Eikelboom J W, Ivey L, Ivey J, Baker R I
McMaster University, HGH-McMaster Clinic, Hamilton, Ontario, Canada.
Blood Coagul Fibrinolysis. 1999 Jan;10(1):1-5.
The 20210A prothrombin mutation has recently been associated with an increased risk of venous thrombosis, but the mechanism of the increased thrombotic risk in affected persons has not been elucidated. We report on a thrombophilic family in which the proband presented with cerebral vein thrombosis and homozygosity for the 20210A prothrombin mutation as her only identifiable risk factor for venous thrombosis. Extended genotyping of family members revealed seven other affected, but asymptomatic, first-degree relatives (one A/A homozygote and six G/A heterozygotes). Plasma levels of prothrombin, prothrombin fragments 1 + 2 and thrombin-antithrombin complexes were highest in A/A homozygotes, intermediate in G/A heterozygotes and lowest in those with the G/G homozygous normal genotype, while D-dimer levels were elevated only in A/A homozygotes. Our results suggest that the 20210A prothrombin mutation is associated with activation of coagulation and increased thrombin generation, not only in patients with a past history of thrombosis but also in otherwise healthy asymptomatic persons. In a similar fashion to the homozygous factor V Leiden mutation, patients with the homozygous 20210A prothrombin mutation could be at highest risk of thrombosis, as suggested by our patient who presented with unusual thrombosis.
20210A凝血酶原突变最近被认为与静脉血栓形成风险增加有关，但尚未阐明受影响个体血栓形成风险增加的机制。我们报告了一个血栓形成倾向家族，先证者出现脑静脉血栓形成，且20210A凝血酶原突变纯合子是其唯一可识别的静脉血栓形成风险因素。对家庭成员进行的扩展基因分型显示，还有其他7名受影响但无症状的一级亲属（1名A/A纯合子和6名G/A杂合子）。A/A纯合子的血浆凝血酶原、凝血酶原片段1+2和凝血酶-抗凝血酶复合物水平最高，G/A杂合子次之，G/G纯合正常基因型者最低，而D-二聚体水平仅在A/A纯合子中升高。我们的结果表明，20210A凝血酶原突变不仅与有血栓形成病史的患者有关，而且与其他健康无症状个体的凝血激活和凝血酶生成增加有关。与纯合因子V莱顿突变类似，如我们这位出现不寻常血栓形成的患者所示，纯合20210A凝血酶原突变患者可能处于最高的血栓形成风险中。
