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Time in therapeutic range as a marker for thrombotic and bleeding outcomes in Fontan patients

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Abstract

Fontan patients managed with warfarin are at risk not only for thrombotic events, but also for bleeding episodes as a consequence of anticoagulation treatment. The aim of this study was to determine whether time spent in patient specified therapeutic range (TTR), when managed in a cardiology-based pharmacist managed anticoagulation clinic (PMAC), is a useful target metric for monitoring, as well as improving outcomes. A single center retrospective review was conducted evaluating TTR of all Fontan patients (n = 45) on warfarin managed in our outpatient cardiology pharmacist managed anticoagulation clinic (PMAC) during a 19 month time frame. The primary outcome was time spent within, above, and below therapeutic range. Secondary outcomes were thrombotic event (TE) incidence pre- and post PMAC enrollment and bleeding event incidence during PMAC management. Of the Fontan patients included, 55.6% were male and the median age at latest anticoagulation clinic follow-up was 19 years (IQR 13, 29). A composite 52.9 patient years of warfarin therapy was evaluated during the study time frame. The mean TTR for patients was 84.1 ± 5.2%. The most frequent reasons for non-therapeutic INRs were diet changes (42.8%), medication non-compliance (13.7%), and drug interactions (8.8%). Only one TE occurred during the study time frame. The incidence of TE in this population was decreased after PMAC enrollment (1 per 52.9 patient year versus 1 event per 17.4 patient year; p < 0.0002). Two major bleeds that required emergency department visit occurred during this time, none were cerebral or gastrointestinal. In Fontan patients anticoagulated with warfarin, a greater than 80% TTR can be achieved in a PMAC. Such high time in therapeutic range was associated with excellent outcomes, despite the obvious complexity of this population.

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Abbreviations

PMAC:

Pharmacist managed anticoagulation clinic

TTR:

Time in therapeutic range

INR:

International normalized ratio

TEE:

Transesophageal echocardiogram

SD:

Standard deviation

TE:

Thrombotic event

BMI:

Body mass index

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Author contributions

All authors take responsibility for the content of the manuscript. All authors have approved the manuscript and agree with submission to the Journal of Thrombosis and Thrombolysis. Dr. JF and KM wrote the first draft of the manuscript. TA, NN, RN; JC, RN; TM, PhD; JSP, MD; AAV, PharmD PhD FCP and GRV, MB ChB FRCP reviewed the included studies in the meta-analysis. Dr. CCA critically revised the manuscript. Dr. JSP wrote the hematology part of the manuscript and Dr. GV is the senior author on the manuscript. Dr. GV is the corresponding author.

Funding

The authors received no funding related to this work. There are no relevant financial conflicts. There was no honorarium, grant or other form of payment given to produce the manuscript and no relation to industry.

Author information

Authors and Affiliations

  1. Division of Pharmacy, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jenna M. Faircloth

  2. Research Fellowship Program, Pharmacy Research, Division of Research in Patient Services, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Kristin M. Miner

  3. Department of Pediatric Cardiology, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Tarek Alsaied, Nicole Nelson & Julie Ciambarella

  4. Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Tomoyuki Mizuno

  5. Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USA

    Joseph S. Palumbo

  6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Alexander A. Vinks

  7. Adolescent and Adult Congenital Program, Children’s Heart Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, USA

    Gruschen R. Veldtman

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  1. Jenna M. Faircloth
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  2. Kristin M. Miner
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  3. Tarek Alsaied
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  4. Nicole Nelson
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  7. Joseph S. Palumbo
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  9. Gruschen R. Veldtman
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Corresponding author

Correspondence to Gruschen R. Veldtman.

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Faircloth, J.M., Miner, K.M., Alsaied, T. et al. Time in therapeutic range as a marker for thrombotic and bleeding outcomes in Fontan patients. J Thromb Thrombolysis 44, 38–47 (2017). https://doi.org/10.1007/s11239-017-1499-8

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  • DOI: https://doi.org/10.1007/s11239-017-1499-8

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