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

2012 ◽  
Vol 108 (10) ◽  
pp. 633-639 ◽  
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.

Circulating microparticles in carriers of prothrombin G20210A mutation

2014 ◽  
Vol 112 (09) ◽  
pp. 432-437 ◽  
Author(s):  
Elena Campello ◽  
Luca Spiezia ◽  
Claudia Radu ◽  
Sabrina Gavasso ◽  
Patrizia Zerbinati ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Annexin V ◽  
Prothrombin G20210a ◽  
Factor V ◽  
G20210a Mutation ◽  
Significant Difference ◽  
Circulating Microparticles ◽  
Thrombotic Complications ◽  
Prothrombin Gene Mutation ◽  
And Gender

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.

The Relationship between Circulating Microparticles and Complications of Pregnancy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4028-4028
Author(s):  
Ophira Salomon ◽  
Rima Dardik ◽  
Ben-Zion Katz ◽  
David M. Steinberg ◽  
Reuven Achiron ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Pregnancy Complications ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Study Groups ◽  
Phosphatidyl Serine ◽  
Factor V ◽  
Singleton Pregnancy ◽  
Significant Difference ◽  
Circulating Microparticles

Abstract Uteroplacental thrombosis has been implicated in the pathogenesis of fetal loss, intrauterine growth restriction (IUGR) and preeclampsia. The role of inherited and acquired thrombophilias in such pregnancy complications is controversial. Recently, increased levels of circulating procoagulant microparticles (MPs) were related to fetal loss and preeclampsia (Laude et al. Thromb Haemost2001;85:18, Gonzalez-Quintero et al. Am J Obstet Gynecol2004;191:1418)). In this study, we measured the level of MPs derived from endothelial cells, platelets, and monocytes by flow cytometry using monoclonal antibodies against CD31, CD41 and CD14, respectively in 262 healthy unrelated primipara with a spontaneous singleton pregnancy. Expression of tissue factor by a monoclonal antibody and phosphatidyl serine by annexin 5 on MPs were also measured. All women were followed from the 24th week of gestation until delivery and IUGR, small for gestational age (SGA) at birth, pregnancy induced hypertension (PIH) or preeclampsia (PE) or none of the above were recorded. Blood sampling was carried out at 24th week of gestation. The levels of CD31 and CD41- positive MPs in women with and without the above pregnancy complications are presented in the table. Not shown are values of CD14, annexin 5 or tissue factor on MPs since their median levels were negligible in all study groups. There was no statistically significant difference in CD31 and CD41- positive MPs between women who developed or not the indicated pregnancy complications. Also, there was no significant difference in levels of these MPs between women with and without the common inherited thrombophilias, factor V Leiden and or prothrombin mutation (28 patients) and lupus anticoagulant (10 patients). These data indicate that measurement of the level of MP at the 24th week of gestation has no predictive value for development of PIH, PE, IUGR or SGA. CD31 CD41 Number Median % p Median % p PIH or PE No 226 1.50 0.22 1.80 PIH Yes 13 1.57 3.07 0.53 PE Yes 22 0.62 1.87 IUGR No 207 1.53 0.13 1.95 0.08 IUGR Yes 32 1.30 1.71 SGA No 232 1.48 0.64 1.85 0.81 SGA Yes 26 1.27 2.24

scholarly journals Evaluation of the relation between myopia and central corneal thickness in patients admitted to vali-e-asr hospital in birjand, iran

2021 ◽  
pp. 138-143
Keyword(s):  
Central Corneal Thickness ◽  
Corneal Thickness ◽  
Epidemiologic Study ◽  
T Test ◽  
P Value ◽  
Study Results ◽  
Significant Difference ◽  
The Mean ◽  
And Gender ◽  
The Right

