Congenital deficiencies and abnormalities of prothrombin.
Congenital deficiencies and abnormalities of prothrombin.
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先天性凝血酶原缺陷和异常。
DOI：
10.1097/00001721-199810000-00001
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发表时间：
1998
影响因子：
1.1
通讯作者：
A. Marchiori
中科院分区：
文献类型：
--
作者：
A. Girolami;L. Scarano;G. Saggiorato;B. Girolami;A. Bertomoro;A. Marchiori
Quick 等人于 1947 年首次描述了凝血酶原（II 因子）缺乏症，尽管 Shapiro 等人于 1969 年报道了第一个凝血酶原异常。这种情况仍然被认为非常罕见。尽管这种缺陷很罕见，但它使我们对先天性和后天性凝血酶原缺陷的理解有了重大进展。凝血酶原缺乏或异常的诊断可以结合凝血、显色和免疫学测定来进行。在真正缺乏的情况下，无论激活剂如何，所有这些测定都观察到平行下降。如果发现凝血试验之间存在差异，特别是使用毒蛇毒液，则应怀疑凝血酶原血症。通常，纯合子的活性水平低于正常值的 10%，杂合子的活性水平则在 40% 到 60% 之间。先天性凝血酶原异常血症中的因子 II 水平变化较大，因为可能会遇到纯合子、杂合子以及杂合子异常和杂合子“真正”缺陷之间或两种不同异常之间的复合杂合子。通常，因子 II 的水平在正常值的 1% 到 50% 之间变化。先天性凝血酶原异常血症的抗原水平将是正常、接近正常或略有下降，但始终高于凝血对应物。凝血酶原活性和抗原同时降低的病例不应被视为低凝血酶原血症的例子。参与凝血酶原合成的基因位于11号染色体，由10个外显子和8个内含子组成。分子生物学研究发现一些凝血酶原血症存在几个点突变。纯合子“真”缺陷的出血表现可能很严重，而凝血酶原血症的出血表现可能更加多变。杂合子通常无症状。预后各不相同，通常与凝血酶原活性水平一致。在纯合性真缺陷中，已描述了关节积血和颅内出血。替代疗法基于给予凝血酶原复合物浓缩物或血浆。注射的凝血酶原的半衰期较长（约 70 小时），可以毫无困难地达到止血有效水平（约正常水平的 50%）。
Prothrombin (factor II) deficiency was first described in 1947 by Quick et al., although the first prothrombin abnormality was reported in 1969 by Shapiro et al. The condition is still considered very rare. In spite of its rarity, the defect has allowed important improvements in our understanding of both congenital and acquired prothrombin deficiencies. The diagnosis of prothrombin deficiency or abnormality can be made using a combination of clotting, chromogenic and immunological assays. In cases of true deficiency, a parallel decrease in all these assays is observed, regardless of the activating agent. If discrepancies among the clotting assays are noted, particularly using viper venoms, a dysprothrombinemia should be suspected. Usually, activity levels less than 10% of normal are found in homozygotes, and between 40 and 60% in heterozygotes. Factor II levels in congenital dysprothrombinemias are more variable since one may encounter homozygotes, heterozygotes and compound heterozygotes between a heterozygous abnormality and heterozygous 'true' deficiency or between two distinct abnormalities. Usually the levels of factor II vary between 1 and 50% of normal. Antigen levels in congenital dysprothrombinemias will be normal, near normal or slightly decreased but always higher than the clotting counterpart. Cases with a parallel decrease in prothrombin activity and antigen should not be considered as examples of hypoprothrombinemia. The gene involved in the synthesis of prothrombin is located in chromosome 11. It is composed of 10 exons and 8 introns. Molecular biology studies have discovered several point mutations in some of the dysprothrombinemias. Bleeding manifestations may be severe in homozygous 'true' deficiency and may be more variable in dysprothrombinemias. Heterozygotes are usually asymptomatic. Prognosis is variable and generally in agreement with the prothrombin activity level. In homozygous true deficiency, hemarthroses and intracranial bleeding have been described. Substitution therapy is based on the administration of prothrombin complex concentrates or of plasma. The long half-life of prothrombin injected, about 70 h, allows the achievement of hemostatically effective levels (about 50% of normal) without difficulty.