Risk of bleeding and thrombosis in inherited qualitative fibrinogen disorders
Risk of bleeding and thrombosis in inherited qualitative fibrinogen disorders
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DOI：
10.1111/ejh.13296
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发表时间：
2019-08-01
影响因子：
3.1
通讯作者：
Radossi, Paolo
中科院分区：
文献类型：
--
作者：
Castaman, Giancarlo;Giacomelli, Sofia H.;Radossi, Paolo
目的：遗传性异常纤维蛋白原血症是一种罕见的疾病，其出血或血栓形成的风险以及致病突变类型的临床研究很少。材料与方法对来自19个非血缘家系的50例遗传性异常纤维蛋白原血症患者的实验室、临床和基因型特征进行分析。结果所有指标病例的Clauss法纤维蛋白原活性均低于正常值，而PT衍生法纤维蛋白原活性低于正常值的仅占57.9%。在三个家族中，低异常纤维蛋白原血症是明显的，与三个新的突变（FGB中的Ter 492 Gln，Cys 365 Asp和FGG中的Leu 370 Phe）相关。还鉴定了另外三种新突变（FGA中的Arg 114 Lys，FGG中的Ile 131 Thr和Trp 234 Arg）。在30%的患者中，通过ISTH-BAT评估的出血症状评分至少为1分，显著出血症状主要存在于女性患者中，尤其是与妊娠相关的患者。2例FGB Arg 44 Cys患者发生静脉血栓栓塞，2例FGA Arg 35 His患者在老年时发生缺血性卒中。结论本研究证实了遗传性异常纤维蛋白原血症的临床特征的异质性，由于广泛的致病突变。需要更大规模的多中心研究来评估某些突变与出血或血栓形成的明确相关性。
Objectives Inherited dysfibrinogenemia is a rare disorder, for which clinical studies related to the risk of bleeding or thrombosis and the type of causative mutation are scanty. Materials and Methods We analyzed the laboratory, clinical, and genotypic features of 50 patients with inherited dysfibrinogenemia belonging to 19 unrelated families. Results In all the index cases, fibrinogen activity by Clauss method was below the normal range, while it was observed in 57.9% only by PT-derived method. In three families, hypodysfibrinogenemia was evident, associated with three novel mutations (Ter492Gln in FGB, Cys365Asp, and Leu370Phe in FGG). Three additional novel mutations were also identified (Arg114Lys in FGA, Ile131Thr and Trp234Arg in FGG). Bleeding symptoms assessed by ISTH-BAT scored at least 1 in 30% of patients and, significant bleeding symptoms were mainly present in female patients, especially associated with pregnancy. Two patients with FGB Arg44Cys suffered from venous thromboembolism, and two with FGA Arg35His had ischemic stroke at older age. Conclusions This study confirms the heterogeneity of clinical features in inherited dysfibrinogenemia, due to the wide spectrum of the causative mutations. Larger multicenter studies are needed to assess the definitive correlation of some mutations with bleeding or thrombosis.