Related Experiment Video
Updated: May 1, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Extracellular histones mediate the effects of metal-rich air particles on blood coagulation
L Cantone1, L Angelici1, V Bollati1
1Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community, Università di Milano and Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Background:
Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated.
Objectives:
In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers.
Methods:
Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and D-dimer. Exposure to PM with aerodynamic diameters <1 μm (PM1) or <10 μm (PM10) and PM10 metal components were estimated for each participant.
Results:
The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (β=107.84, p=0.03), PM10 (β=83.06, p=0.02), and zinc (β=75.14, p=0.03); and a marginal association with iron (β=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (β=0.20, p=0.02; β=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (β=0.13, p=0.03) and iron (β=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (β=0.50, p=0.05) and H3K9ac (β=0.54, p=0.05).
Conclusions:
This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.
More Related Videos
09:41Hemocompatibility Testing of Blood-Contacting Implants in a Flow Loop Model Mimicking Human Blood Flow
Published on: March 5, 2020
09:38A Microfluidic Flow Chamber Model for Platelet Transfusion and Hemostasis Measures Platelet Deposition and Fibrin Formation in Real-time
Published on: February 14, 2017
Related Concept Videos
Extrinsic 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...
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Coagulation
Coagulation
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...
Introduction to Hemostasis
The three phases of hemostasis involve many clotting factors present in plasma and several substances released by platelets and injured tissue cells. It is a fast, localized,...
Acute Inflammation II: Local and Systemic Effects