Circulating microparticles in carriers of prothrombin G20210A mutation

SummaryFactor V Leiden (FVL) and prothrombin gene mutation G20210A (PTM) are the two most common genetic polymorphisms known to predispose carriers to venous thromboembolism (VTE). A recent study in FVL carriers showed that circulating levels of microparticles (MP) may contribute to their thrombogenic profile. To further elucidate the prothrombotic state linked to genetic thrombophilia, we extended this study to carriers of PTM. The plasma level of annexin V-MP, endothelial- MP (EMP), platelet-MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) was measured in 124 carriers of PTM (105 heterozygous and 19 homozygous) and in 120 age- and gender-matched healthy individuals. Heterozygous and homozygous carriers of PTM showed significantly increased levels of annexin V-MP (2930 [1440–4646] MP/μl and 3064 [2412–4906] MP/μl, respectively) and significantly shorter PPL clotting time (54 [46–67] sec and 55 [46–64] sec) compared to controls (1728 [782–2122] MP/μl and 71 [61–75] sec, respectively; p<0.01). Similarly, heterozygous and homozygous subjects presented with significantly higher levels of EMP, PMP and TF+ than controls (p<0.05). PTM carriers with a VTE history had significantly higher MP numbers and activity than controls. No significant difference was seen between carriers with and without a VTE history. We conclude that the higher levels of circulating MP found in PTM carriers may play a role in the development of VTE possibly by increasing thrombin generation. Further studies are needed to better define the role of MP as triggering factors for the thrombotic complications characterizing mild genetic thrombophilic defects.

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Circulating microparticles in carriers of factor V Leiden with and without a history of venous thrombosis

Thrombosis and Haemostasis ◽

10.1160/th12-05-0280 ◽

2012 ◽

Vol 108 (10) ◽

pp. 633-639 ◽

Cited By ~ 16

Author(s):

Elena Campello ◽

Luca Spiezia ◽

Claudia M. Radu ◽

Maria Bon ◽

Sabrina Gavasso ◽

...

Keyword(s):

Factor V Leiden ◽

Annexin V ◽

Factor V ◽

Thrombotic Risk ◽

Study Results ◽

Significant Difference ◽

Circulating Microparticles ◽

Venous Thromboembolic ◽

The Mean ◽

And Gender

SummaryAlthough factor V Leiden (FVL) is a major determinant of thrombotic risk, the reason why less than 10% of carriers eventually develop venous thromboembolic (VTE) events is unknown. Recent observations suggest that circulating levels of microparticles (MP) may contribute to the thrombogenic profile of FVL carriers. We measured the plasma level of annexin V-MP (AMP) platelet-MP (PMP), endothelial-MP (EMP), leukocyte-MP (LMP) and tissue factor-bearing MP (TF+MP), and the MP procoagulant activity (PPL) in 142 carriers of FVL (of these 30 homozygous and 49 with prior VTE), and in 142 age and gender-matched healthy individuals. The mean (± SD) level of AMP was 2,802 ± 853 MP/ μl in carriers and 1,682 ± 897 in controls (p<0.0001). A statistically significant difference between homozygous and heterozygous carriers of FVL was seen in the level of PMP, EMP and LMP, but not in that of the remaining parameters. When the analysis was confined to carriers with and without a VTE history, the mean level of AMP was 3,110 ± 791 MP/ μl in the former, and 2,615 ± 839 MP/μl in the latter (p<0.005). The mean level of all subtypes of circulating MP showed a similar pattern. The PPL clotting time was 39 ± 9 seconds (sec) in carriers, and 52 ± 15 sec in controls (p=0.003); and was 35 ± 8 sec in carriers with prior thrombosis, and 41 ± 10 sec in thrombosis-free carriers (p<0.005). Our study results suggest that circulating MP may contribute to the development of thrombosis in carriers of FVL mutation.

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

Blood ◽

10.1182/blood-2003-02-0620 ◽

2003 ◽

Vol 102 (5) ◽

pp. 1686-1692 ◽

Cited By ~ 16

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.

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

Reviews on Recent Clinical Trials ◽

10.2174/1574887116666211123092603 ◽

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.

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The Factor V Leiden Mutation and the Prothrombin G20210A Mutation Was not Found in Japanese Patients with Pulmonary Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614913 ◽

1999 ◽

Vol 82 (12) ◽

pp. 1769-1769 ◽

Cited By ~ 14

Author(s):

M. Hara ◽

A. Takada ◽

A. Ro

Keyword(s):

Pulmonary Thromboembolism ◽

Factor V Leiden ◽

Japanese Patients ◽

Prothrombin G20210a ◽

Factor V ◽

Factor V Leiden Mutation ◽

G20210a Mutation

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Upper Extremity Deep Vein Thrombosis in a Young Patient Double Heterozygous for Factor V Leiden and Prothrombin G20210A Mutation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960100700114 ◽

2001 ◽

Vol 7 (1) ◽

pp. 72-74 ◽

Cited By ~ 2

Author(s):

Amparo Vayá ◽

Jose Todolí ◽

Jose Ricart ◽

Amparo Estellés ◽

Yolanda Mira ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Young Patient ◽

Upper Extremity ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Vein Thrombosis ◽

G20210a Mutation ◽

Deep Vein

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

Pregnancy Hypertension ◽

10.1016/j.preghy.2020.01.008 ◽

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

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Contraception-Related Deep Venous Thrombosis and Pulmonary Embolism in a 17-Year-Old Girl Heterozygous for Factor V Leiden, Prothrombin G20210A Mutation, MTHFR C677T and Homozygous for PAI-1 Mutation: Report of a Family with Multiple Genetic Risk Factors and Review of the Literature

Pathophysiology of Haemostasis and Thrombosis ◽

10.1159/000319051 ◽

2009 ◽

Vol 37 (1) ◽

pp. 24-29 ◽

Cited By ~ 5

Author(s):

Jasna Lenicek Krleza ◽

Gordana Jakovljevic ◽

Ana Bronic ◽

Désirée Coen Herak ◽

Aleksandra Bonevski ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Embolism ◽

Genetic Risk ◽

Factor V Leiden ◽

Mthfr C677t ◽

Prothrombin G20210a ◽

Factor V ◽

Review Of The Literature ◽

G20210a Mutation ◽

Pai 1

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

Blood ◽

10.1182/blood-2011-03-345678 ◽

2011 ◽

Vol 118 (8) ◽

pp. 2055-2061 ◽

Cited By ~ 48

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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