Girolami Antonio, Cosi Elisabetta, Ferrari Silvia, Girolami Bruno
1 Department of Medicine, University of Padua Medical School, Padua, Italy.
2 Division of Medicine, Padua City Hospital, Padua, Italy.
Clin Appl Thromb Hemost. 2018 Sep;24(6):845-849. doi: 10.1177/1076029618770741. Epub 2018 Apr 24.
Clotting factor defects are usually associated with bleeding. About 2 decades ago, 2 polymorphisms, one of FII (G20210A) and another of FV (Arg506Gln), have been shown to be associated with prothrombotic state and venous thrombosis. As a consequence, FII and FV could be considered both as prohemorrhagic factors and prothrombotic conditions. Recently, it has been shown that missense mutations in the prothrombin gene of amino acid Arg596 of exon 14 to Leu596, Gln596, or Trp596 caused the appearance of a thrombophilic state and venous thrombosis. These mutated FII are not associated with bleeding, but only with venous thrombosis. Furthermore, they are all heterozygotes for the mutations. No missense mutation associated with thrombosis has been discovered so far for FV. As a consequence, the prothrombotic activity of FII is the result of a polymorphism and of a missense mutation, whereas that of FV derives only from a polymorphism. The observation that a clotting factor defect may be associated with both bleeding or venous thrombosis depending on the site of the mutation has caused an extensive reevaluation of the blood clotting mechanism.
凝血因子缺陷通常与出血有关。大约20年前，已证明两种多态性，一种是凝血因子II（FII，G20210A）的多态性，另一种是凝血因子V（FV，Arg506Gln）的多态性，与血栓前状态和静脉血栓形成有关。因此，FII和FV既可以被视为促出血因素，也可以被视为血栓前状态。最近，已证明凝血酶原基因第14外显子的氨基酸Arg596错义突变为Leu596、Gln596或Trp596会导致血栓形成倾向状态和静脉血栓形成。这些突变的FII与出血无关，仅与静脉血栓形成有关。此外，它们都是突变的杂合子。迄今为止，尚未发现FV有与血栓形成相关的错义突变。因此，FII的血栓前活性是多态性和错义突变的结果，而FV的血栓前活性仅源于多态性。凝血因子缺陷可能根据突变位点与出血或静脉血栓形成相关这一观察结果，引发了对血液凝固机制的广泛重新评估。
