Prevalence of Factor V Leiden G1691A and Prothrombin G20210A Gene Mutation Among Pregnant Women: Experience from a Multi-Center Study in Nigeria

Цель исследования: изучить связь феномена резистентности фактора Vа к активированному протеину С (АПС-резистентность) при носительстве мутации гена FVL (1691) GA с клинической реализацией во время беременности тромботических событий и гестационных осложнений, таких как преэклампсия, задержка развития плода и невынашивание беременности. Материалы и методы. Проведено проспективное клиническое когортное исследование 1100 беременных. Выделено 2 когорты: основная группа – 500 пациенток с генотипом FVL (1691) GA и группа контроля – 600 женщин с генотипом FVL (1691) GG. Результаты. Медиана нормализованного отношения (НО) АПС-резистентности в контрольной группе у беременных с генотипом FVL (1691) GG колебалась в диапазоне 1,0→0,86. У беременных – носителей генотипа FVL (1691) GA этот показатель был достоверно ниже – 0,55→0,48 (р < 0,05). У пациенток при НО > 0,5 течение беременности было благоприятным. Более выраженная АПС-резистентность (НО ≤ 0,49) ассоциировалась с гестационными осложнениями. Заключение. Полученные данные по АПС-резистентности позволяют относить в группу высокого риска по тромботическим и акушерским осложнениям женщин – носительниц мутации фактора V Лейден (1691) не только с генотипом АА, но и с генотипом GA. AПС-резистентность ≤ 0,49 (по показателю НО) при носительстве мутации фактора V Лейден (1691) GA может рассматриваться как прогностический маркер развития гестационных осложнений с наибольшей точностью при сроке 7-8 недель беременности. Aim: to study during pregnancy the relationship between factor Va resistance to activated protein C (APC-resistance) in carriers of FVL gene mutation (1691) GA with clinical realization of thrombotic events and gestational complications such as preeclampsia, fetal growth retardation and miscarriage. Materials and methods. A prospective clinical cohort study of 1100 pregnant women was performed. Two cohorts were identified: main group – 500 patients with FVL genotype (1691) GA and control group – 600 women with FVL genotype (1691) GG. Results. The median of normalized ratio (NR) of APC resistance in the control group with FVL genotype (1691) GG ranged from 1.0→0.86. In pregnant women – the carriers of FVL genotype (1691) GA this parameter was significantly lower – 0.55→0.48 (р < 0.05). In patients with HO > 0.5 the course of pregnancy was favorable. More expressed APS-resistance (НО ≤ 0,49) was associated with gestational complications. Conclusion. The obtained data on APC-resistance allow to classify women – the carriers of Factor V Leiden (1691) mutation, not only with the AA genotype but also with GA genotype as the group of high risk for thrombotic and obstetric complications. APC resistance ≤ 0.49 (according NR) with the carriage of Factor V Leiden mutation (1691) GA can be considered as a prognostic marker for the development of gestational complications with the greatest accuracy at a period of 7-8 weeks of gestation.

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Risk of Pregnancy-Associated Venous Thromboembolism in Women with a History of Prior Thrombosis.

Blood ◽

10.1182/blood.v108.11.1493.1493 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1493-1493 ◽

Cited By ~ 1

Author(s):

Andrea Gerhardt ◽

Rudiger E. Scharf ◽

Rainer B. Zotz

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Gene Mutation ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Previous Episode ◽

Recurrent Venous Thromboembolism ◽

History Of ◽

Heparin Prophylaxis

Abstract Background: Previous estimates of the rate of recurrent venous thromboembolism (VTE) during pregnancy in women with a history of VTE have vary between 0 and 13%. Therefore, the decision to administer or withhold heparin - especially in the antepartum period - has been discussed controversial. In a recent study by Brill-Edwards et al. (N Engl J Med2000;343:1439–44), no recurrences of VTE occurred in women (n=44) who had a previous episode of thrombosis that was associated with a temporary risk factor and who also had no evidence of thrombophilia. Based on these results, antepartum heparin prophylaxis is not routinely recommended in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor (ACCP guidelines 2004). The objective of our study was to evaluate the risk of recurrent pregnancy-associated thrombosis in women with a history of VTE. Materials and Methods: We retrospectively studied 198 women with at least one pregnancy (275 pregnancies in total) after a one previous episode of VTE. Sixty-three women (81 pregnancies) were excluded from the analysis because of antepartum heparin prophylaxis. Results: In the subgroup of women without heparin prophylaxis (n=135), 15 (7.7%) thromboembolic events occurred antepartum in 194 pregnancies. Further subgroup analysis, stratified for the nature of first VTE, gave the following number of antepartum VTE per number of pregnancies: 2 VTE/19 pregnancies (10.5%) in 14 women (first VTE: immobilization), 4 VTE/33 pregnancies (12.1%) in 24 women (first VTE: surgery), 5 VTE/69 pregnancies (7.2%) in 46 women (first VTE: oral contraception), 2 VTE/58 pregnancies (3.4%) in 40 women (first VTE: pregnancy), 2 VTE/15 pregnancies (13%) in 11 women (first VTE: idiopathic). Nine of the 15 women with VTE (7/13 women with first VTE triggered by temporary risk factor; 2/2 women with first idiopathic VTE) had a heterozygous factor V Leiden G1691A or prothrombin G20210A gene mutation. In the postpartum period, 16 VTE in 194 pregnancies occurred after live birth in the 135 women without heparin prophylaxis. Nine of these 16 women had a heterozygous FVL or prothrombin G20210A gene mutation. In Conclusion, the risk of recurrent antepartum VTE was similar in women with and without factor V Leiden G1691A or the prothrombin G20210A gene mutation and did not differ between women with first VTE triggered by a transient risk factor or an idiopathic first VTE. In addition to recommended postpartum heparin prophylaxis, our data support the need for a routine antepartum prophylaxis in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor.

