马来西亚复发性流产女性的血栓形成倾向调查。

Thrombophilia investigation in Malaysian women with recurrent pregnancy loss.

作者信息

Ayadurai Thiruchelvam, Muniandy Sekaran, Omar Siti Zawiah

机构信息

Department of Molecular Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.

出版信息

J Obstet Gynaecol Res. 2009 Dec;35(6):1061-8. doi: 10.1111/j.1447-0756.2009.01067.x.

DOI:10.1111/j.1447-0756.2009.01067.x

PMID:20144172

Abstract

AIM

The status of thrombophilia in Asian women with recurrent pregnancy loss (RPL) is obscure and poorly understood. Numerous studies suggest the non-existence or extreme rarity of the two important thrombophilia markers, factor V Leiden (FVL) and prothrombin G20210A (PTG) mutations, in patients of Asian ancestries. Thus, the consensus that thrombophilia is rare among Asians and laboratory investigations is irrelevant. We therefore investigated Malaysian women with RPL for thrombophilia abnormalities.

METHODS

A total of 402 patients (RPL subjects) and 160 female controls were screened for FVL, PTG and methylene tetrahydrofolate reductase mutations using polymerase chain reaction, activated protein C resistance (APC-R) using clot-based tests, protein C and antithrombin using chromogenic tests, and protein S and antiphospholipid antibodies using enzyme-linked immunosorbent assays.

RESULTS

APC-R was identified in 21.6% (87/402) of the RPL subjects. Of the 87 APC-R positive RPL subjects, 9.2% (8/87) were due to FVL, 51.7% (45/87) had protein S deficiency, 6.9% (6/87) had protein C deficiency, 6.9% (6/87) had combined protein S and protein C deficiencies, 1.1% (1/87) had antithrombin deficiency and 25.3% (22/87) had unidentifiable non-specific abnormalities. Antiphospholipid antibodies were identified in 4.2% (17/402) of the RPL subjects. FVL (2% = 8/402) and PTG (0.5% = 2/402) were identified in the Malay and Indian RPL subjects, but there were none in the Chinese subjects or the controls. Methylene tetrahydrofolate reductase was identified in 35.3% (142/402) of the RPL subjects.

CONCLUSIONS

Thrombophilia was identified in more than one-quarter (26.6% = 107/402) of the RPL subjects. APC-R not caused by FVL mutation was the most common thrombophilia marker in Malaysians, whereas in Caucasians it was the APC-R due to FVL mutation. The identification of FVL and PTG mutations in Malaysian women with RPL disputes prevailing evidences suggesting its non-occurrence in patients with Asian ancestries.

摘要

目的

亚洲复发性流产（RPL）女性的血栓形成倾向状况尚不明确，了解甚少。众多研究表明，在亚洲裔患者中，两种重要的血栓形成倾向标志物，即凝血因子V莱顿（FVL）和凝血酶原G20210A（PTG）突变不存在或极为罕见。因此，人们形成了血栓形成倾向在亚洲人中罕见且实验室检查无关紧要的共识。我们因此对马来西亚RPL女性进行了血栓形成倾向异常情况的调查。

方法

使用聚合酶链反应对总共402例患者（RPL受试者）和160名女性对照进行FVL、PTG和亚甲基四氢叶酸还原酶突变筛查，使用基于凝血块的检测方法检测活化蛋白C抵抗（APC-R），使用发色底物法检测蛋白C和抗凝血酶，使用酶联免疫吸附测定法检测蛋白S和抗磷脂抗体。

结果

在RPL受试者中，21.6%（87/402）检测出APC-R。在87例APC-R阳性的RPL受试者中，9.2%（8/87）是由于FVL，51.7%（45/87）存在蛋白S缺乏，6.9%（6/87）存在蛋白C缺乏，6.9%（6/87）同时存在蛋白S和蛋白C缺乏，1.1%（1/87）存在抗凝血酶缺乏，25.3%（22/87）存在无法识别的非特异性异常。在RPL受试者中检出抗磷脂抗体的比例为4.2%（17/402）。在马来族和印度族RPL受试者中检测到FVL（2% = 8/402）和PTG（0.5% = 2/402），但华裔受试者和对照中均未检测到。在RPL受试者中，35.3%（142/402）检测出亚甲基四氢叶酸还原酶。

结论

超过四分之一（26.6% = 107/402）的RPL受试者存在血栓形成倾向。在马来西亚人中，非FVL突变导致的APC-R是最常见的血栓形成倾向标志物，而在白种人中，最常见的是由FVL突变导致的APC-R。在马来西亚RPL女性中检测到FVL和PTG突变，这与普遍认为亚洲裔患者不会出现此类突变的证据相矛盾。