title: Severe bleeding in a woman heterozygous for the fibrinogen gammaR275C mutation.
abstract: The dysfibrinogen gammaR275C can be a clinically silent mutation, with only two out of 17 cases in the literature reporting a hemorrhagic presentation and four cases reporting a thrombotic presentation. We describe here a particularly severe presentation in 54-year-old female patient who required a hysterectomy at 47 years of age due to heavy menstrual bleeding. Coagulation studies revealed a prolonged prothrombin time and thrombin time, a normal fibrinogen antigen level, and a low fibrinogen activity level. Molecular analysis of the patient's DNA revealed a gamma chain gene mutation resulting in an amino acid substitution at residue 275 (gammaR275C). Protein sequencing of the fibrinogen gamma chain confirmed this mutation, which was named Fibrinogen Portland I. This case demonstrates that the gammaR275C mutation can lead to a severe hemorrhagic phenotype.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, USA.
authors.forename: Chantelle M
authors.initials: CM
authors.lastname: Rein
authors.forename: Brian L
authors.initials: BL
authors.lastname: Anderson
authors.forename: Morgan M
authors.initials: MM
authors.lastname: Ballard
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Domes
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Johnston
authors.forename: Russell Jared
authors.initials: RJ
authors.lastname: Madsen
authors.forename: Kathryn K M
authors.initials: KK
authors.lastname: Wolper
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Terker
authors.forename: John M
authors.initials: JM
authors.lastname: Strother
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Deloughery
authors.forename: David H
authors.initials: DH
authors.lastname: Farrell
mesh_terms: D019943:Amino Acid Substitution; D001780:Blood Coagulation Tests; D005260:Female; D015241:Fibrinogens, Abnormal / Q000235:genetics* / Q000302:isolation & purification; D006579:Heterozygote; D006801:Humans; D008595:Menorrhagia / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: D015241:Fibrinogens, Abnormal
references.citation: Blood. 1998 Oct 1;92(7):2195-212
references.pmid: 9746756
references.citation: Blood Coagul Fibrinolysis. 1995 May;6(3):198-206
references.pmid: 7654933
references.citation: J Thromb Haemost. 2005 Jul;3(7):1337-48
references.pmid: 15978088
references.citation: Mol Aspects Med. 2008 Aug;29(4):203-54
references.pmid: 18329094
references.citation: J Clin Invest. 1995 Aug;96(2):1053-8
references.pmid: 7635941
references.citation: Arch Pathol Lab Med. 2002 Apr;126(4):499-505
references.pmid: 11900586
references.citation: Nature. 1997 Oct 2;389(6650):455-62
references.pmid: 9333233
references.citation: Blood Coagul Fibrinolysis. 1994 Aug;5(4):463-71
references.pmid: 7841300
references.citation: Proc Soc Exp Biol Med. 1963 Aug-Sep;113:989-94
references.pmid: 14073163
references.citation: Semin Thromb Hemost. 2009 Jun;35(4):356-66
references.pmid: 19598064
references.citation: Br J Haematol. 2006 Jul;134(2):220-6
references.pmid: 16846481
references.citation: Blood. 1994 Sep 15;84(6):1874-80
references.pmid: 8080993
references.citation: Thromb Haemost. 1995 Jan;73(1):151-61
references.pmid: 7740487
references.citation: Curr Opin Hematol. 2007 May;14(3):236-41
references.pmid: 17414213
references.citation: Br J Haematol. 2001 Aug;114(2):249-57
references.pmid: 11529842
references.citation: Ann N Y Acad Sci. 2001;936:89-90
references.pmid: 11460527
references.citation: Thromb Haemost. 2008 Jun;99(6):1008-12
references.pmid: 18521501