Dr Bethan Goulden1, Dr Charlotte Frise2, Ms Clare Luby3, Dr Louise Page3
1University College London, London, United Kingdom, 2Queen Charlotte’s and Chelsea Hospital, , United Kingdom, 3Maternity and Newborn Safety Investigation (MNSI) programme, , United Kingdom
Biography:
Louise Page is a Consultant Obstetrician at West Middlesex Hospital, and Interim Clinical Director of the Maternity and Newborn Safety Investigations (MNSI) programme. MNSI is part of a national strategy to improve maternity safety in the NHS in England through the investigation of patient safety incidents, neonatal and maternal deaths.
Abstract:
Background: Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory sepsis-like syndrome with persistent fever which ultimately progresses to multi-organ dysfunction and death. Triggers include infection, malignancy and autoimmunity. It is treated with immunosuppression.
We present common themes from two maternal deaths secondary to HLH investigated by England’s Maternity and Newborn Safety Investigation (MNSI) programme.
Cases: Both women died of HLH in the context of underlying autoimmune rheumatic disease (AIRD). Shared themes were late diagnoses of HLH and concerns regarding immunosuppression in the context of a sepsis-like illness. Their deaths predated publication of adult HLH guidelines but – whilst neither was referred – occurred following the establishment of a national HLH MDT. HLH was suggested on both occasions by a rheumatologist on the basis of known AIRD – raising the possibility that other women with HLH due to alternative triggers are being missed.
Recommendations:
For clinicians:
1. Think beyond sepsis in the critically unwell febrile mother – screen for HLH using the three Fs (Fever, Falling cell counts, and hyperFerritinaemia)
2. Hesitancy in utilising immunosuppression delays care – seek support (e.g. national HLH MDT)
For investigators:
1. Explore whether non-bacterial causes were considered in women dying of “sepsis”
2. Anchoring bias may occur – a team continues to manage the case as bacterial sepsis despite continued deterioration
a. Do staff feel empowered to question the diagnosis?
b. Do teams have formal de-biasing strategies in place (e.g. internal MDT, route for seeking external opinion)?
3. Evaluate for HLH retrospectively by examining observation charts, laboratory parameters (e.g. cell counts, ferritin), biopsies and imaging (e.g. hepatosplenomegaly).
Summary: The exact prevalence of pregnancy associated HLH is unknown and may be underdiagnosed. Investigating bodies should be alert to the possibility of HLH as the true cause of death in any woman who dies of a sepsis-like syndrome.
Keywords
Maternal mortality, haemophagocytic lymphohistiocytosis, sepsis
References
1. Thompson A, Banerjee S, Churchill D, Knight M. Haemophagocytic lymphohistiocytosis in pregnancy and the postpartum period: A retrospective case series analysis. NIHR Open Res 2023;3:12. https://doi.org/10.3310/nihropenres.13339.1.
2. Cox MF, Mackenzie S, Low R, Brown M, Sanchez E, Carr A, et al. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline. The Lancet Rheumatology 2024;6:e51–62. https://doi.org/10.1016/S2665-9913(23)00273-4.