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Factor V Leiden and Prothrombin G20210A Gene Mutations Should Not Be Routinely Screened among Venous Thromboembolism (VTE) Patients in Singapore - This and Patterns of Other Thrombophilic Conditions among Our VTE Patients.

Blood ◽

10.1182/blood.v108.11.4087.4087 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4087-4087

Author(s):

Heng Joo Ng ◽

Lai Heng Lee ◽

Te-Chih Liu ◽

Lip Kun Tan ◽

Ponnudurai Kuperan

Keyword(s):

Gene Mutation ◽

Antithrombin Iii ◽

Gene Mutations ◽

Factor V Leiden ◽

Anticardiolipin Antibody ◽

Protein S ◽

Prothrombin G20210a ◽

Factor V ◽

Protein C Deficiency ◽

G20210a Mutation

Abstract Introduction: Emerging good quality evidence has suggested that the prevalence of VTE among Asians is significant and was largely underestimated previously. Objective and methods: We conducted a study of thrombophilic markers among our population of VTE patients to determine their prevalence and help determine the best screening strategy among our increasing number of VTE patients. Three major hospitals in the country were involved in this study. Results: Of 254 patients recruited, ethnic distribution was as follows: Chinese 68.1%, Malays 17.3%, Indians 12.6%, Others 2%. The ratio of males to females was 2:3. Major risk factors such as surgery, trauma and malignancy was recordedand identified in about 80% of the population. Twenty-one percent of patients had pulmonary embolism. Positive results of thrombophilic markers were as follows: protein C deficiency, 4 patients (1.52%); protein S deficency, 26 (10.24%), antithrombin III deficiency, 11 (4.33%); lupus anticoagulant, 9 (3.54%); anticardiolipin antibody IgG, 3 (1.18%); anticardiolipin antibody IgM, 6 (2.36%); hyperhomocysteinemia, 32 (12.6%); factor V Leiden gene mutation, 0 (0%); prothrombin 20210 gene mutation, 0 (0%). The prevalence of at least one thrombophilic condition was found in about one third of our patients. The relative risks of these thrombophilic conditions will be compared with a healthy control population. Conclusion: Among our VTE patients, the most commonly associated thrombophilic conditions were protein S and antithrombin III deficiencies. The factor V Leiden and prothrombin G20210A mutation did not feature at all in our patient population and is consistent with other studies on Asian populations. These tests should not be included as part of our thrombophilic screening.

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The Frequency of Factor V Leiden and Concomitance of Factor V Leiden With Prothrombin G20210A Mutation and Methylene Tetrahydrofolate Reductase C677T Gene Mutation in Healthy Population of Denizli, Aegean Region of Turkey

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029606298990 ◽

2007 ◽

Vol 13 (2) ◽

pp. 166-171 ◽

Cited By ~ 9

Author(s):

Sibel Kabukcu ◽

Nazan Keskin ◽

Ali Keskin ◽

Erol Atalay

Keyword(s):

