Aetiology of pre-eclampsia and thrombophilic genetic mutations

2003 ◽  
Vol 105 (3) ◽  
pp. 269-271 ◽  
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.

Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

2003 ◽  
Vol 105 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Dietmar SCHLEMBACH ◽  
Ernst BEINDER ◽  
Juergen ZINGSEM ◽  
Ute WUNSIEDLER ◽  
Matthias W. BECKMANN ◽  
...  
Keyword(s):  
Blood Flow ◽  
Intrauterine Growth Restriction ◽  
Hellp Syndrome ◽  
Factor V Leiden ◽  
Growth Restriction ◽  
Control Group ◽  
Factor V ◽  
Intrauterine Growth ◽  
Prothrombin Mutation ◽  
Thrombophilic Mutations

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.

scholarly journals Hereditary thrombophilia and adverse pregnancy outcomes

2021 ◽  
Vol 64 (3) ◽  
pp. 68-77
Author(s):  
Valentin Friptu ◽  
◽  
Diana Mitryuk ◽  
Olga Popusoi ◽  
◽  
...  
Keyword(s):  
Gene Mutation ◽  
Pregnancy Outcomes ◽  
Intrauterine Growth Restriction ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Intrauterine Growth ◽  
Adverse Pregnancy

Background: Multiple studies have found a relatively increased risk of placenta-mediated pregnancy complications in women with congenital thrombophilia, especially early recurrent pregnancy loss, fetal loss, early-onset preeclampsia, intrauterine growth restriction, and premature abruption of normally positioned placenta. However, the extent of the association and the absolute risk are very modest, but they significantly increase in pregnant women with severe obstetric complications. Conclusions: There is convincing evidence that deficiency of natural anticoagulants (antithrombin, protein C, protein S) is a risk factor for late fetal loss. Factor V Leiden G1691A gene mutation and prothrombin G20210A gene mutation are associated with a double risk for early and unexplained recurrent pregnancy loss and for non-recurrent late fetal loss. The association of congenital thrombophilia with preeclampsia is much more uncertain, being probably limited factor V Leiden G1691A gene mutation and more severe cases of preeclampsia. Fewer data are available on intrauterine growth restriction (IUGR) and premature abruption of the normally positioned placenta. There is insufficient evidence to suggest an association of other forms of congenital thrombophilia with adverse pregnancy outcomes. In addition, genetic and epidemiological research suggests that placenta-mediated pregnancy complications are of polygenic multifactorial etiology, with a risk determined by the interaction of multiple genetic variants and other risk factors.

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

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1493-1493 ◽  
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.

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 ◽  
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.

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

2007 ◽  
Vol 13 (2) ◽  
pp. 166-171 ◽  
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.

scholarly journals Evaluation of pai-1 polymorphisms in central and peripheral thromboembolies

2021 ◽  
Vol 38 (2) ◽  
pp. 167-171
Author(s):  
Özge Arıcı DÜZ ◽  
Oktay OLMUŞÇELİK ◽  
Ali İhsan GEMİCİ ◽  
Özlem SAATÇİ SANCAKTEPE
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Vascular System ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Significant Difference ◽  
Medium Risk ◽  
Pai 1

Thromboembolism is a clinical finding that occurs due to thrombus; formed in the vascular system and has various etiological factors. It can be classified as central and peripheral thromboembolism. Our objective in this study is to explore genetic risk factors in central and peripheral thromboembolism and reveal the differences. 342 thromboembolism patients were retrospectively included to the study between January 2016 and December 2019. Demographic characteristics, risk factors for thromboembolism and genetic mutations in central and peripheral thromboembolism groups were overviewed. The genetic mutations evaluated in patients were Factor V Leiden G1691A, Factor V HR1299R, Factor II (Prothrombin) G20210A, MTHFR (Methylenetetrahydrofolate reductase) C677T, MTHFR A1298C, PAI 4G/5G. Within the scope of the study, genetic analyzes of 106 patients were reached and included in the study. Seventy-two central thromboembolism (69.8%), 34 (31.2%) peripheral thromboembolisms were detected. Sixty-three of the central thromboembolisms were from arterial and nine were from venous origin. There was no significant difference between age, gender and risk factors of central thromboembolism and peripheral thromboembolism patients (p˃0.05), but smoking was more common in central thromboembolism patients (p: 0.041). 4G/5G polymorphism was observed more frequently in patients with central thromboembolism (p: 0.039). Thromboembolism is a multifactorial disease, PAI-1 4G/5G polymorphism is a medium risk factor for thromboembolism. We conclude that PAI-1 4G/5G polymorphism is more frequent in central thromboembolism than peripheral thromboembolism and its evaluation can give more information about the thromboembolic risk analyze.

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