scholarly journals Carrier frequencies for thrombophilia-related genetic variants in a Romanian cohort

2021 ◽  
Vol 26 (1) ◽  
pp. 2275-2282
Author(s):  
SIMONA TOPOLEANU ◽  
CRISTINA MAMBET ◽  
LUMINITA MARUTESCU ◽  
FLORENTINA IVAN ◽  
IRINA ALINA CUCU ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Plasma Homocysteine ◽  
High Rate ◽  
Prothrombin G20210a ◽  
Carrier Status ◽  
Factor V ◽  
Mthfr C677t Polymorphism ◽  
G20210a Mutation ◽  
Homozygous Genotype ◽  
The Impact

Genetic testing for hereditary thrombophilia, an inherited predisposition to thrombotic events, is increasingly available. To evaluate the rate of positive thrombophilia tests in our laboratory we analyzed the carrier status for common thrombophilia-related gene variants in a consecutive unselected cohort of 360 Romanian patients. Genetic tests were performed on a Real-Time PCR platform. Majority of patients (98.6%) carried at least one thrombophilic variant. The carrier frequencies for classical prothrombotic mutations in F5 (Factor V Leiden) and F2 genes (prothrombin G20210A mutation) were 11.67% (10.27% heterozygous, 1.4% homozygous) and 6.95% (6.39% heterozygous, 0.56% homozygous), respectively. Concurrently, high carrier frequencies for MTHFR c.677C>T, MTHFR c.1298A>C, and PAI-1 4G/5G variants, that are controversially associated with thrombophilia, were observed: 65.28% (52.5% heterozygous, 12.78% homozygous), 53.61% (45% heterozygous, 8.61% homozygous), and 78.61% (49.44% heterozygous, 29.17% homozygous), respectively. The impact of MTHFR genotypes on plasma homocysteine levels was also determined. Male carriers of TT homozygous genotype and CT heterozygous genotype of MTHFR C677T polymorphism had significantly higher levels of plasma homocysteine unrelated to age, compared to those harboring CC homozygous genotype (P=0.028). In unselected patients a high rate of positive thrombophilia tests was observed and the clinical implications of such results need to be carefully examined.

Prothrombotic Genetic Risk Factors and the Occurrence of Gestational Hypertension with or without Proteinuria

1999 ◽  
Vol 81 (03) ◽  
pp. 349-352 ◽  
Author(s):  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Giuseppe Cappucci ◽  
Natale Sciannamé ◽  
Sergio Montanaro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gestational Hypertension ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Carrier Status ◽  
Factor V ◽  
Mthfr Polymorphism ◽  
Confounding Variables ◽  
Fv Leiden ◽  
The Impact

SummaryGestational hypertension with or without proteinuria is a multi-factorial disease in which the presence of a hypercoagulable state has been suggested. The prothrombin G20210A, the Factor V (FV) Leiden mutations, and the C677T 5-10 methylenetethrahydrofolate reductase (MTHFR) polymorphism were investigated in 140 women with gestational hypertension and in 216 normotensive women from Southern Italy. Nine controls (4.1%) and 16 cases (11.4%; OR: 2.96, 95% CI: 1.27-6.91) carried the prothrombin A20210 allele. FV Leiden mutation was observed in 4 controls (1.8%) and 11 cases (7.9%; OR: 4.53, 95% CI: 1.41-14.53). The TT MTHFR genotype was found in 36 controls (16.6%) and 34 cases (24.4%; OR: 1.61, 95%CI: 0.96-2.74). The impact of potential confounding variables was evaluated using a logistic regression analysis. Nulliparity, Factor V Leiden and prothrombin A20210 carrier status resulted to be independent risk factors of having gestational hypertension with or without proteinuria. Imbalance of haemostasis, through prothrombotic genetic factors, may predispose to the occurrence of gestational hypertension.

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Lea Weingarz ◽  
Marc Schindewolf ◽  
Jan Schwonberg ◽  
Carola Hecking ◽  
Zsuzsanna Wolf ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Younger Patients ◽  
Risk Of Recurrence ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1686-1692 ◽  
Author(s):  
Rory R. Koenen ◽  
Guido Tans ◽  
René van Oerle ◽  
Karly Hamulyák ◽  
Jan Rosing ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Healthy Population ◽  
Factor V ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractProtein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa–based one-stage clotting assay was developed that enables quantification of the APC-independent activity of protein S in plasma from the ratio of clotting times (protein S ratio [pSR]) determined in the absence and presence of neutralizing antibodies against protein S. The pSR was 1.62 ± 0.16 (mean ± SD) in a healthy population (n = 60), independent of plasma levels of factors V, VIII, IX, and X; protein C; and antithrombin, and not affected by the presence of factor V Leiden. The pSR strongly correlates with the plasma level of protein S and is modulated by the plasma prothrombin concentration. In a group of 16 heterozygous protein S–deficient patients, the observed mean pSR (1.31 ± 0.09) was significantly lower than the mean pSR of the healthy population, as was the pSR of plasma from carriers of the prothrombin G20210A mutation (1.47 ± 0.21; n = 46). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation.

The Association Between Parameters of Erythrocytes Morphology and Thrombophilia-Related Mutations

2021 ◽  
Vol 16 ◽  
Author(s):  
Ozlem Oz ◽  
Ataman Gonel
Keyword(s):  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Cross Sectional ◽  
Factor V Leiden Mutation ◽  
Erythrocyte Morphology ◽  
Mthfr A1298c ◽  
G20210a Mutation ◽  
History Of

Background: Alterations in erythrocyte morphology parameters have been identified and associated with hematological disorders and other chronic and cardiovascular diseases. Erythrocytes are abundant in thrombus content. Their hemoglobin density and differences in the ratio of macrocytic and microcytic cells may be associated with hypercoagulopathy in those with a history of thrombosis. Objective: This cross-sectional study aimed to investigate the relationship between hemogram parameters and thrombophilia genetic parameters. Method: A total of 55 patients whose thrombophilia panel was reviewed due to the diagnosis of thrombosis were included in the study. %MIC, %MAC, %HPO, %HPR and all hemogram parameters were measured using Abbott Alinity HQ. Prothrombin G20210A, MTHFR C677T, MTHFR A1298C, Factor V Leiden G169A and PAI-1 4G/5G mutations were studied using Real Time-PCR. Results: The MTHFR C677T mutation was detected in 58.2% of the patients. The Factor V Leiden mutation was detected in 5.5% of the patients. The MTHFR A1298C mutation was detected in 58.2%, The PAI mutation was detected in 74.5%, and the Factor 13 mutation was detected in 29% of the patients. Prothrombin G20210A mutation was not detected in any of the patients. Red blood cell (RBC) and Hct values were higher in Factor 13 mutant group; the Hgb and Htc values were higher in the MTHFR C677T mutant group. Conclusion: The MTHFR C677T and Factor 13 mutations may be associated with high Hct and RBC, Hgb, and Htc values, respectively and coagulation tendency in patients with a history of thrombosis.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity

2020 ◽  
Vol 19 ◽  
pp. 127-130
Author(s):  
Jeske J.K. van Diemen ◽  
Jeske M. Bij de Weg ◽  
Arda Arduç ◽  
Olivier Veraart ◽  
David Mager ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Relationship Of ◽  
The Relationship

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2055-2061 ◽  
Author(s):  
Elizabeth F. W. van Vlijmen ◽  
Nic J. G. M. Veeger ◽  
Saskia Middeldorp ◽  
Karly Hamulyák ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Contraceptive ◽  
Factor V Leiden ◽  
Informed Choice ◽  
Rational Approach ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractCurrent guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.

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