Fibrinogen Longmont: A Clinically Heterogeneous Dysfibrinogenemia with Discrepant Fibrinogen Results Influenced by Clot Detection Method and Reagent.

Abstract

Fibrinogen is a 340kDa glycoprotein composed of three pairs of polypeptide chains. Thrombin cleaves the N-terminal A α and B β chains, exposing binding sites that enable polymerization and cross-linking to form a fi brin clot. Fibrinogen disorders can be quantitative or qualitative, inherited or acquired. Current International Society on Thrombosis and Haemostasis guidelines recommend a stepwise approach to diagnosis of congenital fi brinogen disorders, involving clot-based activated partial thromboplastin time (APTT) and prothrombin time (PT), and fi brinogen measurement by functional and antigenic assays. 1 Congenital dys fi brinoge-nemias encompass over 400 abnormal variants, typi fi ed by abnormal functional assays with discordant normal antigenic levels. They are clinically diverse and can be asymptomatic or associated with bleeding and thrombotic sequelae. 1 – 3 We report two adult siblings ( ► Table 1 ) diagnosed with the fi brinogen Longmont variant after an unmeasurable Clauss fi brinogen (FibC) was found. Informed consent for publication of this case report was obtained. The 49-year-old female proband human STA-Thrombin. Subsequently, our laboratory validated the use of STA-Thrombin on the ACL TOP and repeated the female patient ’ s FibC, obtaining a normal result. Examination of ammonium sulfate puri fi ed fi brinogen by online reverse-phase electrospray time-of- fl ight mass spectrometry for both patients, suggested heterozygosity for an Arg- > Cys (-53Da) polymorphism in the B β chain. DNA sequencing of exon 4 of FGB con fi rmed that both were heterozygous for fi brinogen Longmont with a point mutation resulting in B β 166Arg- > Cys ( FGB NM_0005141.4:c.586C > T, p.Arg196Cys).