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|Title: ||Thrombophilia investigations in Malaysian women with recurrent pregnancy loss|
|Authors: ||Thiruchelvam Ayadurai|
Recurrent pregnancy loss
Factor V Leiden
|Issue Date: ||Dec-2008 |
|Publisher: ||University of Malaya|
|Abstract: ||BACKGROUND: The status of thrombophilia in Asian women with recurrent abortions and stillbirths is obscure and poorly understood. Collectively known as recurrent pregnancy loss (RPL), it is now apparent that thrombophilia is responsible for a large number of failed pregnancies. Thrombophilia exerts a thrombotic risk at the placental-microvasculature, compromising the well-being of the developing fetus and culminating in poor pregnancy outcome. The common thrombophilia risk factors are: Factor V Leiden (FVL) and Prothrombin G20210A (PT G20210A) mutations of the haemostasis system, activated protein C resistance (APCR) and protein C and S deficiencies of the protein C pathway, autoimmune antibodies of antiphospholipids and lupus anticoagulant, and Methylene Tetrahydrofolate Reductase (MTHFR C677T) mutation of the homocysteine metabolic pathway. The two most common thrombophilia markers, FVL and PT G20210A, have been identified in Caucasian subjects with a prevalence of between 8.0% to 48.0% and 1.0% to 8.0%, respectively. However, numerous studies have documented the non-existence or extreme rarity of these two important thrombophilia markers in patients with Asian ancestries - hence, the basis for the overwhelming assumption among the local clinicians that thrombophilia is rare among Asians and therefore, laboratory investigations are irrelevant. Consequently, the diagnosis of thrombophilia-induced RPL and its management with antithrombotic therapy in Malaysian women with unexplained RPL is rare in clinical-practice. The Maternity Hospital in Kuala Lumpur registered a high prevalence of unexplained pregnancy losses among young “healthy” Malaysian women. These subjects were free from all known pathologies, except for thrombophilia, which was never investigated. This study attempts to test the hypothesis that a significant number of Malaysian women with RPL, like their Caucasian counterparts, have thrombophilia abnormalities. In doing so, the study would also be determining the relationship between thrombophilia and unexplained RPL, in otherwise healthy Malaysian women (RPL-subjects).
METHOD: 402 RPL-subjects and 160 healthy parous-controls from three main ethnic groups of the Malaysian population (Malays, Chinese and Indians) were investigated for thrombophilia. FVL, PT G20210A and MTHFR C677T were identified by polymerase chain reactions. APCR, protein C (PC), protein S (PS), antithrombin (AT) and antiphospholipid (aPL) antibodies were identified using clot-based, chromogenic and enzyme-linked immunosorbent assays.
RESULTS: Thrombophilia was identified in 27.4% (110/402; p<0.001) of the RPL-subjects, compared to 1.25% (2/160) in the parous-controls. APCR occurred in 21.6% (87/402; p<0.001) of the RPL-subjects. The abnormalities in the PC pathway was caused by FVL (9.2%=8/87), PS deficiency (51.7%=45/87), PC deficiency (6.9%=6/87), combined PS and PC deficiencies (6.9%=6/87) and unidentifiable “Non-specific” abnormalities (25.3%=22/87). FVL (2% vs 0%) and PT G20210A (0.5% vs 0%) were identified in the Malay and Indian ethnic RPL-subjects. The Chinese ethnic group was free from the FVL and PT G20210A mutations. MTHFR C677T occurred with a higher prevalence in the RPL-subjects compared to the parous-controls (35.3% vs 23.1%; p=0.002). Antiphospholipid antibodies were detected in 5.0% (p=0.019) of the RPL-subjects, however only one RPL-subject had AT deficiency (0.25%).
CONCLUSION: Thrombophilia was identified in more than one-quarter (27.4%) of the so-called “healthy” Malaysian women with unexplained RPL, thereby confirming the hypothesis that thrombophilia is indeed a significant abnormality in the RPL-subjects. APCR was the most common thrombophilia marker - being identified in more than one-fifth (21.6%) of the RPL-subjects investigated. Acquired APCR was more prevalent in the Asians, whereas in the Caucasians it was the Inherited form. FVL and PT G20210A were identified in the Malay and Indian ethnic groups, disputing all previous studies on the non-occurrence of both these mutations in patients with Asian ancestries. Thrombophilia is an important pathology to be reckoned with and should no longer be considered a rare disorder among Malaysian women with RPL. In light of the present evidence, local clinicians should now re-consider thrombophilia investigations for Malaysian women with unexplained RPL, with the option of extending this investigation to other thromboembolic disorders in Malaysian patients.|
|Description: ||Thesis (PhD) -- Faculty of Medicine, Universiti Malaya, 2008.|
|Appears in Collections:||PhD Theses: Medicine|