Clinical features and molecular basis of 102 Chinese patients with congenital dysfibrinogenemia

Introduction: Congenital dysfibrinogenemia (CD) is a rare qualitative disorder of fibrinogen (Fg) with heterogeneous clinical manifestations. We aimed to analyze clinical phenotype and molecular basis of 102 Chinese CD patients and to evaluate the application of thromboelastography (TEG). Materials and methods: Clinical manifestations were recorded and quantified using the consensus ISTH bleeding assessment tool. Kaolin activated TEG and functional Fg TEG were applied in 30 patients. Genetic analysis of Fg genes were performed by direct sequencing. Results: 27.5% patients experienced bleeding, 3.9% had thrombosis and 68.6% were asymptomatic. Females were more prone to experience bleeding (P = 0.01). Significant difference (P < 0.05) in TEG results were found between patients with hot-spot mutations at A alpha Arg35(16) and gamma Arg301(275), but were not identified between patients with and without bleeding. Normal TEG results were found in patients with mutations at AaArg35(16), A alpha Pro37(18) or A alpha Arg38(19). Six novel mutations were identified, including A alpha Gly33(14)del, A alpha Asp57(38)_Trp60(41)delIVS2 + 1_ + 2GTdel, A alpha Phe742(723)Tyr, gamma Asn334(308)Thr, gamma Gly335(309)Cys and gamma Trp395(369)Leu. Conclusions: CD patients have similar clinical manifestations and hot-spot mutations worldwide with no ethnic difference. TEG results could not indicate the bleeding risk in patients, but priority of mutation screening at thrombin cleavage site or polymerization site on Aa chain may be given if TEG results are normal. (C) 2015 Elsevier Inc. All rights reserved.