Pregnancy, childbirth and neonatal outcomes in women with inherited bleeding disorders: a retrospective analysis.
Dr Lisa Clarke1,2, Dr Jennifer Curnow,3,4 Dr Briony Cutts5,6 , Dr Bryony Ross7,8 and Dr Giselle Kidson-Gerber9,10.
  1. Department of Haematology, Sydney Adventist Hospital, Sydney, Australia
  2. Transfusion Policy and Education, Australian Red Cross Lifeblood, Sydney, Australia
  3. Department of Haematology, Westmead Hospital, Sydney, Australia
  4. Faculty of Medicine and Health, University of Sydney, Sydney, Australia
  5. Department of Obstetrics, Royal Women’s Hospital, Melbourne , Australia
  6. Department of Obstetric Medicine, Joan Kirner Women’s and Children’s at Sunshine Hospital, Melbourne, Australia.
  7. Department of Haematology, Calvary Mater Newcastle, Australia
  8. NSW Health Pathology, North (Hunter), Newcastle, Australia
  9. Department of Haematology, Prince of Wales Hospital, Sydney, Australia
  10. Royal Hospital for Woman, Sydney, Australia
Corresponding author: Dr Lisa Clarke
Australia Red Cross Lifeblood
Sydney Processing Centre
17 O’Riordan street Alexandria 2015
LClarke@redcrossblood.org.au
+61411790679
Running title: Obstetric outcomes in inherited bleeding disorders
Abstract
Objective
To describe the characteristics and outcomes of women with inherited bleeding disorder during pregnancy and birth.
Design
Retrospective cohort study.
Setting
Tertiary care hospitals, NSW and Victoria Australia.
Population
100 women with inherited bleeding disorders, who birthed 134 live infants from 132 pregnancies.
Methods
Data was retrospectively obtained from the patient and neonatal medical records. Descriptive analysis was used to report maternal and pregnancy characteristics, birth and neonatal outcomes.
Main outcome measures
Factor replacement, neuraxial analgesia use and complications, post-partum haemorrhage and neonatal complications.
Results
PPH occurred in 22% of deliveries with primary PPH occurring in 20% and secondary PPH in 4% of births. 48% of PPHs were classified as major. PPHs occurred across the spectrum of IBD and was evenly distributed between women who had “normalised” their factor levels in pregnancy compared to those requiring factor at the time of birth. An obstetric cause was identified in more than half of PPHs.
Conclusions
Women with inherited bleeding disorders can deliver safely and receive neuraxial analgesia without complication when best practices are adhered to. PPH appears to occur at higher rates than the general population despite adequate factor levels or planned replacement. Whilst an obstetric cause was demonstrable in the many cases, these findings raise concern over the current definition of “adequate” factor levels at the time of birth.
Keywords
Inherited bleeding disorders, pregnancy, post-partum haemorrhage
Tweetable abstract:
Women with inherited bleeding disorders can deliver without complication when best practices are maintained.
Disclosures of interest.
Nil.
Contribution to authorship.
LJC collected data, analysed the data and wrote the manuscript.
JC critically appraised the manuscript.
BC collected data and critically appraised the manuscript.
BR collected data and critically appraised the manuscript
GKG conceived the idea, collected data and critically appraised the manuscript.
Ethics
Ethics approval was obtained through the human research ethics committee (SESLHD HREC 15/294).
Introduction
Pregnancy and childbirth pose unique haemostatic challenges. The associated risks and severity of potential bleeding complications are increased in women with inherited bleeding disorders (IBD) however appropriate measures can limit adverse outcomes. Guidelines are available to direct management of such women but there remains a paucity of published outcome data.
IBD affect approximately 1% of the population(1). In Australia 2643 women are registered with the Australian Bleeding Disorders Registry, with approximately 2/3 of reproductive age.(2)
Haemophilia A (HA) and B (HB) are X linked disorders, resulting in deficiencies of factors VIII (FVIII) and IX (FIX) respectively.(1) Most women are asymptomatic (carriers), however women with levels <40U/dL are classified as having mild disease.(3) In contrast to FIX levels, FVIII levels increase significantly throughout pregnancy and exceed recommended thresholds for birth in the majority of women.(3, 4) Maintaining factor levels >50U/dL are currently recommended for birth and 3-7 days post-partum depending on mode of birth(4). Neuraxial analgesia is deemed safe when levels are above this threshold.(4) Recombinant FVIII or FIX concentrates are the treatments of choice when factor levels are inadequate in HA and HB.(5)
von Willebrand disease (VWD) is the most common IBD and can be divided into 3 types(5). Types 1 and 3 represent quantitative defects of increasing magnitude whereas Type 2 represents a qualitative defect and can be further classified into Types 2A, B, M and N depending on the mechanism of disordered haemostasis. VWD has autosomal dominant inheritance in the less severe forms and autosomal recessive inheritance in the more severe types.(5) von Willebrand Factor (VWF) levels also rise in pregnancy. This increase is generally adequate in women with Type 1, fails to overcome the functional impairment in Type 2 and is insufficient in Type 3.(4) VWF levels (or activity) >50U/dL are recommended for birth, neuraxial analgesia, and 3-7 days post-partum.(4) Desmopressin, which releases endogenous VWF, or VWF containing concentrates can be administered to increase VWF levels.(5)
Rare bleeding disorders include disorders of prothrombin, fibrinogen, Factor V, VII, X, XI, XIII and functional platelet disorders. There is limited data to guide management of these woman. In many, pregnancy does not improve the bleeding risk(3) and factor replacement is achieved with transfusion of plasma, factor concentrates or platelets.(5)
Objective
We aim to describe the characteristics and outcomes of pregnancies and births of a cohort of Australian women with IBD.
Methods
All women with a known history of an IBD, who received care throughout their pregnancy or birth at either Prince of Wales Hospital Sydney, The Royal Hospital for Women Sydney, Westmead Hospital Sydney, John Hunter Hospital Newcastle, Calvary Mater Newcastle, Royal Women’s Hospital Melbourne and Joan Kirner Women’s and Children’s at Sunshine Hospital Melbourne between 2011 and 2020 were included. Ethics approval was obtained through the human research ethics committee (SESLHD HREC 15/294).
Data was retrospectively obtained from the patient and neonatal medical records. Descriptive analysis was used to report maternal characteristics, factor levels, factor replacement, pregnancy, birth and neonatal outcomes for each pregnancy. Data analysis was performed using SAS studio.
Funding was not received for this study.
Results:
The study captured 100 women with 132 pregnancies and 134 live births
Figure 1 demonstrates the normalisation of mean VWF levels in women with Type 1 VWD (VWF antigen level) compared to women with Type 2B and 2N VWD (VWF activity level); and mean factor levels in women with mild HA compared to mild HB, FXI deficiency and hypofibrinogenaemia. The mean factor levels for both HA and HB carriers were above recommended levels throughout all stages of pregnancy.