Title:Chronic Migraineurs Form Carboxyhemefibrinogen and Iron-Bound Fibrinogen
Volume: 14
Issue: 8
Author(s): Vance Girard Nielsen, Wendi Kulin, John Samuel LaWall, Felesia Nancy MacFarland, Andrew Chen, Heidi Adelleen Hadley, Adam James DaDeppo, Evangelina Barbara Steinbrenner and Ryan William Matika
Affiliation:
Keywords:
Migraine, fibrinogen, carbon monoxide, iron, thrombelastography, vascular disease.
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.
