Girolami Antonio, Cosi Elisabetta, Sambado Luisa, Girolami Bruno, Randi Maria Luigia
Department of Medicine, University of Padua Medical School, Padua, Italy.
Division of Medicine, Padua City Hospital, Padua, Italy.
Semin Thromb Hemost. 2015 Jun;41(4):359-65. doi: 10.1055/s-0034-1544000. Epub 2015 Apr 14.
Factor X (FX) plays a pivotal role in blood coagulation. FX represents the point where all coagulation systems converge and, once activated, it converts prothrombin into thrombin. The discovery and definition of FX are based on the description between 1956 and 1957 about three patients and their families with a peculiar defect later demonstrated to be almost identical. These patients were an American (Mr. Stuart), a British (Ms. Prower), and a Swiss with Italian background (infant Delia B). We stated "almost identical" because immunological and molecular biology studies subsequently revealed that even though the basic clotting defect was identical, the FX protein level and the mutation were different in each case. Mr. Stuart had no FX protein in his plasma and the mutation was Val298Met (homozygote). Ms. Prower instead had a normal level of FX protein and the mutation was Arg287Trp + Asp282Asn (compound heterozygote). Unfortunately, the status of the Swiss patient in this regard is not known. Subsequent studies described a few major variants (FX Friuli, FX Melbourne, FX Padua, and other similar patients), which showed peculiar activation patterns (FX Friuli had a normal Russell viper venom clotting time; FX Melbourne was defective only in the intrinsic coagulation system; FX Padua, on the contrary, was defective only in the extrinsic coagulation system). All these studies have informed on the great heterogeneity and complexity of the FX defect. The story of the discovery and classification of FX deficiency has contributed considerably to our understanding of blood coagulation. The three original families and the families of the major variants, together with the researchers that discovered them, should be remembered with deep respect and gratitude.
凝血因子X（FX）在血液凝固过程中起着关键作用。FX代表所有凝血系统汇聚的节点，一旦被激活，它会将凝血酶原转化为凝血酶。FX的发现和定义基于1956年至1957年间对三名患者及其家族的描述，后来证明他们存在一种几乎相同的特殊缺陷。这些患者分别是一名美国人（斯图尔特先生）、一名英国人（普罗尔女士）和一名有意大利背景的瑞士人（婴儿迪莉娅·B）。我们说“几乎相同”是因为随后的免疫学和分子生物学研究表明，尽管基本的凝血缺陷相同，但每种情况下FX蛋白水平和突变是不同的。斯图尔特先生血浆中没有FX蛋白，突变为Val298Met（纯合子）。相反，普罗尔女士的FX蛋白水平正常，突变为Arg287Trp + Asp282Asn（复合杂合子）。不幸的是，这位瑞士患者在这方面的情况尚不清楚。随后的研究描述了一些主要变体（弗留利FX、墨尔本FX、帕多瓦FX及其他类似患者），它们表现出特殊的激活模式（弗留利FX的罗素蝰蛇毒凝血时间正常；墨尔本FX仅在内源性凝血系统中存在缺陷；相反，帕多瓦FX仅在外源性凝血系统中存在缺陷）。所有这些研究都揭示了FX缺陷的高度异质性和复杂性。FX缺乏症的发现和分类历程对我们理解血液凝固有很大贡献。应该怀着深深的敬意和感激铭记最初的三个家族以及主要变体的家族，还有发现它们的研究人员。
