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Updated: Jun 25, 2025

Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
05:49

Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets

Published on: November 29, 2024

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Extracellular histones: a unifying mechanism driving platelet-dependent extracellular vesicle release and thrombus

Alicia S Eustes1, Azaj Ahmed1, Jagadish Swamy1

  • 1Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

Journal of Thrombosis and Haemostasis : JTH
|May 30, 2024
PubMed

Insights

Extracellular histones and extracellular vesicles (EVs) drive the prothrombotic state in COVID-19 patients. Targeting histones with therapy may offer a beneficial treatment strategy for reducing thrombosis risk in COVID-19.

Area of Science:

  • Hematology
  • Immunology
  • Infectious Diseases

Background:

  • COVID-19 (Coronavirus disease 2019) is associated with significant inflammation and coagulopathy.
  • The precise mechanisms leading to a prothrombotic state in COVID-19 remain incompletely understood.
  • Elevated extracellular histones in SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infected patients suggest a potential role in thrombosis.

Purpose of the Study:

  • To investigate the hypothesis that platelet activation by extracellular histones is a unifying mechanism for increased thrombin generation and thrombosis in COVID-19.
  • To assess the procoagulant and prothrombotic potential of extracellular histones and extracellular vesicles (EVs) in COVID-19 patients.

Main Methods:

  • Blood samples from hospitalized COVID-19 patients and healthy controls were analyzed.
  • Procoagulant and prothrombotic potential of plasma, extracellular histones, and EVs were measured.
  • Platelet activation, thrombin generation, and thrombus growth were assessed in vitro and in vivo.

Main Results:

  • COVID-19 patients exhibited higher plasma levels of citrullinated histone H3, cell-free DNA, nucleosomes, and EVs compared to controls.
  • COVID-19 plasma enhanced platelet activation, thrombin generation, and thrombus growth, effects inhibited by a histone-neutralizing aptamer.
  • Extracellular vesicles from COVID-19 patients promoted thrombin generation and venous thrombosis.

Conclusions:

  • Extracellular histones and procoagulant EVs are key drivers of the prothrombotic state observed in COVID-19.
  • Therapeutic strategies targeting histones show promise for mitigating thrombosis in COVID-19 patients.
Abstract

Keywords:
COVID-19extracellular vesicleshistonesthrombin generationthrombosis

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