Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury.
Victims of trauma often develop impaired blood clot formation (coagulopathy) that contributes to bleeding and mortality. Fibrin polymerization is one critical component of clot formation that can be impacted by post-translational oxidative modifications of fibrinogen after exposure to oxidants. In vitro evidence suggests that Aα-C domain methionine sulfoxide formation, in particular, can induce conformational changes that prevent lateral aggregation of fibrin protofibrils during polymerization. We used mass spectrometry of plasma from trauma patients to find that fibrinogen Aα-C domain methionine sulfoxide content was selectively-increased in patients with coagulopathy vs. those without coagulopathy. This evidence supports a novel linkage between oxidative stress, coagulopathy, and bleeding after injury.
University of Washington Division of Emergency Medicine, Harborview Medical Center, Box 359702, 325 9th Avenue, Seattle, WA 98104, USA; Bloodworks Northwest Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102, USA. Electronic address: whiten4@uw.edu.
Nathan J
NJ
White
Bloodworks Northwest Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102, USA.
Yi
Y
Wang
Bloodworks Northwest Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102, USA.
Xiaoyun
X
Fu
Center for Translational Injury Research and Division of Acute Care Surgery, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA.
Jessica C
JC
Cardenas
Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, 410 N 12th Street, P.O. Box 980533, Richmond, VA 23298, USA.
Erika J
EJ
Martin
Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, 410 N 12th Street, P.O. Box 980533, Richmond, VA 23298, USA.
Donald F
DF
Brophy
Center for Translational Injury Research and Division of Acute Care Surgery, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA.
Charles E
CE
Wade
University of Washington Division of Emergency Medicine, Harborview Medical Center, Box 359702, 325 9th Avenue, Seattle, WA 98104, USA.
Xu
X
Wang
University of Washington Division of Emergency Medicine, Harborview Medical Center, Box 359702, 325 9th Avenue, Seattle, WA 98104, USA.
Alexander E
AE
St John
University of Washington Division of Emergency Medicine, Harborview Medical Center, Box 359702, 325 9th Avenue, Seattle, WA 98104, USA.
Esther B
EB
Lim
University of Washington Division of Emergency Medicine, Harborview Medical Center, Box 359702, 325 9th Avenue, Seattle, WA 98104, USA.
Susan A
SA
Stern
Michigan Center for Integrative Research in Critical Care, University of Michigan, Building 10-103A North Campus Research Complex 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Kevin R
KR
Ward
Bloodworks Northwest Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102, USA.
José A
JA
López
Bloodworks Northwest Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102, USA.
Dominic
D
Chung
D000328:Adult; D001777:Blood Coagulation / Q000235:genetics; D005260:Female; D005337:Fibrin / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress; D013927:Thrombosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology
C464794:fibrinogen Aalpha; D005337:Fibrin; D005340:Fibrinogen; D008715:Methionine; C013111:methionine sulfoxide
Coagulopathy; Fibrinogen; Hemorrhage; Methionine sulfoxide; Oxidative stress; Trauma