The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications
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Kovač, MirjanaMitić, Gorana
Miković, Zeljko
Mandić, Vesna
Miljić, Predrag
Mitrović, Mirjana
Tomić, Branko
Bereczky, Zsuzsanna
Article (Published version)
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Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In w...omen with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.
Keywords:
SERPINC1 mutations / Pregnancy outcome / Antithrombin deficiencySource:
Thrombosis Research, 2019, 173, 12-19Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (RS-MESTD-Basic Research (BR or ON)-173008)
- Hungarian Scientific Research Fund [OTKA K116228]
- Ministry of National Economy, Hungary [GINOP-2.3.2-15-2016-00039]
DOI: 10.1016/j.thromres.2018.11.006
ISSN: 0049-3848
PubMed: 30458337
WoS: 000454370700003
Scopus: 2-s2.0-85056672197
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kovač, Mirjana AU - Mitić, Gorana AU - Miković, Zeljko AU - Mandić, Vesna AU - Miljić, Predrag AU - Mitrović, Mirjana AU - Tomić, Branko AU - Bereczky, Zsuzsanna PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1287 AB - Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Thrombosis Research T1 - The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications EP - 19 SP - 12 VL - 173 DO - 10.1016/j.thromres.2018.11.006 ER -
@article{ author = "Kovač, Mirjana and Mitić, Gorana and Miković, Zeljko and Mandić, Vesna and Miljić, Predrag and Mitrović, Mirjana and Tomić, Branko and Bereczky, Zsuzsanna", year = "2019", abstract = "Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Thrombosis Research", title = "The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications", pages = "19-12", volume = "173", doi = "10.1016/j.thromres.2018.11.006" }
Kovač, M., Mitić, G., Miković, Z., Mandić, V., Miljić, P., Mitrović, M., Tomić, B.,& Bereczky, Z.. (2019). The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications. in Thrombosis Research Pergamon-Elsevier Science Ltd, Oxford., 173, 12-19. https://doi.org/10.1016/j.thromres.2018.11.006
Kovač M, Mitić G, Miković Z, Mandić V, Miljić P, Mitrović M, Tomić B, Bereczky Z. The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications. in Thrombosis Research. 2019;173:12-19. doi:10.1016/j.thromres.2018.11.006 .
Kovač, Mirjana, Mitić, Gorana, Miković, Zeljko, Mandić, Vesna, Miljić, Predrag, Mitrović, Mirjana, Tomić, Branko, Bereczky, Zsuzsanna, "The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications" in Thrombosis Research, 173 (2019):12-19, https://doi.org/10.1016/j.thromres.2018.11.006 . .