Acute obstetric coagulopathy is associated with excess plasmin generation and proteolysis of fibrinogen and factor V

Collins, Peter W. ORCID: https://orcid.org/0000-0002-6410-1324, Whyte, Claire S., de Lloyd, Lucy, Narwal, Anuj, Bell, Sarah F., Gill, Nicholas, Collis, Rachel E., Jenkins, Peter V. and Mutch, Nicola J. 2025. Acute obstetric coagulopathy is associated with excess plasmin generation and proteolysis of fibrinogen and factor V. Blood Advances 10.1182/bloodadvances.2024015514

PDF - Published Version Download (1MB)

Abstract

Haemostatic impairment may exacerbate postpartum haemorrhage (PPH). Previously, we described a distinct coagulopathy, associated with multiple causes of PPH including placental abruption and amniotic fluid embolus, termed acute obstetric coagulopathy (AOC). AOC is characterised by very high plasmin/antiplasmin complexes and rapid depletion of functional fibrinogen and factor (F)V. To determine mechanisms underlying AOC we investigated plasma from 12 women with AOC (here defined as plasmin/antiplasmin >25,000 ng/mL) and 21 severe PPH (measured blood loss >2000 mL or placental abruption) without AOC (plasmin/antiplasmin <25,000 ng/mL). Plasma from patients with AOC had a 4-fold increased ability to generate plasmin compared to severe PPH without AOC (p<0.0002). AOC was strongly associated with fibrinogen cleavage in the circulation, demonstrated by fragment D and other breakdown products on Western blot, (p<0.0001). D-dimer were increased 36-fold in AOC compared to severe PPH without AOC but thrombin/antithrombin complexes were not raised. FV was reduced on Western blot in AOC but not severe PPH without AOC (p<0.001) suggesting FV cleavage. Confocal microscopy showed similar clot structure between AOC and non-AOC samples but both groups differed from non-bleeding pregnant controls. These data suggest that in AOC an excess of plasmin cleaves fibrinogen and FV in the circulation causing a specific, pathognomonic depletion of coagulation factors. Fibrin(ogen) breakdown products have cofactor function for tissue plasminogen activator and these data are consistent with these breakdown products enhancing plasmin generation and potentially driving aberrant plasmin generation in AOC. These results have implications for the clinical management of coagulopathy during PPH.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2025-02-06
Publisher:	American Society of Hematology (ASH Publications)
ISSN:	2473-9529
Date of First Compliant Deposit:	18 February 2025
Date of Acceptance:	27 January 2025
Last Modified:	18 Feb 2025 12:00
URI:	https://orca.cardiff.ac.uk/id/eprint/176284

Actions (repository staff only)

Edit Item