Rare inherited disorders of fibrinogen
Rare inherited disorders of fibrinogen
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DOI：
10.1111/j.1365-2516.2008.01831.x
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发表时间：
2008-11-01
期刊：
影响因子：
3.9
通讯作者：
Dimichele, D. M.
中科院分区：
文献类型：
--
作者：
Acharya, S. S.;Dimichele, D. M.
纤维蛋白原是一种由三个基因（FGA、FGB、FGG）编码的六聚体糖蛋白，聚集在染色体 4q 上，作为形成止血塞所需的纤维蛋白单体的前体，参与凝血的最后步骤。纤维蛋白原异常的遗传性疾病非常罕见，并且其临床特征不如其他一些遗传性出血性疾病。为了描述这些罕见疾病的临床表现、分子缺陷和治疗方式，Medline 从 1966 年 1 月到 2007 年 9 月对大型研究和登记中报告的这些疾病进行了搜索。遗传性纤维蛋白原疾病可表现为数量缺陷（纤维蛋白原血症和低纤维蛋白原血症）或质量缺陷（纤维蛋白原异常血症）。定量纤维蛋白原缺乏可能是由于影响纤维蛋白原合成或加工的突变引起的，而定性缺陷是由导致纤溶系统异常聚合、有缺陷的交联或有缺陷的组装的突变引起的。临床表现多种多样，从无症状到发生灾难性危及生命的出血或血栓栓塞事件。出血处理包括使用纯化的血浆浓缩物、冷沉淀或新鲜冷冻血浆。使用其中一些产品会带来病毒传播、抗体产生和血栓栓塞事件的风险。在伊朗、意大利和北美建立的登记处通过探索分子缺陷促进了对这些疾病的更好了解。通过美国和国际努力建立的罕见出血性疾病登记处有望鼓励更安全、有效的产品的开发和许可。
Fibrinogen, a hexameric glycoprotein encoded by three genes - FGA, FGB, FGG - clustered on chromosome 4q is involved in the final steps of coagulation as a precursor of fibrin monomers required for the formation of the haemostatic plug. Inherited disorders of fibrinogen abnormalities are rare and not as well clinically characterized as some other inherited bleeding disorders. To characterize the clinical manifestations, molecular defects and treatment modalities of these rare disorders, a Medline search from January 1966 to September 2007 for these disorders reported in large studies and registries was undertaken. Inherited fibrinogen disorders can manifest as quantitative defects (afibrinogenemia and hypofibrinogenemia) or qualitative defects (dysfibrinogenemia). Quantitative fibrinogen deficiencies may result from mutations affecting fibrinogen synthesis, or processing while qualitative defects are caused by mutations causing abnormal polymerization, defective cross-linking or defective assembly of the fibrinolytic system. Clinical manifestations vary from being asymptomatic to developing catastrophic life-threatening bleeds or thromboembolic events. Management of bleeds includes use of purified plasma-derived concentrates, cryoprecipitate or fresh frozen plasma. Use of some of these products carries risks of viral transmission, antibody development and thromboembolic events. Establishment of registries in Iran, Italy and North America has fostered a better understanding of these disorders with an attempt to explore molecular defects. Rare Bleeding Disorder Registries developed through the United States and international efforts hopefully will encourage development and licensure of safer, effective products.