The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis

Protty, Majd B., Jenkins, P. Vince, Collins, Peter W. ORCID: https://orcid.org/0000-0002-6410-1324 and O'Donnell, Valerie B. ORCID: https://orcid.org/0000-0003-4089-8460 2022. The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis. Open Biology 12 (4) , 210318. 10.1098/rsob.210318

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Abstract

Phospholipids (PLs) are found in all cell types and are required for structural support and cell activation signalling pathways. In resting cells, PLs are asymmetrically distributed throughout the plasma membrane with native procoagulant aminophospholipids (aPLs) being actively maintained in the inner leaflet of the membrane. Upon platelet activation, aPLs rapidly externalize to the outer leaflet and are essential for supporting the coagulation cascade by providing binding sites for factors in the cell-based model. More recent work has uncovered a role for enzymatically oxidized PLs (eoxPLs) in facilitating coagulation, working in concert with native aPLs. Despite this, the role of aPLs and eoxPLs in thrombo-inflammatory conditions, such as arterial and venous thrombosis, has not been fully elucidated. In this review, we describe the biochemical structures, distribution and regulation of aPL externalization and summarize the literature on eoxPL generation in circulating blood cells. We focus on the currently understood role of these lipids in mediating coagulation reactions in vitro, in vivo and in human thrombotic disease. Finally, we highlight gaps in our understanding in how these lipids vary in health and disease, which may place them as future therapeutic targets for the management of thrombo-inflammatory conditions.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/
Publisher:	The Royal Society
ISSN:	2046-2441
Funders:	Wellcome Trust, BHF
Date of First Compliant Deposit:	5 May 2022
Date of Acceptance:	21 February 2022
Last Modified:	28 Feb 2024 02:07
URI:	https://orca.cardiff.ac.uk/id/eprint/149464

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