial Thromboplastin Time

Abstract

Background-Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. Methods and Results-We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within Ϯ10 seconds of the target (prespecified primary end point), and 89% were within a Ϯ15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range Ϯ15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. Conclusions-These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice. (Circulation. 1999;99:751-756.)

Automation and interoperability of a nurse-managed insulin infusion protocol as a model to improve safety and efficiency in the delivery of high-alert medications

“…The risk of other medication infusions such as heparin is also commonly mitigated by an independent nurse double check calculation. 36 There is also a growing body of evidence to support the belief that automation achieves better control to targets. Automated closed-loop infusion models have been shown to effectively reach and maintain target outcomes for mean arterial pressure during vasopressor infusion in a simulated model.…”

Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

“…Several complex PKPD models have been reported incorporating linear and non-linear elimination and pharmacodynamic structures. 5 – 7 However, such models require enough data to identify multiple internal parameters and can introduce redundancy with multiple optimal parameter values. Given the limited number of data values per patient, the choice was made to fit only a one- or two-compartment model with parameters that could be fitted reliably to the data.…”

Pharmacokinetic/pharmacodynamic modeling for dose selection for the first‐in‐human trial of the activated Factor XII inhibitor garadacimab (CSL312)

“…17,18 For aPTT prediction, the power and intercept factors are based on parameters estimated in monkeys as well as previous publications. 19,20 First-in-human dose selection and exposure margins…”