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Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease.

ABSTRACT: Background:Intravenous unfractionated heparin infusion is often used to minimize the duration of time without anticoagulation around delivery in pregnant patients with high thrombotic risk. Activated partial thromboplastin time is commonly used to monitor and adjust heparin dose. However, using activated partial thromboplastin time is problematic in pregnancy because activated partial thromboplastin time response to unfractionated heparin is attenuated due to elevated Factor VIII levels and may lead to incorrect dosing. Case:We report a case of deep venous thrombosis occurring in a term pregnancy managed by intravenous unfractionated heparin adjusted using anti-Xa level around the time of delivery. We modified the intravenous unfractionated heparin nomogram by using anti-Xa levels instead of activated partial thromboplastin time and observed lower dosing of unfractionated heparin than otherwise required to achieve and maintain target levels. Conclusion:This report demonstrates the feasibility and effectiveness of using anti-Xa level to monitor and adjust intravenous unfractionated heparin infusion in pregnancy.

SUBMITTER: Tse E

PROVIDER: S-EPMC6734630 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease.

Tse Enrica E Khurana Rshmi R Clarke Gwen G Sia Winnie W

Obstetric medicine 20180517 3

<h4>Background</h4>Intravenous unfractionated heparin infusion is often used to minimize the duration of time without anticoagulation around delivery in pregnant patients with high thrombotic risk. Activated partial thromboplastin time is commonly used to monitor and adjust heparin dose. However, using activated partial thromboplastin time is problematic in pregnancy because activated partial thromboplastin time response to unfractionated heparin is attenuated due to elevated Factor VIII levels ...[more]

PMID: 31523272

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Project description:To evaluate the hypothesis that patients with a history of intravenous drug misuse (IVDM) initiated on weight-based heparin infusions require higher than expected infusion rates to achieve therapeutic activated partial thromboplastin time (aPTT). This study is a multicenter, retrospective chart review of patients with a history of IVDM who were admitted to an acute care site between 10/1/2015 and 9/30/2020 and treated with continuous heparin infusions. Patients were identified using ICD9 and ICD10 codes and included if they had a documented history of IVDM within the past six months. Variables of particular interest included: median heparin infusion rates to maintain therapeutic aPTT, average time to reach therapeutic aPTT, and International Society of Thrombosis and Haemostasis Criteria for moderate to severe bleeding. Of the 41 patients who met the inclusion and exclusion criteria, 39 achieved therapeutic aPTT while on a weight-based heparin infusion. All heparin infusions were initiated at a rate of 18 units/kg/hr then titrated per institutional heparin infusion protocols. The mean time to therapeutic aPTT was 38.48 h ± 26.4 h with a mean infusion rate of 27.64 ± 7.14 units/kg/hr. To maintain therapeutic anticoagulation, infusion rates 150% higher than the initial rate were required. Of the 39 patients who achieved therapeutic aPTT, 85% (33) met criteria for heparin resistance, defined as greater than 35,000 units of heparin daily. No statistical significance could be derived from this retrospective chart review as therapeutic heparin rates were evaluated in comparison to initial infusion rate, rather than a control group. The findings in this study demonstrate a possible clinical association of the reduced antithrombin activity previously described in opiate misusers. To efficiently achieve therapeutic anticoagulation, it may be appropriate to consider use of heparin antiXa monitoring in place of aPTT or utilization of increased initial heparin infusion rates.

Project description:Continuous intravenous unfractionated heparin (UFH) is administered routinely in the intensive care unit (ICU) for the anticoagulation of patients, and monitoring is performed by the activated partial thromboplastin time (APTT) or anti-Xa activity. However, these strategies are associated with potentially large time intervals before dose adjustments, which could be detrimental to the patient. The aim of the study was to compare a point-of-care (POCT) version of the APTT to (i) laboratory-based APTT and (ii) measurements of anti-Xa activity in terms of correlation, agreement and turnaround time (TAT). Thirty-five ICU patients requiring UFH therapy were prospectively included and followed longitudinally for a maximum duration of 15 days. UFH was administered according to a local adaptation of Raschke and Amanzadeh’s aPTT nomograms. Simultaneous measurements of POCT-APTT (CoaguCheck® aPTT Test, Roche Diagnostics) on a drop of fresh whole blood, laboratory-based APTT (C.K. Prest®, Stago) and anti-Xa activity (STA®Liquid anti-Xa, Stago) were systematically performed two to six times a day. Antithrombin, C-reactive protein, fibrinogen, factor VIII and lupus anticoagulant were measured. The time tracking of sampling and analysis was recorded. The overall correlation between POCT-APTT and laboratory APTT (n = 795 pairs) was strongly positive (rs = 0.77, p < 0.0001), and between POCT-APTT and anti-Xa activity (n = 729 pairs) was weakly positive (rs = 0.46, p < 0.0001). Inter-method agreement (Cohen’s kappa (k)) between POCT and laboratory APTT was 0.27, and between POCT and anti-Xa activity was 0.30. The median TATs from sample collection to the lab delivery of results for lab-APTT and anti-Xa were 50.9 min (interquartile range (IQR), 38.4−69.1) and 66.3 min (IQR, 49.0−91.8), respectively, while the POCT delivered results in less than 5 min (p < 0.0001). Although the use of the POCT-APTT device significantly reduced the time to results, the results obtained were poorly consistent with those obtained by lab-APTT or anti-Xa activity, and therefore it should not be used with the nomograms developed for lab-APTT.

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.

Dataset Information

Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease.

Publications

Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease.

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