Amyloid-Fibrinogen Aggregates ("Microclots") Predict Risks of Disseminated Intravascular Coagulation and Mortality.

Schofield, Jeremy ORCID: 0000-0003-2761-913X, Abrams, Simon Timothy ORCID: 0000-0003-3949-2455, Jenkins, Rosalind, Lane, Steven, Wang, Guozheng ORCID: 0000-0001-5525-3548 and Toh, Cheng-Hock (2024) Amyloid-Fibrinogen Aggregates ("Microclots") Predict Risks of Disseminated Intravascular Coagulation and Mortality. Blood advances, 8 (10). bloodadvances.2023012473-bloodadvances.2023012473. ISSN 2473-9529, 2473-9537

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Abstract

Microclots have been associated with various conditions, including post-acute sequelae of SARS-CoV-2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine for their possible clinical utility, blood samples were collected for the first 96 hours from critically ill patients (n=104) admitted to the intensive care unit (ICU). Detection was by staining platelet-poor plasma samples with Thioflavin T and visualized by fluorescent microscopy. Image J software was trained to identify and quantify microclots, which were detected in 44 [42.3%] patients on ICU admission but not in the remaining 60 [57.7%] or in 20 healthy controls [0.0%]. Microclots on admission to ICU were associated with a primary diagnosis of sepsis (microclots present in sepsis=23/44 [52.3%] vs microclots absent in sepsis=19/60 [31.7%], P=0.044). Multicolour immunofluorescence demonstrated that microclots consisted of amyloid-fibrinogen aggregates, which was supported by proteomic analysis. Patients with either a high number or larger-sized microclots had a higher likelihood of developing disseminated intravascular coagulation (DIC) (OR=51.4 [95% CI=6.3-6721.1], P<0.001) and had an increased probability of 28-day mortality (OR=5.3 [95% CI=2.0-15.6], P<0.001). This study concludes that microclots, as defined by amyloid-fibrin(ogen) aggregates, are potentially useful in identifying sepsis and predicting adverse coagulopathic and clinical outcomes.

Item Type:	Article
Uncontrolled Keywords:	Humans, Sepsis, Disseminated Intravascular Coagulation, Critical Illness, Amyloid, Fibrinogen, Prognosis, Aged, Middle Aged, Female, Male, Protein Aggregates, Biomarkers, COVID-19, SARS-CoV-2
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	25 Mar 2024 11:19
Last Modified:	28 Feb 2026 01:15
DOI:	10.1182/bloodadvances.2023012473
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179876
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