Thrombophilia investigation in Malaysian women with recurrent pregnancy loss

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.