Di Micco Pierpaolo, D'Uva Maristella, Strina Ida, Mollo Antonio, Amato Valeria, Niglio Alferio, De Placido Giuseppe
IV Divisione di Medicina Interna e Patologie Epato-Bilio-Metaboliche, Seconda Università di Napoli, Naples, Italy.
J Transl Med. 2004 Nov 9;2(1):38. doi: 10.1186/1479-5876-2-38.
D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis, so increased d-dimer is detectable in patients affected by thrombosis. Yet, several studies showed that also infertility, in particular secondary infertility due to recurrent fetal losses, has been often related to thrombotic events, in particular in women carrying thrombotic risk factors such as inherited thrombophilia (MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms and/or inhAfter this screening we selected 39erited protein C, protein S, AT III deficiency) or acquired thrombophilia (primary antiphospholipid syndrome, acquired protein C, protein S, AT III deficiency, drugs induced thrombophilia). However, because its high predictive negative value in case of suspected thrombosis, increased d-dimer has been often associated to subclinical thrombophilia. The aim of this study is to investigate the role of d-dimer as first marker of thrombophilia in women affected by unexplained infertility and subsequently to search the cause of increased d-dimer, such as inherited and/or acquired thrombophilia. PATIENTS AND METHODS: We selected 79 patients with unexplained primary or secondary infertility. We excluded 40 patients affected by hydrosalpinx, uterine fibroids, uterine malformations, endocrinological and immunological diseases, luteal insufficiency, cytogenetical alterations. All remaining 39 patients were tested for d-dimer and divided in two groups: the patients of group A (25 patients) showed increased plasma d-dimer, in group B were included 14 patients with normal plasma level of d-dimer. After this step all 39 patients were screened for MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms, protein C, protein S, AT III, anticardiolipin IgM and IgG, lupus anticoagulant. In the control group were included 15 age matched women without sterility problems referred to our outpatient's section of vascular medicine for suspected deep venous thrombosis.Statistical analysis was based on chi2 test, differences were considered to be significant if p < 0.05. RESULTS: D-dimer was increased in 25/39 and 20/25 showed inherited/acquired thrombophilia while patients with normal d-dimer showed inherited/acquired thrombophilia in 7/14 (p: < 0.05, s). DISCUSSION: D-dimer is a well known marker of hypercoagulable state, in particular its high predictive negative value in case of suspected thrombosis has been recognised by several reports. Yet, increased d-dimer has been identified also for subclinical thrombophilia besides for vascular thrombosis. Our data, in fact, for the first time suggest an interesting role of d-dimer to identify women affected by unexplained primary or secondary infertility and thrombophilia. So, probably there is a role for d-dimer in these subjects for its predictive positive value. Of course, further data on large based population are needed to confirm our results, because these findings may speed up a diagnostic screening in these patients also for a good cost/effectiveness of this test.
D - 二聚体被认为是高凝状态和内源性纤维蛋白溶解的标志物，因此在血栓形成患者中可检测到D - 二聚体升高。然而，多项研究表明，不孕症，尤其是因反复流产导致的继发性不孕症，也常与血栓形成事件相关，特别是在携带血栓形成风险因素的女性中，如遗传性易栓症（MTHFRC677T、PTHRA20210G、凝血因子V莱顿多态性和/或遗传性蛋白C、蛋白S、抗凝血酶III缺乏）或获得性易栓症（原发性抗磷脂综合征、获得性蛋白C、蛋白S、抗凝血酶III缺乏、药物诱导的易栓症）。然而，由于其在疑似血栓形成时具有较高的预测阴性价值，D - 二聚体升高常与亚临床易栓症相关。本研究的目的是调查D - 二聚体作为不明原因不孕症女性易栓症的首个标志物的作用，并随后寻找D - 二聚体升高的原因，如遗传性和/或获得性易栓症。
我们选择了79例不明原因的原发性或继发性不孕症患者。我们排除了40例受输卵管积水、子宫肌瘤、子宫畸形、内分泌和免疫疾病、黄体功能不全、细胞遗传学改变影响的患者。其余39例患者均检测了D - 二聚体，并分为两组：A组（25例患者）血浆D - 二聚体升高，B组包括14例血浆D - 二聚体水平正常的患者。在此步骤之后，对所有39例患者进行了MTHFRC677T、PTHRA20210G、凝血因子V莱顿多态性、蛋白C、蛋白S、抗凝血酶III、抗心磷脂IgM和IgG、狼疮抗凝物的筛查。对照组包括15例年龄匹配、无不孕问题的女性，她们因疑似深静脉血栓而转诊至我们血管医学门诊。统计分析基于卡方检验，如果p < 0.05，则认为差异具有统计学意义。
39例患者中有25例D - 二聚体升高，其中20/25例显示遗传性/获得性易栓症，而D - 二聚体正常的患者中有7/14例显示遗传性/获得性易栓症（p：< 0.05，s）。
D - 二聚体是众所周知的高凝状态标志物，特别是其在疑似血栓形成时的高预测阴性价值已被多篇报道所认可。然而，除了血管血栓形成外，D - 二聚体升高也已在亚临床易栓症中被发现。事实上，我们的数据首次表明D - 二聚体在识别不明原因的原发性或继发性不孕症及易栓症女性中具有有趣的作用。因此，D - 二聚体在这些受试者中可能因其预测阳性价值而发挥作用。当然，需要更多基于大样本量人群的数据来证实我们的结果，因为这些发现可能会加快对这些患者的诊断筛查，同时该检测具有良好的成本效益。
