Antithrombin / Protein C deficiency in pregnancy

Key points

  • Thrombosis and thromboembolism continue to be the leading direct cause of maternal death in the UK.
  • Among the most important risk factors for venous thromboembolism in pregnancy is the presence of thrombophilia such as antithrombin deficiency.
  • Work to reduce risk of VTE in this group of women could contribute to reducing maternal mortality.

Surveillance period

1st July 2019 – 30th June 2020

Background

Thrombosis and thromboembolism remain one of the biggest causes of maternal death during pregnancy in the UK[1] and therefore preventing thrombosis continues to be an important intervention in pregnancy. Inherited thrombophilias, including antithrombin and protein C deficiency, are important risk factors for venous thromboembolism (VTE). Pregnant women are already at increased risk of VTE due to their hypercoagulable state so those with antithrombin deficiency are therefore at very high risk of VTE.[2] There is a lack of straightforward guidance or a strong evidence base for management of antithrombin deficiency in pregnancy and it is currently unknown how this cohort of women is managed in the UK. It is believed that protein C deficiency may increase the risk of pregnancy loss but the incidence of miscarriage and stillbirth in women with severe protein C deficiency is unknown. This study will help us estimate the current prevalence of antithrombin III and heterozygous protein C deficiency among pregnant women in the UK and describe treatment methods and outcomes with a view to developing guidance to identify women at risk, improve management and reduce VTE risk in this group.

Objective

To use the UK Obstetric Surveillance System (UKOSS) to determine the prevalence of antithrombin/protein c deficiency in pregnant women in the UK and examine the management of the condition as well maternal and neonatal outcomes.

Research questions

  • What is the prevalence of antithrombin/protein C deficiency in pregnancy in the UK?
  • How are pregnant women with antithrombin/protein C deficiency managed in the UK?
  • What factors influence clinician’s choice of treatment and when to treat?
  • What is the incidence of maternal morbidity and mortality in this cohort?
  • What is the incidence of neonatal morbidity and mortality in this cohort?

Case definition

Antithrombin Deficiency:

Any pregnant woman with known antithrombin deficiency and found to have an antithrombin level below the lower limit of normal for their local reference laboratory.

Protein C Deficiency:

Any pregnant woman with known protein C deficiency and found to have a protein C level below the lower limit of normal for their local reference laboratory.

Funding

This study is being funded by Oxford Centre for Haematology and Biomedical Research Centre Haematology Theme.

Ethics committee approval

This study has been approved by the North London REC1 (Ref. Number: 10/H0717/20).

Lead investigators

Rachel Farnell, Sue Pavord and Ingrid Granne, Oxford University Hospitals NHS Trust

References

  1. ^ Knight M, Nair M, Tuffnell D, Shakespeare J, Brocklehurst P, et al. Saving Lives, Improving Mothers’ Care – Surveillance of maternal deaths in the UK 2011-13 and lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009-13. National Perinatal Epidemiology Unit, University of Oxford; 2015
  2. ^ Bauer KA, Issues in the Diagnosis and Management of Hereditary Antithrombin Deficiency. Ann Pharmacother. 2016, Sep;50(9):758-67