Jingyi Zhou1, Qiulan Ding2, Yaopeng Chen3, Qi Ouyang1, Linlin Jiang1, Jing Dai2, Yeling Lu2, Xi Wu2, Qian Liang2, Hongli Wang1, Xuefeng Wang4. 1. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China. 2. Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China. 3. Department of Laboratory Medicine, The 303 Hospital of Chinese People's Liberation Army, China. 4. Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China. Electronic address: wangxuefeng6336@hotmail.com.
Abstract
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 AαArg35(16) and γArg301(275), but were not identified between patients with and without bleeding. Normal TEG results were found in patients with mutations at AαArg35(16), AαPro37(18) or AαArg38(19). Six novel mutations were identified, including AαGly33(14)del, AαAsp57(38)_Trp60(41)delIVS2+1_+2GTdel, AαPhe742(723)Tyr, γAsn334(308)Thr, γGly335(309)Cys and γTrp395(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 Aа chain may be given if TEG results are normal.
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 CDpatients 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 AαArg35(16) and γArg301(275), but were not identified between patients with and without bleeding. Normal TEG results were found in patients with mutations at AαArg35(16), AαPro37(18) or AαArg38(19). Six novel mutations were identified, including AαGly33(14)del, AαAsp57(38)_Trp60(41)delIVS2+1_+2GTdel, AαPhe742(723)Tyr, γAsn334(308)Thr, γGly335(309)Cys and γTrp395(369)Leu. CONCLUSIONS:CDpatients 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 Aа chain may be given if TEG results are normal.
Authors: Cristina Freire; Richard J Fish; Rui Vilar; Corinne Di Sanza; Steven J Grzegorski; Catherine E Richter; Jordan A Shavit; Marguerite Neerman-Arbez Journal: Blood Adv Date: 2020-11-10
Authors: Eliška Ceznerová; Jiřina Kaufmanová; Žofie Sovová; Jana Štikarová; Jan Loužil; Roman Kotlín; Jiří Suttnar Journal: Int J Mol Sci Date: 2022-01-10 Impact factor: 5.923