Vance G Nielsen1, Timothy D Ward2, Paul M Ford2. 1. Department of Anesthesiology, The University of Arizona College of Medicine, P.O. Box 245114, 1501 North Campbell Avenue, Tucson, AZ, 85724-5114, USA. vgnielsen333@gmail.com. 2. Department of Anesthesiology, The University of Arizona College of Medicine, P.O. Box 245114, 1501 North Campbell Avenue, Tucson, AZ, 85724-5114, USA.
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.
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 fibrinogendisulfide 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.
Authors: Vance G Nielsen; Paul Audu; Lana Cankovic; Ralph T Lyerly; Brad L Steenwyk; Valerie Armstead; Garry Powell Journal: Anesth Analg Date: 2007-01 Impact factor: 5.108
Authors: Vance G Nielsen; S Nini Malayaman; Ejaz S Khan; James K Kirklin; James F George Journal: Blood Coagul Fibrinolysis Date: 2010-06 Impact factor: 1.276