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

Abstract

In line with our previous report [1], we observed a fairly high incidence of VTE events. As previously discussed [1], events that occurred at home and were diagnosed out of hospital were included in our studies. The incidence rate we observed in western Brittany was indeed higher than the rate found in a US community-based study [3] that used only hospital records, but was consistent, as regards DVT incidence, with a communitybased study performed in Sweden [10].Our data raise questions about prevention in patients with cancer and hospitalized patients [8,9]. Further investigations are warranted to specify whether a preventive therapy was effectively implemented or not. To some extent, it hopefully was and obviously failed, and the next question is why?In conclusion, a straightforwardly recognizable situation, i.e. hospitalization and/or history of cancer, was present in 41.5% of VTE cases. In those situations, optimization of preventive therapies should be a priority.

Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management

“…Patients with congenital dysfibrinogenemia can be identified during the clinical investigation of bleeding or thrombosis , or following miscarriage . However, most individuals are asymptomatic, and are usually discovered by the prolongation of routine parameters of coagulation, such as prothrombin time (PT) and activated partial thromboplastin time (APTT) (Table ).…”

Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemias

“…There are a number of reports in unrelated families of dysfibrinogenaemia due to heterozygosity for BbArg14Cys; a missense mutation affecting the fibrinopeptide B thrombin cleavage site [31,[61][62][63][64][65][66]. These variants typically had mild thrombin and reptilase time prolongation and were associated with a thrombotic tendency, with one published exception, in which the patient was asymptomatic [61].…”

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).…”