Related Experiment Video
Updated: Jun 30, 2025
Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Microclots, as defined by amyloid-fibrinogen aggregates, predict risks of disseminated intravascular coagulation and
Jeremy Schofield1,2, Simon T Abrams1,3, Rosalind Jenkins4
1Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Abstract:
Microclots have been associated with various conditions, including postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine 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 patients (42.3%) on ICU admission but not in the remaining 60 (57.7%) or the 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 = .044). Multicolor 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 (odds ratio [OR], 51.4; 95% confidence interval [CI], 6.3-6721.1; P < .001) and had an increased probability of 28-day mortality (OR, 5.3; 95% CI, 2.0-15.6; P < .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.
Insights
Microclots, identified as amyloid-fibrinogen aggregates, were found in critically ill patients and associated with sepsis. Their presence and size can predict disseminated intravascular coagulation and mortality risk.
Area of Science:
- Biochemistry
- Hematology
- Critical Care Medicine
Background:
- Microclots, potentially amyloid-fibrinogen aggregates, are linked to various conditions, including post-COVID-19 syndrome.
- Their prognostic value as biomarkers is not well-established.
- Understanding microclot formation and clinical significance is crucial for critically ill patients.
Purpose of the Study:
- To investigate the clinical utility of microclots as prognostic biomarkers in critically ill patients.
- To determine the association between microclots and sepsis, disseminated intravascular coagulation (DIC), and mortality.
- To characterize the composition of microclots.
Main Methods:
- Blood samples were collected from 104 critically ill patients within 96 hours of ICU admission.
- Microclots were detected and quantified in platelet-poor plasma using thioflavin T staining and fluorescent microscopy, aided by Image J software.
- Multicolor immunofluorescence and proteomic analysis were used to determine microclot composition.
Main Results:
- Microclots were detected in 42.3% of ICU patients upon admission, versus 0% in healthy controls.
- Microclot presence on admission was significantly associated with a primary diagnosis of sepsis (P = .044).
- Higher microclot burden (number/size) correlated with increased likelihood of developing DIC (OR, 51.4; P < .001) and higher 28-day mortality (OR, 5.3; P < .001).
Conclusions:
- Microclots, characterized as amyloid-fibrinogen aggregates, are present in a significant portion of critically ill patients.
- Microclot detection can aid in identifying sepsis.
- Microclot presence and burden are valuable indicators for predicting adverse coagulopathic outcomes and mortality in the ICU.
Related Concept Videos
01:16Clot Retraction and Fibrinolysis
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
01:24Disorders of Hemostasis
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
01:09Coagulation
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...