Dataset Information

Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?

ABSTRACT:

Background

Protocolled treatment with unfractionated heparin (UFH) is a subject of ongoing debate. Even though international guidelines prescribe calibration of the activated partial thromboplastin time (aPTT) to 0.3 to 0.7 U/mL anti-Xa activity to establish an UFH therapeutic range, evidence for this approach remains scarce. In this study, we evaluated different strategies to delineate the UFH therapeutic range and analyzed the effects on patient therapeutic classification.

Methods

In 109 patient samples, the aPTT was measured with 2 different reagents, both of which used mechanical clot detection. The UFH therapeutic range was determined using 3 previously described methods: calibration of the aPTT to 0.3 to 0.7 U/mL anti-Xa activity, application of 1.5 to 2.5 times the control aPTT, or using 0.3 to 0.7 U/mL anti-Xa activity directly. We also applied the UFH therapeutic range of a second hospital to our patient population.

Results

Application of the guideline-prescribed anti-Xa calibration method would result in patients receiving increased UFH dosage in comparison to our previous UFH nomogram. Between-method and between-laboratory variations in aPTT and anti-Xa activity assays are a likely cause of these discrepancies. Additionally, we show that individual patient characteristics, such as weight and UFH treatment duration, likely contribute to the discordance between different strategies to establish an UFH therapeutic range.

Conclusion

No consensus is reached between different strategies to define the UFH therapeutic range, which could result in relevant differences in UFH doses applied in patients. Clinicians and laboratory specialists should critically evaluate UFH monitoring protocols and be aware of their shortcomings.

SUBMITTER: Coene KLM

PROVIDER: S-EPMC6714639 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?

Coene Karlien L M KLM van der Graaf Fedde F van de Kerkhof Daan D

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20161116 1

<h4>Background</h4>Protocolled treatment with unfractionated heparin (UFH) is a subject of ongoing debate. Even though international guidelines prescribe calibration of the activated partial thromboplastin time (aPTT) to 0.3 to 0.7 U/mL anti-Xa activity to establish an UFH therapeutic range, evidence for this approach remains scarce. In this study, we evaluated different strategies to delineate the UFH therapeutic range and analyzed the effects on patient therapeutic classification.<h4>Methods</ ...[more]

PMID: 27856667

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Project description:BackgroundUnfractionated heparin (UFH) is an anticoagulant drug that is considered a high-risk medication because an excessive dose can cause bleeding, whereas an insufficient dose can lead to a recurrent embolic event. Therapeutic response to the initiation of intravenous UFH is monitored using activated partial thromboplastin time (aPTT) as a measure of blood clotting time. Clinicians iteratively adjust the dose of UFH toward a target, indication-defined therapeutic aPTT range using nomograms, but this process can be imprecise and can take ≥36 hours to achieve the target range. Thus, a more efficient approach is required.ObjectiveIn this study, we aimed to develop and validate a machine learning (ML) algorithm to predict aPTT within 12 hours after a specified bolus and maintenance dose of UFH.MethodsThis was a retrospective cohort study of 3019 patient episodes of care from January 2017 to August 2020 using data collected from electronic health records of 5 hospitals in Queensland, Australia. Data from 4 hospitals were used to build and test ensemble models using cross-validation, whereas data from the fifth hospital were used for external validation. We built 2 ML models: a regression model to predict the aPTT value after a UFH bolus dose and a multiclass model to predict the aPTT, classified as subtherapeutic (aPTT <70 seconds), therapeutic (aPTT 70-100 seconds), or supratherapeutic (aPTT >100 seconds). Modeling was performed using Driverless AI (H2O), an automated ML tool, and 17 different experiments were iteratively conducted to optimize model accuracy.ResultsIn predicting aPTT, the best performing model was an ensemble with 4x LightGBM models with a root mean square error of 31.35 (SD 1.37). In predicting the aPTT class using a repurposed data set, the best performing ensemble model achieved an accuracy of 0.599 (SD 0.0289) and an area under the receiver operating characteristic curve of 0.735. External validation yielded similar results: root mean square error of 30.52 (SD 1.29) for the aPTT prediction model, and accuracy of 0.568 (SD 0.0315) and area under the receiver operating characteristic curve of 0.724 for the aPTT multiclassification model.ConclusionsTo the best of our knowledge, this is the first ML model applied to intravenous UFH dosing that has been developed and externally validated in a multisite adult general medical and surgical inpatient setting. We present the processes of data collection, preparation, and feature engineering for replication.

Project description:BackgroundPatients hospitalized with severe acute respiratory syndrome coronavirus 2 infection are at risk for thrombotic complications necessitating use of therapeutic unfractionated heparin (UFH). Full-dose anticoagulation limits requirements for organ support interventions in moderately ill patients with coronavirus disease 2019 (COVID-19). Given this benefit, it is important to evaluate response to therapeutic anticoagulation in this population.ObjectivesThe aim of this study was to assess therapeutic UFH infusions and associated bleeding risk in patients with COVID-19.Patients/methodsThis retrospective cohort study includes patients at Brigham and Women's Hospital, Boston, Massachusetts, receiving weight-based nursing-nomogram titrated UFH infusion during a 10-week surge in COVID-19 hospitalizations. Of 358 patients on therapeutic UFH during this interval, 97 (27.1%) had confirmed COVID-19. Patient characteristics, laboratory values, and information regarding UFH infusion and bleeding events were obtained from the electronic medical record.ResultsPatients who were COVID-19 positive had fewer therapeutic activatrd partial thromboplastin times (aPTTs) compared to COVID-19-negative patients (median rate, 40.0% vs 53.1%; P < .0005). Both major and clinically relevant nonmajor bleeding were increased in COVID-19-positive patients, with major bleeding observed in 10.3% (95% confidence interval [CI], 5.7%-17.9%) of patients who were COVID-19 positive and 3.1% (95% CI, 1.6%-5.9%) of patients who were COVID-19 negative (P < .005). In logistic regression, bleeding events were associated with receiving UFH for longer than 7 days, but not platelet count, coagulation, or inflammatory measurements.ConclusionsOur data indicate a higher incidence of bleeding complications in patients with COVID-19 receiving weight-based nursing-nomogram titrated UFH infusions despite a higher prevalence of subtherapeutic aPTTs in this population. These data underscore the need for prospective studies aimed at improving the quality and safety of therapeutic anticoagulation in patients with COVID-19.

Dataset Information

Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?

Background

Methods

Results

Conclusion

Publications

Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?

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