Effects of cupric chloride on coagulation in human plasma: role of fibrinogen

Vance G Nielsen, Timothy D. Ward, Paul M. Ford

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: Copper poisoning is associated with severe multiorgan injury and potentially death if chelation therapy is not administered. Of interest, while important gastrointestinal and urinary tract hemorrhage is associated with copper poisoning, very little is known concerning the nature of copper induced coagulopathy. Methods: Using thrombelastography, we assessed changes in coagulation kinetics in human plasma following exposure to copper concentrations encountered during poisoning. Results: While time to commence coagulation was not compromised, both velocity of thrombus growth and final strength were diminished. This result was duplicated with one concentration of copper in factor XIII deficient plasma. This pattern of coagulation kinetic response was interpreted as copper mediated fibrinogen dysfunction, perhaps via oxidation of key fibrinogen disulfide bridges. Lastly, experiments wherein glutathione was added implicated copper generated radical oxygen species as one of the mechanisms responsible for compromised coagulation kinetics. Conclusions: While chelation therapy is the key to survival following copper poisoning, perhaps this and future investigations of how copper affects coagulation may provide insight into effective supportive therapy for patients with active bleeding.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
DOIs
StateAccepted/In press - Jun 21 2018

Fingerprint

Fibrinogen
Copper
Poisoning
Chelation Therapy
Hemorrhage
Thrombelastography
Factor XIII
cupric chloride
Urinary Tract
Disulfides
Glutathione
Gastrointestinal Tract
Reactive Oxygen Species
Thrombosis
Survival
Wounds and Injuries
Growth

Keywords

  • Copper poisoning
  • Factor XIII
  • Fibrinogen
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Effects of cupric chloride on coagulation in human plasma : role of fibrinogen. / Nielsen, Vance G; Ward, Timothy D.; Ford, Paul M.

In: Journal of Thrombosis and Thrombolysis, 21.06.2018, p. 1-6.

Research output: Contribution to journalArticle

@article{662a6f1795034e4fb1913cf3fd36218d,
title = "Effects of cupric chloride on coagulation in human plasma: role of fibrinogen",
abstract = "Introduction: Copper poisoning is associated with severe multiorgan injury and potentially death if chelation therapy is not administered. Of interest, while important gastrointestinal and urinary tract hemorrhage is associated with copper poisoning, very little is known concerning the nature of copper induced coagulopathy. Methods: Using thrombelastography, we assessed changes in coagulation kinetics in human plasma following exposure to copper concentrations encountered during poisoning. Results: While time to commence coagulation was not compromised, both velocity of thrombus growth and final strength were diminished. This result was duplicated with one concentration of copper in factor XIII deficient plasma. This pattern of coagulation kinetic response was interpreted as copper mediated fibrinogen dysfunction, perhaps via oxidation of key fibrinogen disulfide bridges. Lastly, experiments wherein glutathione was added implicated copper generated radical oxygen species as one of the mechanisms responsible for compromised coagulation kinetics. Conclusions: While chelation therapy is the key to survival following copper poisoning, perhaps this and future investigations of how copper affects coagulation may provide insight into effective supportive therapy for patients with active bleeding.",
keywords = "Copper poisoning, Factor XIII, Fibrinogen, Thrombelastography",
author = "Nielsen, {Vance G} and Ward, {Timothy D.} and Ford, {Paul M.}",
year = "2018",
month = "6",
day = "21",
doi = "10.1007/s11239-018-1704-4",
language = "English (US)",
pages = "1--6",
journal = "Journal of Thrombosis and Thrombolysis",
issn = "0929-5305",
publisher = "Springer Netherlands",

}

TY - JOUR

T1 - Effects of cupric chloride on coagulation in human plasma

T2 - role of fibrinogen

AU - Nielsen, Vance G

AU - Ward, Timothy D.

AU - Ford, Paul M.

PY - 2018/6/21

Y1 - 2018/6/21

N2 - Introduction: Copper poisoning is associated with severe multiorgan injury and potentially death if chelation therapy is not administered. Of interest, while important gastrointestinal and urinary tract hemorrhage is associated with copper poisoning, very little is known concerning the nature of copper induced coagulopathy. Methods: Using thrombelastography, we assessed changes in coagulation kinetics in human plasma following exposure to copper concentrations encountered during poisoning. Results: While time to commence coagulation was not compromised, both velocity of thrombus growth and final strength were diminished. This result was duplicated with one concentration of copper in factor XIII deficient plasma. This pattern of coagulation kinetic response was interpreted as copper mediated fibrinogen dysfunction, perhaps via oxidation of key fibrinogen disulfide bridges. Lastly, experiments wherein glutathione was added implicated copper generated radical oxygen species as one of the mechanisms responsible for compromised coagulation kinetics. Conclusions: While chelation therapy is the key to survival following copper poisoning, perhaps this and future investigations of how copper affects coagulation may provide insight into effective supportive therapy for patients with active bleeding.

AB - Introduction: Copper poisoning is associated with severe multiorgan injury and potentially death if chelation therapy is not administered. Of interest, while important gastrointestinal and urinary tract hemorrhage is associated with copper poisoning, very little is known concerning the nature of copper induced coagulopathy. Methods: Using thrombelastography, we assessed changes in coagulation kinetics in human plasma following exposure to copper concentrations encountered during poisoning. Results: While time to commence coagulation was not compromised, both velocity of thrombus growth and final strength were diminished. This result was duplicated with one concentration of copper in factor XIII deficient plasma. This pattern of coagulation kinetic response was interpreted as copper mediated fibrinogen dysfunction, perhaps via oxidation of key fibrinogen disulfide bridges. Lastly, experiments wherein glutathione was added implicated copper generated radical oxygen species as one of the mechanisms responsible for compromised coagulation kinetics. Conclusions: While chelation therapy is the key to survival following copper poisoning, perhaps this and future investigations of how copper affects coagulation may provide insight into effective supportive therapy for patients with active bleeding.

KW - Copper poisoning

KW - Factor XIII

KW - Fibrinogen

KW - Thrombelastography

UR - http://www.scopus.com/inward/record.url?scp=85048794204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048794204&partnerID=8YFLogxK

U2 - 10.1007/s11239-018-1704-4

DO - 10.1007/s11239-018-1704-4

M3 - Article

C2 - 29931617

AN - SCOPUS:85048794204

SP - 1

EP - 6

JO - Journal of Thrombosis and Thrombolysis

JF - Journal of Thrombosis and Thrombolysis

SN - 0929-5305

ER -