Gene Mutation ◽

Factor V Leiden ◽

Mthfr C677t ◽

Prothrombin G20210a ◽

Healthy Population ◽

Factor V ◽

Aegean Region ◽

Apc Resistance ◽

G20210a Mutation ◽

Fv Leiden

Factor V Leiden causing activated protein C resistance is the most common inherited form of thrombophilia leading to thrombosis. Its frequency shows great ethnic and geographic variations. The aim of this study was to determine the frequency of FV Leiden and coinheritance of FV Leiden with two other frequent hereditary thrombophilia causes, namely, prothrombin G20210A and methylene-tetrahydrofolate reductase ( MTHFR) C677T mutation in the Aegean region of Turkey. The study population consisted of 1030 (500 men and 530 women) apparently healthy subjects. Functional resistance to activated protein C (APC) was measured by using the test kit STA staclot APC-R ((Diagnostica Stago, Asnieres, France, Cat. No. 00721). In subjects with APC resistance, molecular analyses of FV Leiden and of prothrombin G20210A and MTHFR C677T mutation were performed by using FV-PTH-MTHFR StripA (Vienna Lab, Labordiagnostika GmbH, Austria) kit, which was based on hybridization of polymerase chain reaction (PCR) amplified DNA products with mutation-specific oligonucleotide probes. Functional APC resistance was present in 93 subjects (9%). FV Leiden mutation was found in 87 of 93 subjects with APC resistance by PCR method. The FV Leiden carrier frequency was found to be 8.4% (87/1030). Seventy-six individuals were heterozygous (7.3%), and 11 were homozygous (1.06%). Among the 87 subjects with FV Leiden mutation, 45 subjects had MTHFR C677T gene mutation (7 homozygous, 38 heterozygous) and 4 subjects had heterozygote prothrombin G20210A gene mutation. A combination of FV Leiden and prothrombin G20210A and MTHFR C677T gene mutation was detected in 3 subjects. The results indicate that FV Leiden prevalence is quite high and coexistence of FV Leiden with other hereditary causes of thrombosis such as prothrombin G20210A mutation and MTHFR enzyme defect is not rare in healthy population of Aegean region of Turkey.

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Aetiology of pre-eclampsia and thrombophilic genetic mutations

Clinical Science ◽

10.1042/cs20030181 ◽

2003 ◽

Vol 105 (3) ◽

pp. 269-271 ◽

Cited By ~ 2

Author(s):

M. HAYASHI

Keyword(s):

Gene Mutation ◽

Intrauterine Growth Restriction ◽

Hellp Syndrome ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Genetic Mutations ◽

Factor V ◽

Intrauterine Growth ◽

Cytokine Imbalance ◽

Thrombophilic Mutations

Schlembach and co-workers in this issue of Clinical Science have studied the association of maternal and/or fetal factor V Leiden (FVL) and prothrombin G20210A gene mutation with HELLP syndrome and intrauterine growth restriction (IUGR) to confirm whether these genetic mutations are important risk factors for the pathogenesis of the HELLP syndrome, leading to an inadequate maternal–fetal circulation. Results showed that fetal FVL and prothrombin G20210A gene mutation were significantly associated with IUGR. The authors speculated that fetal thrombophilic mutations resulted in placental microthrombosis, leading to a disturbed fetoplacental blood flow. This study represents another important step in our understanding of the pathophysiological action of fetal thrombophilic mutations on fetal development. Regarding the aetiology of pre-eclampsia, one possible speculation is that systemic immune maladaptation, including systemic cytokine imbalance, contributes to placental ischaemia and systemic vessel abnormalities leading to pre-eclampsia.

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Associations of Coagulation Factor V Leiden and Prothrombin G20210A Mutations With Budd–Chiari Syndrome and Portal Vein Thrombosis: A Systematic Review and Meta-analysis

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2014.04.026 ◽

2014 ◽

Vol 12 (11) ◽

pp. 1801-1812.e7 ◽

Cited By ~ 57

Author(s):

Xingshun Qi ◽

Weirong Ren ◽

Valerio De Stefano ◽

Daiming Fan

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Factor V Leiden ◽

Coagulation Factor ◽

Prothrombin G20210a ◽

Factor V ◽

Budd Chiari Syndrome ◽

Vein Thrombosis ◽

Chiari Syndrome ◽

Coagulation Factor V

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A rare case of catastrophic antiphospholipid syndrome triggered by estrogen‐containing oral contraceptives in a patient with double heterozygous factor V Leiden and prothrombin G20210A mutations

American Journal of Hematology ◽

10.1002/ajh.26138 ◽

2021 ◽

Author(s):

Hannah L. McRae ◽

Annie H. Yang ◽

Karen Kruzer ◽

Glynis A. Scott ◽

Majed A. Refaai

Keyword(s):

Antiphospholipid Syndrome ◽

Oral Contraceptives ◽

Rare Case ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Catastrophic Antiphospholipid Syndrome

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Association of increased C-Reactive Protein and hypocomplementemia with risk factors for thrombosis in women who have susceptibility for poor gestational outcome; importance of preconceptional counseling

Human Antibodies ◽

10.3233/hab-210452 ◽

2021 ◽

pp. 1-6

Author(s):

Mehmet Sinan Beksac ◽

Hanife Guler Donmez

Keyword(s):

Risk Factors ◽

Inflammatory Diseases ◽

Factor V Leiden ◽

Care Program ◽

Prothrombin G20210a ◽

Study Group ◽

Factor V ◽

C Reactive Protein ◽

Mthfr Polymorphisms ◽

Reactive Protein

This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n= 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n= 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n= 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p= 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p= 0.386, p= 0.462, p= 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications.

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