Observational Study

. 2021 Sep;107(17):1390-1397.

doi: 10.1136/heartjnl-2020-317397. Epub 2020 Nov 24.

Bleeding and thrombotic risk in pregnant women with Fontan physiology

Andrea Girnius¹, Dominica Zentner^{2

3}, Anne Marie Valente⁴, Petronella G Pieper⁵, Katherine E Economy⁶, Magalie Ladouceur^{7

8}, Jolien W Roos-Hesselink⁹, Carri Warshak¹⁰, Sara L Partington^{11

12}, Zhiqian Gao¹³, Nicholas Ollberding^{14

15}, Michelle Faust¹³, Saulius Girnius¹⁶, Harald Kaemmerer¹⁷, Nicole Nagdyman¹⁷, Scott Cohen¹⁸, Mary Canobbio¹⁹, Teiji Akagi²⁰, Jasmine Grewal²¹, Elisa Bradley²², Yonathan Buber²³, Joseph Palumbo²⁴, Niki Walker²⁵, Jamil Aboulhosn²⁶, Erwin Oechslin^{27

28}, Helmut Baumgartner²⁹, Wesam Kurdi³⁰, Wendy M Book³¹, Barbara J M Mulder³², Gruschen R Veldtman³³

Affiliations

¹ Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
² Department of Cardiology and Department of Genomic Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
³ Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Brigham and Women's Hospital, Department of Medicine, Division of Cardiovascular Disease, Department of Cardiology Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Brigham and Women's Hospital, Department of Obstetrics and Gynecology, Division Maternal Fetal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁷ Cardiology, Hopital Europeen Georges Pompidou, Paris, France.
⁸ Pediatric Cardiology, Hopital Universitaire Necker-Enfants Malades, Paris, France.
⁹ Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
¹⁰ Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹¹ Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹² Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹³ Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁴ Department of Pediatrics, Cincinnati Children's Hospital Medical Centre, Cincinnati, Ohio, USA.
¹⁵ Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁶ Department of Hematology, Trihealth Cancer Institute, Cincinnati, Ohio, USA.
¹⁷ Deutsches Herzzentrum München, Germany, Munich, Germany.
¹⁸ Department of Cardiology, The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁹ School of Nursing, University of California Los Angeles, Los Angeles, California, USA.
²⁰ Cardiovascular Medicine, Okayama University, Okayama, Japan.
²¹ Cardiology, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
²² Adult Congenital Heart Disease, The Ohio State University & Nationwide Children's Hospital, Nationwide Children's Hospital, Columbus, Ohio, USA.
²³ Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
²⁴ Haematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
²⁵ Golden Jubilee Hospital, Glasgow, UK.
²⁶ Ahmanson/UCLA ACHD Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²⁷ Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Heatlh Network and University of Toronto, Toronto, Ontario, Canada.
²⁸ Bitove Family Professorship of Adult Congenital Heart Disease, Toronto General Hospital, Toronto, Ontario, Canada.
²⁹ Department of Cardiology III: Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Albert Schweitzer Campus 1, Building A1, 48149 Muenster, Germany.
³⁰ King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
³¹ Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA.
³² Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
³³ Adult Congenital Heart Disease, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia gruschen@me.com.

PMID: 33234672
PMCID: PMC10367127
DOI: 10.1136/heartjnl-2020-317397

Observational Study

Bleeding and thrombotic risk in pregnant women with Fontan physiology

Andrea Girnius et al. Heart. 2021 Sep.

. 2021 Sep;107(17):1390-1397.

doi: 10.1136/heartjnl-2020-317397. Epub 2020 Nov 24.

Authors

Affiliations

¹ Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
² Department of Cardiology and Department of Genomic Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
³ Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Brigham and Women's Hospital, Department of Medicine, Division of Cardiovascular Disease, Department of Cardiology Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Brigham and Women's Hospital, Department of Obstetrics and Gynecology, Division Maternal Fetal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁷ Cardiology, Hopital Europeen Georges Pompidou, Paris, France.
⁸ Pediatric Cardiology, Hopital Universitaire Necker-Enfants Malades, Paris, France.
⁹ Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
¹⁰ Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹¹ Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹² Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹³ Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁴ Department of Pediatrics, Cincinnati Children's Hospital Medical Centre, Cincinnati, Ohio, USA.
¹⁵ Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁶ Department of Hematology, Trihealth Cancer Institute, Cincinnati, Ohio, USA.
¹⁷ Deutsches Herzzentrum München, Germany, Munich, Germany.
¹⁸ Department of Cardiology, The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁹ School of Nursing, University of California Los Angeles, Los Angeles, California, USA.
²⁰ Cardiovascular Medicine, Okayama University, Okayama, Japan.
²¹ Cardiology, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
²² Adult Congenital Heart Disease, The Ohio State University & Nationwide Children's Hospital, Nationwide Children's Hospital, Columbus, Ohio, USA.
²³ Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
²⁴ Haematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
²⁵ Golden Jubilee Hospital, Glasgow, UK.
²⁶ Ahmanson/UCLA ACHD Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²⁷ Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Heatlh Network and University of Toronto, Toronto, Ontario, Canada.
²⁸ Bitove Family Professorship of Adult Congenital Heart Disease, Toronto General Hospital, Toronto, Ontario, Canada.
²⁹ Department of Cardiology III: Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Albert Schweitzer Campus 1, Building A1, 48149 Muenster, Germany.
³⁰ King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
³¹ Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA.
³² Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
³³ Adult Congenital Heart Disease, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia gruschen@me.com.

PMID: 33234672
PMCID: PMC10367127
DOI: 10.1136/heartjnl-2020-317397

Abstract

Background/objectives: Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.

Methods: We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.

Results: We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).

Conclusions: Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.

Keywords: Fontan physiology; pregnancy.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Anticoagulation strategy and bleeding events during pregnancy. Combo, combination of anticoagulation/antiplatelet medications; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VKA, vitamin K antagonist.

**Figure 2**
Selected factors associated with bleeding events by multivariate logistic regression. Combo, combination of anticoagulation/ antiplatelet medications; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VKA, vitamin K antagonist.

See this image and copyright information in PMC

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Bleeding and thrombotic risk in pregnant women with Fontan physiology

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Bleeding and thrombotic risk in pregnant women with Fontan physiology

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