PB0478 - Changes in circulating H3 Histone levels during Extracorporeal Membrane Oxygenation in patients with severe respiratory failure with correlation to haemostatic complications

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Andrew J. Doyle, MBChB MRCP FRCPath

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

Co-Author(s)

KP

Kiran Parmar

Biomedical Scientist
Guy's & St Thomas NHS Foundation Trust
London, England, United Kingdom
AA

Andrew Aswani

Consultant Intensivist
Guy's & St Thomas NHS Foundation Trust
London, England, United Kingdom
Karen A. Breen, MD

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

Nicholas A. Barrett

Consultant Intensivist
Guy's & St Thomas NHS Foundation Trust
London, England, United Kingdom
AR

Andrew Retter

Consultant Intensivist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom
Beverley J. Hunt, MD, FRCP, FRCPath

Professor of Thrombosis & Haemostasis, Consultant Haematologist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom

Background: Circulating histones are part of damage associate molecular pattern of lung injury. They are also recognised as contributing to a prothrombotic tendency and thrombocytopenia. However, their role during extracorporeal membrane oxygenation (ECMO) has not been described.

Aims: 1) To assess changes in circulating H3.1 and citrullinated H3 (H3R8) levels, a marker of NETosis, in patients requiring veno-venous ECMO 2) To correlate H3 with haemostatic events and thrombocytopenia

Methods: Blood samples were taken from 17 patients >18 years old at a single, high-volume ECMO centre. Samples were taken at pre-ECMO, 1-hour, 1-day, 2-days, pre-decannulation and 1-day after. Samples were analysed by ELISA for H3.1 and H3R8 according to manufacturer’s protocols (Volition, Belgium). Ethical approval was gained for the study with nominated consultee consent for patient samples.

Results: H3.1 (reference range 0-48ng/mL) was significantly elevated prior to cannulation and continued to increase during the first 2 days (median 1271 to 1924ng/mL, p=0.031). There was a similar increase in H3R8 (reference range 0-4.7ng/mL) following the first 2 days (49.6 to 123.9ng/mL, p=0.012) however H3.1/H3R8 ratio remained stable (19.7 to 12.5, p=0.26). There was a decrease from preceding to decannulation to 1-day after in H3.1 (1321 to 953ng/mL, p=0.030) and H3R8 (58.2 to 36.0ng/mL, p=0.01).

There was no significant difference in H3 levels in patients with pulmonary embolism, requiring circuit change, intracranial haemorrhage, or deep vein thrombosis compared to those without. There was no difference in H3.1 levels 24- and 48-hours preceding the development of thrombocytopenia after 2-days of ECMO.

Conclusion(s): These results suggest a combination of both lung injury and extracellular damage by the ECMO circuit contributing to high levels of circulating H3 histones. There was a lack of correlation between H3 histones to haemostatic events and thrombocytopenia, although given their highly elevated levels, it does not exclude their pathological role.