Bβ 14 Arg→Cys variant dysfibrinogen and its association with thrombosis

Analysis of plasmin generation and clot lysis of plasma fibrinogen purified from a heterozygous dysfibrinogenemia, BβGly15Cys (Hamamatsu II)

“…Additionally, in vitro studies with the AR554C fibrinogen have demonstrated that impaired fibrinolysis, thinner and many branched fibers, increased clot stiffness, and an increased cross-linking potential probably explain the thrombosis and embolism seen in the families afflicted [22,[27][28][29][30]. It is interesting that for the BArg14Cys variants, which are the immediate vicinity of BGly15 residue and with a potential albumin binding (demonstrated in the propositus of Ijmuiden [12]; however, no others have been analyzed), severe thrombosis such as deep venous thrombosis, pulmonary embolism, or cerebral infarction has been reported in 6 out of the 8 families [4, [10][11][12][13][14][15][16]. Of the four previously found heterozygous BGly15Cys variants, which were positive for the albumin binding form, only the Kosai propositus [6,7] suffered from arteriosclerosis obliterans, and no history of thrombosis was reported among the members of the Ogasa [6,7], Ise [8], or Fukuoka II [9] families.…”

“…It is interesting that no BGly15Cys variant has ever been reported outside of Japan. Only the Kosai propositus out of the four heterozygous BGly15Cys variants suffered from arteriosclerosis obliterans, and no history of thrombosis or bleeding tendency was reported among the members of the four families; whereas, in 6 out of the 8 families with the BArg14Cys variant, which is the immediate vicinity of BGly15 residue and with a potential albumin binding, severe thrombosis (such as deep venous thrombosis, pulmonary embolism, or cerebral infarction) has been reported [4, [10][11][12][13][14][15][16]. Recently, we also found a new heterozygous dysfibrinogenemia, designated as Hamamatsu II, which is a BGly15Cys variant in a patient who suffered from an infarction of the medulla oblongata (Wallenberg syndrome).…”

Accurate testing for dysfunctional molecules: the potential for missing the diagnosis

“…, 2010). Abnormal fibrinogen molecules causing hypercoagulability (decreased plasmin cleavage or stronger polymerization) may be present but again, the standard fibrinogen assay is not able to elucidate these types of defects (Castaman et al. , 2005).…”

A Bβ 14 Arg → Cys fibrinogen variant in a patient with thrombotic complications (fibrinogen St‐Germain III)

“…This case is the first B β 14 Arg → Cys mutation reported in a French family. Six other cases of dysfibrinogenemia related to the B β 14 Arg → Cys mutation have been reported in unrelated families [4–9]. Among them, no case was associated with bleeding complications and only one was asymptomatic [4].…”

“…Fibrinogen Christchurch III was described in a patient with PE at the age of 19 and superficial thrombophlebitis at the age of 29, and a severe venous thrombosis history was reported in the family [6–7]. Fibrinogens London VIII and Vicenza III were reported in two families, with clear cosegregation of the dysfibrinogen, the mutation and thrombosis [8–9].…”