Schofield, Jeremy 
ORCID: 0000-0003-2761-913X, Abrams, Simon Timothy, Jenkins, Rosalind, Lane, Steven, Wang, Guozheng and Toh, Cheng-Hock
(2024)
Amyloid-Fibrinogen Aggregates ("Microclots") Predict Risks of Disseminated Intravascular Coagulation and Mortality.
Blood advances.
bloodadvances.2023012473-bloodadvances.2023012473.
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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: | Emerging Infectious Diseases, Clinical Research, Sepsis, Hematology, Prevention, Infectious Diseases, 4 Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Infection |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 25 Mar 2024 11:19 |
| Last Modified: | 10 Apr 2024 09:10 |
| DOI: | 10.1182/bloodadvances.2023012473 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179876 |
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