Girolami A, Scarano L, Saggiorato G, Girolami B, Bertomoro A, Marchiori A
University of Padua Medical School, Institute of Medical Semeiotics, Italy.
Blood Coagul Fibrinolysis. 1998 Oct;9(7):557-69. doi: 10.1097/00001721-199810000-00001.
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.
1947年，奎克等人首次描述了凝血酶原（因子II）缺乏症，不过1969年夏皮罗等人首次报告了凝血酶原异常情况。这种病症至今仍被认为非常罕见。尽管罕见，但该缺陷使我们对先天性和获得性凝血酶原缺乏症的认识有了重要进展。凝血酶原缺乏或异常的诊断可通过凝血、发色底物和免疫测定相结合的方法进行。在真正缺乏的情况下，无论激活剂如何，所有这些测定都会出现平行下降。如果在凝血测定中发现差异，特别是使用蝰蛇毒时，应怀疑存在异常凝血酶原血症。通常，纯合子的活性水平低于正常水平的10%，杂合子则在40%至60%之间。先天性异常凝血酶原血症中的因子II水平变化更大，因为可能会遇到杂合子异常与杂合子“真正”缺乏之间或两种不同异常之间的纯合子、杂合子和复合杂合子。通常，因子II水平在正常水平的1%至50%之间。先天性异常凝血酶原血症中的抗原水平将正常、接近正常或略有下降，但总是高于相应的凝血水平。凝血酶原活性和抗原平行下降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号染色体上。它由10个外显子和8个内含子组成。分子生物学研究在一些异常凝血酶原血症中发现了几个点突变。纯合子“真正”缺乏时出血表现可能很严重，异常凝血酶原血症中的出血表现可能变化更大。杂合子通常无症状。预后各不相同，一般与凝血酶原活性水平一致。在纯合子真正缺乏的情况下，曾有过关节积血和颅内出血的描述。替代疗法基于给予凝血酶原复合物浓缩物或血浆。注射的凝血酶原半衰期较长，约70小时，因此不难达到止血有效水平（约为正常水平的50%）。
