Abstract
Chronic migraine (CM) is a disabling painful condition that is associated with dementia and thrombotic disease. It has been proposed that carbon monoxide (CO) and iron may play a role in CM, and CO and iron are products of the heme oxygenase system which is widespread within the brain. Further, CO and iron enhance plasmatic coagulation in part via a fibrinogen-dependent mechanism. Thus, our goal was to determine whether patients with CM had experienced carboxyhemefibrinogen formation, iron bound fibrinogen formation and plasmatic hypercoagulability. Nonsmokers with CM were recruited after informed, written consent. Blood was collected, anticoagulated with sodium citrate, and then centrifuged with plasma stored at -80ºC. Carboxyhemefibrinogen formation, iron bound fibrinogen formation and coagulation kinetics were determined via thrombelastographic methods. Patient results were compared with laboratory values generated from normal control plasmas. Incidence (95% confidence intervals) of the various parameters was determined using the Clopper-Pearson method. Twenty-six CM patients (24 female) were recruited; they were 46±12 years old. With regard to fibrinogen modification, 88.5% (69.8%-97.6%) of CM patients had formation of carboxyhemefibrinogen, iron bound fibrinogen, or both. With regard to coagulation, 42.3% (23.4%-63.1%) of patients had abnormally decreased time to clot initiation, 80.8% (60.6%-93.4%) had abnormally large velocity of clot formation, and 46.2% (26.6%-66.7%) had abnormally strong clot strength. Patients with CM have a large incidence of carboxyhemefibrinogen and iron bound fibrinogen formation and hypercoagulability. Confirmatory and potential therapeutic clinical trials targeting CO and iron modified hypercoagulation as a source of pain and vascular disease in CM patients are indicated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1079-1085 |
| Number of pages | 7 |
| Journal | CNS and Neurological Disorders - Drug Targets |
| Volume | 14 |
| Issue number | 8 |
| State | Published - Oct 1 2015 |
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Keywords
- Carbon monoxide
- Fibrinogen
- Iron
- Migraine
- Thrombelastography
- Vascular disease
ASJC Scopus subject areas
- Neuroscience(all)
- Pharmacology
Cite this
Chronic migraineurs form carboxyhemefibrinogen and iron-bound fibrinogen. / Nielsen, Vance G; Kulin, Wendi; Lawall, John Samuel; Macfarland, Felesia Nancy; Chen, Andrew; Hadley, Heidi Adelleen; Dadeppo, Adam James; Steinbrenner, Evangelina Barbara; Matika, Ryan William.
In: CNS and Neurological Disorders - Drug Targets, Vol. 14, No. 8, 01.10.2015, p. 1079-1085.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic migraineurs form carboxyhemefibrinogen and iron-bound fibrinogen
AU - Nielsen, Vance G
AU - Kulin, Wendi
AU - Lawall, John Samuel
AU - Macfarland, Felesia Nancy
AU - Chen, Andrew
AU - Hadley, Heidi Adelleen
AU - Dadeppo, Adam James
AU - Steinbrenner, Evangelina Barbara
AU - Matika, Ryan William
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Chronic migraine (CM) is a disabling painful condition that is associated with dementia and thrombotic disease. It has been proposed that carbon monoxide (CO) and iron may play a role in CM, and CO and iron are products of the heme oxygenase system which is widespread within the brain. Further, CO and iron enhance plasmatic coagulation in part via a fibrinogen-dependent mechanism. Thus, our goal was to determine whether patients with CM had experienced carboxyhemefibrinogen formation, iron bound fibrinogen formation and plasmatic hypercoagulability. Nonsmokers with CM were recruited after informed, written consent. Blood was collected, anticoagulated with sodium citrate, and then centrifuged with plasma stored at -80ºC. Carboxyhemefibrinogen formation, iron bound fibrinogen formation and coagulation kinetics were determined via thrombelastographic methods. Patient results were compared with laboratory values generated from normal control plasmas. Incidence (95% confidence intervals) of the various parameters was determined using the Clopper-Pearson method. Twenty-six CM patients (24 female) were recruited; they were 46±12 years old. With regard to fibrinogen modification, 88.5% (69.8%-97.6%) of CM patients had formation of carboxyhemefibrinogen, iron bound fibrinogen, or both. With regard to coagulation, 42.3% (23.4%-63.1%) of patients had abnormally decreased time to clot initiation, 80.8% (60.6%-93.4%) had abnormally large velocity of clot formation, and 46.2% (26.6%-66.7%) had abnormally strong clot strength. Patients with CM have a large incidence of carboxyhemefibrinogen and iron bound fibrinogen formation and hypercoagulability. Confirmatory and potential therapeutic clinical trials targeting CO and iron modified hypercoagulation as a source of pain and vascular disease in CM patients are indicated.
AB - Chronic migraine (CM) is a disabling painful condition that is associated with dementia and thrombotic disease. It has been proposed that carbon monoxide (CO) and iron may play a role in CM, and CO and iron are products of the heme oxygenase system which is widespread within the brain. Further, CO and iron enhance plasmatic coagulation in part via a fibrinogen-dependent mechanism. Thus, our goal was to determine whether patients with CM had experienced carboxyhemefibrinogen formation, iron bound fibrinogen formation and plasmatic hypercoagulability. Nonsmokers with CM were recruited after informed, written consent. Blood was collected, anticoagulated with sodium citrate, and then centrifuged with plasma stored at -80ºC. Carboxyhemefibrinogen formation, iron bound fibrinogen formation and coagulation kinetics were determined via thrombelastographic methods. Patient results were compared with laboratory values generated from normal control plasmas. Incidence (95% confidence intervals) of the various parameters was determined using the Clopper-Pearson method. Twenty-six CM patients (24 female) were recruited; they were 46±12 years old. With regard to fibrinogen modification, 88.5% (69.8%-97.6%) of CM patients had formation of carboxyhemefibrinogen, iron bound fibrinogen, or both. With regard to coagulation, 42.3% (23.4%-63.1%) of patients had abnormally decreased time to clot initiation, 80.8% (60.6%-93.4%) had abnormally large velocity of clot formation, and 46.2% (26.6%-66.7%) had abnormally strong clot strength. Patients with CM have a large incidence of carboxyhemefibrinogen and iron bound fibrinogen formation and hypercoagulability. Confirmatory and potential therapeutic clinical trials targeting CO and iron modified hypercoagulation as a source of pain and vascular disease in CM patients are indicated.
KW - Carbon monoxide
KW - Fibrinogen
KW - Iron
KW - Migraine
KW - Thrombelastography
KW - Vascular disease
UR - http://www.scopus.com/inward/record.url?scp=84945400017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945400017&partnerID=8YFLogxK
M3 - Article
C2 - 26295816
AN - SCOPUS:84945400017
VL - 14
SP - 1079
EP - 1085
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
SN - 1871-5273
IS - 8
ER -