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The Tissue Factor Expression of Monocyte Subsets and the Activation of Coagulation during Human Endotoxaemia

1Newcastle University, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom, 2Newcastle upon Tyne Hospitals NHS Foundation Trust, Haematology, Newcastle upon Tyne, United Kingdom, 3Newcastle upon Tyne Hospitals NHS Foundation Trust, Respiratory Medicine, Newcastle upon Tyne, United Kingdom, 4Maastricht University Medical Center, Thrombosis Expertise Center and CARIM school for Cardiovascular Diseases, Maastricht, the Netherlands, 5City Hospitals Sunderland NHS Foundation Trust, Anaesthesia and Intensive Care Medicine, Sunderland, United Kingdom

Abstract Number: PB1987

Meeting: ISTH 2020 Congress

Theme: Vascular Biology » Inflammation and Sepsis

Background: Monocytic surface expression of tissue factor (TF) is implicated in the development of sepsis-associated coagulopathy. Monocytes are divided into three subsets: classical, intermediate and non-classical.

Aims: This work investigates the surface TF expression between monocyte subsets during endotoxaemia.

Methods: Lipopolysaccharide (LPS, 1ng/kg) was administrated intravenously to healthy volunteers (n= 13). Informed consent was given. Ethical approval was granted by a medical ethics committee. Blood samples were taken at baseline, 1.5, 4, 6, 10, and 24 hours, and 7 days following LPS injection. Whole blood flow cytometry was used to measure monocytic TF surface expression. Markers of activated coagulation were measured at CARIM with in-house constructed ELISA’s to quantify complexes between factor (F) XIa, FIXa, FXa or thrombin with antithrombin (AT), or FXIIa in complex with C1 esterase inhibitor (C1inh).

Results: Two types of TF response were identified: 8 participants had an increase in monocytic TF surface expression (responders), the remaining 5 had no change in TF (non-responders). Responses were consistent across each monocyte subset. Intermediate and non-classical monocytes expressed higher levels of surface TF compared to classical, although endotoxaemia induced a profound transient monocytopenia. Classical monocytes returned at 4 hours and intermediate and non-classical returned at 24 hours (Figure 1).
All participants post LPS injection, had activation of coagulation with elevated levels of thrombin-anti-thrombin and complexes between anti-thrombin and activated factors: IX, X and XI. There was no activation of FXII, assessed by means of the FXIIa:C1inh complex (Figure 2). Coagulation was similarly activated in both responders and non-responders.

Conclusions: Two groups were identified following endotoxaemia, responders who had an increase in monocytic TF surface expression and non-responders who did not. The TF surface response does not affect the activation of coagulation. Further work should investigate whether the marked variation of TF surface expression between individuals can alter the thromboinflammatory response.


[Figure 1: Monocyte subset TF surface expression. Significance was calculated used Friedman’s and Dunn’s post hoc test (*=p<0.05).]


[Figure 2: Markers of coagulation. Significance calculated used Friedman’s and Dunn’s post hoc test (*=p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001).]

To cite this abstract in AMA style:

Musgrave K, Scott J, Sendama W, Spronk HMH, van Oerle R, ten Cate H, Kesteven P, Ruchaud-Sparagano M-, Rostron A, Simpson AJ. The Tissue Factor Expression of Monocyte Subsets and the Activation of Coagulation during Human Endotoxaemia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-tissue-factor-expression-of-monocyte-subsets-and-the-activation-of-coagulation-during-human-endotoxaemia/. Accessed December 10, 2023.

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