OC 51.2 - Changes in VWF, ADAMTS13, and Complement in Preeclampsia, HELLP syndrome and Other Obstetric Complications: a Single Centre Observational Study.

Tuesday, July 12, 2022

11:00 AM – 11:15 AM

Location: ExCel Center, S11A

Presentation Format: Virtual

Presenting Author(s)

Lucy Neave, MBBS MRCP FRCPath

Clinical Research Fellow
UCLH Hospitals NHS Trust / Haemostasis Research Unit, University College London
London, England, United Kingdom

Co-Author(s)

Mari Thomas, MD, PhD

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom
Rd

Rens de Groot

Senior Research Fellow
University College London
London, England, United Kingdom
Andrew J. Doyle, MBChB MRCP FRCPath

Consultant Haematologist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom
AD

Anna L. David

Professor of Obstetrics and Maternal Fetal Medicine
Elizabeth Garrett Anderson Institute for Women's Health, Univerisity College London
London, England, United Kingdom
KM

Katarzyna Maksym

Clinical Research Fellow
Fetal Medicine Unit, UCLH Hospitals NHS Trust /Institute for Women's Health, University College London
London, England, United Kingdom
MW

Melissa Whitten

Consultant in Maternal and Fetal Medicine
Elizabeth Garrett Anderson Institute for Women's Health
London, England, United Kingdom
Marie Scully, MD

Professor of Haemostasis and Thrombosis
Department of Haematology, University College London Hospitals, London, UK
London, England, United Kingdom

Background: There is evidence, some conflicting, of changes in the VWF/ADAMTS13 axis, and also in the complement system, in preeclampsia and HELLP syndrome. Other obstetric complications are less studied in this regard.

Aims: To assess changes in VWF, ADAMTS13 and complement in preeclampsia, HELLP syndrome, fetal growth restriction (unexplained or uteroplacental), and new onset thrombocytopenia ( < 75x109/L), compared to normal pregnancies.

Methods: Pregnant women with a current or previous history of the obstetric complications of interest were recruited at a regional centre, in addition to gestational age-matched normal pregnant controls. ADAMTS13 activity, VWF antigen and activity, CH50, and sC5b-9 were measured in blood samples taken at recruitment. Clinical data was collected. Informed consent and regional ethics committee approval (18/NW/0552) were obtained. Data is summarised as median (range). Mann-Whitney was used to compare groups (with significance level P< 0.05).

Results: 128 cases were analyzed. Comparing preeclampsia/HELLP (N=42) with normal pregnancy (N=48) (Table 1), ADAMTS13 activity was significantly lower in preeclampsia, VWF antigen and activity were significantly higher, and the VWF antigen:ADAMTS13 ratio was even higher (3.7 (1.9-6.5) vs 2.1 (0.9-4.7), P< 0.0001). sC5b-9 was higher in preeclampsia/HELLP than normal pregnancy (268 (162-628) vs 189 (110-290), P< 0.0001), but there was no change in CH50. Abnormalities were greater in cases with features of HELLP (N=9). Similar changes were not observed in fetal growth restriction (N=13), thrombocytopenia (N=10), or in pregnant women with a history of preeclampsia (N=15) (Figure 1). The odds of VWF Ag:ADAMTS13 ratio > 2 was 31.9 times higher in preeclampsia than normal pregnancy (95% CI 4.8-338.4), while the odds of sC5b-9>180ng/ml was 11.0 times higher (2.6-49.7).

Conclusion(s): There is marked elevation in VWF levels, VWF antigen:ADAMTS13 ratio, and sC5b-9 in preeclampsia/HELLP compared to normal pregnancies and certain other obstetric complications. This may result from endothelial activation, and may have potential therapeutically and diagnostically.