Introduction: Considering the increasing prevalence of myopia and the subsequent complications, and due to the dearth of studies on the correlation between myopia and gender with corneal thickness in Iran, this study aimed to determine this relationship in patients admitted to the ophthalmic clinic of Vali-e-Asr Hospital, Birjand, Iran. Methods: This descriptive-analytic epidemiologic study was conducted on 100 patients admitted to Vali-e-Asr ophthalmic clinic in Birjand, Iran, for one year since January 2017. According to the degree of myopia, the patients were divided into three groups of low (0-3 D), moderate (3-6 D), and high myopia (6≤D). Corneal thickness was measured using Orbscan and Pentacam. The data were analyzed in SPSS software (Version 19) through ANOVA and T-test to determine the possible relationship between myopia and central corneal thickness. A p-value equal to and less than (P≤0.05) was considered statistically significant. Results: Overall, 100 patients (49 males and 51 females) were enrolled in this study. Moderate myopia had the highest frequency in both eyes. The results of the T-test revealed that no significant difference was observed in the mean corneal thickness measured by Pentacam between the two genders (P=0.18 in the right eye and P=0.32 in the left eye). Based on the ANOVA findings, the mean corneal thickness measured by Pentacam was not significantly different among the myopia categories (P=0.05 in the right eye and P=0.51 in the left eye) Conclusions: The study results revealed that there was no significant relationship between myopia and gender with corneal thickness.

scholarly journals Thrombophilia genetic testing in Romanian young women with acute thrombotic events: role of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and A1298C polymorphisms / Evaluarea genetică a trombofiliilor la femei tinere din România cu evenimente acute trombotice: rolul Factorului V Leiden, Protrombinei G20210A, polimorfismelor MTHFR C677T și A1298C

2016 ◽  
Vol 24 (3) ◽  
pp. 291-305 ◽  
Author(s):  
Ana Maria Daraban ◽  
Adrian Pavel Trifa ◽  
Radu Anghel Popp ◽  
Diana Botezatu ◽  
Marinela Șerban ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Young Women ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Thrombotic Risk ◽  
Mthfr Polymorphisms ◽  
Mthfr A1298c ◽  
Significant Difference

Abstract Objective: The present case-control study aimed at evaluating the contribution of thrombophilic polymorphisms to acute venous (VTE) as well as arterial thrombotic events (ATE) in a population of young women with few traditional thrombotic factors (CVRF). Methods: We consecutively enrolled patients under 45 years of age, with less than 3 CVRF, evaluated for VTE or ATE, women and men as a comparator. The control group consisted of healthy young women. A thrombophilia panel and genetic testing for Factor V Leiden (FVL), G20210A Prothrombin and MTHFR polimorphisms were done. Results: A total of 323 persons were enrolled: 71 women and 121 men with thromboembolic events, and 131 healthy female as controls. Hyperhomocysteinemia was more frequent in ATE (30.4%) than VTE female patients (6.25%), p<0.01. Genetic testing was available in 45 women and 84 men with acute thrombotic events and in all controls. Homozygous FVL was associated with VTE in young women (10.3% vs 0% controls, p<0.01). Prothrombin G20210A polymorphism had the lowest prevalence – 5.4% and only heterozygosity was found. MTHFR C677T heterozygosity showed no significant difference between women patients and controls (62.2 % vs 43.5% respectively, p=0.1). The homozygous status, less frequent (6.6%), was not associated with ATE or VTE. Homozygous MTHFR A1298C was associated with VTE in women (17.2% patients vs 4.5% controls, OR 4.34, p 0.02, CI 1.22-15.3). Conclusion: In young women with few CVRF, mild hyperhomocysteinemia, homozygosity for FVL and for MTHFR A1298C polymorphisms increase the risk for VTE but not ATE. MTHFR polymorphisms are found with increased frequency in both healthy persons and patients therefore, their significance as an important thrombotic risk modifier remains unclear.

