Low Maternal Plasma Fibrinogen

Key Points

  • Obstetric haemorrhage remains an important cause of maternal mortality in the UK.
  • Evidence suggests the incidence of obstetric haemorrhage in high-resource settings is increasing
  • It is unclear whether fibrinogen replacement at or below a level of 2g/L affects blood loss
  • Further observational evidence is required before potentially developing a randomised controlled trial of coagulation management.

Surveillance Period

1st November 2017 – 31st October 2018

Background

Obstetric haemorrhage is an important cause of maternal mortality in the UK. In the most recent Confidential Enquiry (2012-14) thirteen women died as a direct consequence of haemorrhage; a number that is unchanged from the previous report [1]. With evidence suggesting that the incidence of obstetric haemorrhage is increasing in high-resource settings, a better understanding of the mechanisms of injury and, more importantly, the clinical sequelae in obstetric patients is needed [2-4].

Women with a plasma fibrinogen <2 g/L and continuing bleeding represent a high-risk group that is associated with both progressive haemorrhage and the increased use of blood products and invasive procedures [2, 3]. Two double-blind RCTs have investigated the role of fibrinogen replacement in PPH. Pre-specified subgroup analysis of the second RCT showed that, if the fibrinogen level was >2 g/L during severe PPH, fibrinogen replacement did not affect blood loss or the need for transfusion but that an effect below 2 g/L could not be excluded [6]. This supports a RCOG recommendation that fibrinogen replacement is not necessary if plasma fibrinogen is above 2 g/L [2]. However, a possible effect of fibrinogen replacement at fibrinogen levels of below 2 g/l cannot be excluded on the basis of the trial data [5, 6].

It is clear from the previous UKOSS study of massive transfusion [4] that the haematological parameters observed amongst groups of women with different causes for their obstetric haemorrhage are very variable, and hence differences in the underlying causes of haemorrhage in the trial participants may have had a substantial impact. The aim of this study is to obtain further observational evidence before potentially developing a randomised controlled trial of coagulation management.

Objective

To use the UK Obstetric Surveillance System (UKOSS) to describe:

  1. The incidence and causes of low maternal plasma fibrinogen concentrations;
  2. The demographic and antenatal characteristics of these women;
  3. The management of low maternal fibrinogen concentration;
  4. The outcomes for women and their infants.

Research Questions

  • What is the current incidence of low maternal plasma fibrinogen concentration in the UK?
  • What are the antenatal characteristics of women with low maternal plasma fibrinogen concentrations in the UK?
  • How are women with low maternal plasma fibrinogen concentrations managed?
  • What are the maternal and infant outcomes in women with low maternal plasma fibrinogen concentration?

Case Definition

Any woman with either a laboratory Clauss fibrinogen <2g/L OR a derived fibrinogen <2g/L OR Fibtem <10 mm OR TEG functional fibrinogen <200 mg/dL at any time during pregnancy or postpartum before first discharge, irrespective of cause.

Funding

This study is being funded as part of the programme of the Policy Research Unit in Maternal Health and Care. 

Ethics Committee Approval

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

Lead Investigator

Marian Knight, NPEU
Simon Stanworth, NHSBT
Rachel Collis, Cardiff and Vale UHB
Peter Collins, Cardiff and Vale UHB

References

[1] Knight, M., et al., MBRRACE-UK: Saving Lives, Improving Mother’s Care - Surveillance of maternal deaths in the UK 2012-14 and lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009-14. 2016, National Perinatal Epidemiology Unit, University of Oxford: Oxford.
[2] Prevention and Management of Postpartum Haemorrhage: Green-top Guideline No. 52. BJOG, 2017. 124(5): p. e106-e149.
[3] Knight, M., et al., Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth, 2009. 9: p. 55.
[4] Green, L., et al., The epidemiology and outcomes of women with postpartum haemorrhage requiring massive transfusion with eight or more units of red cells: a national cross-sectional study. BJOG, 2015.
[5] Collins, P.W., et al., Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study. Br J Anaesth, 2017. 119(3): p. 422-434.
[6] Collins, P.W., et al., Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. Br J Anaesth, 2017. 119(3): p. 411-421.