Girolami Antonio, Ferrari Silvia, Cosi Elisabetta, Girolami Bruno, Lombardi Anna Maria
a Department of Medicine , University of Padua Medical School , Padua , Italy.
b Division of Medicine , Padua City Hospital , Padua , Italy.
Hematology. 2018 Mar;23(2):105-110. doi: 10.1080/10245332.2017.1359900. Epub 2017 Aug 1.
Congenital prothrombin deficiency is one of the rarest clotting disorders. It is commonly subdivided in Type I defects or cases of 'true' prothrombin deficiency characterized by a concomitant decrease in FII activity and antigen and in Type II or dysprothrombinemias, in which FII activity is low but FII antigen is normal or near normal. A bleeding tendency, often a severe one, is the hallmark of the two-defects even though the bleeding is usually less severe in the Type 2 defects or dysprothrombinemias.
An extensive search of published cases of prothrombin deficiency was carried out in Pubmed and Scopus. The search started in 2012, after the publication of the first family with dysprothrombinemia and venous thrombosis. A few additional families were found.
Recent studies have demonstrated that the Type 2 defects are heterogeneous. Several heterozygous mutations involving the Arg596 residue of exon 14 have been demonstrated not be associated with a bleeding tendency but, surprisingly, with venous thromboses. Mutations in close areas of prothrombin have failed to show the same pattern.
These observations have required a reclassification of prothrombin defects. To the Type I and Type II defects, a Type III has to be added characterized by the absence of bleeding and the presence of venous thrombosis. It is not clear yet if this special variant of Type II defect is limited to the Arg596 mutations or if other residues may be involved.
先天性凝血酶原缺乏症是最罕见的凝血障碍之一。它通常分为I型缺陷或“真正的”凝血酶原缺乏症，其特征是FII活性和抗原同时降低；以及II型或异常凝血酶原血症，其中FII活性低但FII抗原正常或接近正常。出血倾向，通常较为严重，是这两种缺陷的标志，尽管在II型缺陷或异常凝血酶原血症中出血通常不太严重。
在PubMed和Scopus上对已发表的凝血酶原缺乏症病例进行了广泛检索。检索始于2012年，即首个患有异常凝血酶原血症和静脉血栓形成的家族发表之后。又发现了一些其他家族。
最近的研究表明，II型缺陷是异质性的。已证实涉及外显子14的Arg596残基的几种杂合突变与出血倾向无关，但令人惊讶的是，与静脉血栓形成有关。凝血酶原附近区域的突变未显示出相同的模式。
这些观察结果需要对凝血酶原缺陷进行重新分类。在I型和II型缺陷之外，必须增加III型，其特征是无出血但有静脉血栓形成。尚不清楚这种特殊的II型缺陷变体是否仅限于Arg596突变，或者是否可能涉及其他残基。