“Pseudo Homozygous” Activated Protein C Resistance due to Double Heterozygous Factor V Defects (Factor V Leiden Mutation and Type I Quantitative Factor V Defect) Associated with Thrombosis: Report of Two Cases Belonging to Two Unrelated Kindreds

1996 ◽  
Vol 75 (03) ◽  
pp. 422-426 ◽  
Author(s):  
Paolo Simioni ◽  
Alberta Scudeller ◽  
Paolo Radossi ◽  
Sabrina Gavasso ◽  
Bruno Girolami ◽  
...  
Keyword(s):  
Protein C ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Type I ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Apc Resistance ◽  
Quantitative Factor

SummaryTwo unrelated patients belonging to two Italian kindreds with a history of thrombotic manifestations were found to have a double heterozygous defect of factor V (F. V), namely type I quantitative F. V defect and F. V Leiden mutation. Although DNA analysis confirmed the presence of a heterozygous F. V Leiden mutation, the measurement of the responsiveness of patients plasma to addition of activated protein C (APC) gave results similar to those found in homozygous defects. It has been recently reported in a preliminary form that the coinheritance of heterozygous F. V Leiden mutation and type I quantitative F. V deficiency in three individuals belonging to the same family resulted in the so-called pseudo homozygous APC resistance with APC sensitivity ratio (APC-SR) typical of homozygous F. V Leiden mutation. In this study we report two new cases of pseudo homozygous APC resistance. Both patients experienced thrombotic manifestations. It is likely that the absence of normal F. V, instead of protecting from thrombotic risk due to heterozygous F. V Leiden mutation, increased the predisposition to thrombosis since the patients became, in fact, pseudo-homozygotes for APC resistance. DNA-analysis is the only way to genotype a patient and is strongly recommended to confirm a diagnosis of homozygous F. V Leiden mutation also in patients with the lowest values of APC-SR. It is to be hoped that no patient gets a diagnosis of homozygous F. V Leiden mutation based on the APC-resi-stance test, especially when the basal clotting tests, i.e., PT and aPTT; are borderline or slightly prolonged.

Detection of Circulating Tissue Factor and Factor VII in a Normal Population

1996 ◽  
Vol 75 (05) ◽  
pp. 772-777 ◽  
Author(s):  
Sybille Albrecht ◽  
Matthias Kotzsch ◽  
Gabriele Siegert ◽  
Thomas Luther ◽  
Heinz Großmann ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Normal Population ◽  
Mean Value ◽  
Factor Vii ◽  
Significant Difference ◽  
Age Dependent ◽  
The Mean ◽  
Highly Correlated ◽  
And Gender

SummaryThe plasma tissue factor (TF) concentration was correlated to factor VII concentration (FVIIag) and factor VII activity (FVIIc) in 498 healthy volunteers ranging in age from 17 to 64 years. Immunoassays using monoclonal antibodies (mAbs) were developed for the determination of TF and FVIIag in plasma. The mAbs and the test systems were characterized. The mean value of the TF concentration was 172 ± 135 pg/ml. TF showed no age- and gender-related differences. For the total population, FVIIc, determined by a clotting test, was 110 ± 15% and the factor VIlag was 0.77 ± 0.19 μg/ml. FVII activity was significantly increased with age, whereas the concentration demonstrated no correlation to age in this population. FVII concentration is highly correlated with the activity as measured by clotting assay using rabbit thromboplastin. The ratio between FVIIc and FVIIag was not age-dependent, but demonstrated a significant difference between men and women. Between TF and FVII we could not detect a correlation.

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

Polymorphisms in the protein C gene as risk factor for venous thrombosis

2009 ◽  
Vol 101 (01) ◽  
pp. 62-67 ◽  
Author(s):  
Carine Doggen ◽  
Hans Vos ◽  
Pieter Reitsma ◽  
Frits Rosendaal ◽  
Elisabeth Pomp
Keyword(s):  
Oral Contraceptive ◽  
Venous Thrombosis ◽  
Protein C ◽  
Contraceptive Use ◽  
Factor V Leiden ◽  
Factor V ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Oral Contraceptive Use ◽  
Increased Risk

SummaryProtein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

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.

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