Impact of Inherited Thrombophilia Factors On Thrombotic Risk in Patients with Newly Diagnosed BCR- Abl (-) Myeloproliferative Disorders; Finally a Role of MTHFR- C677T Polymorphism?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5065-5065 ◽  
Author(s):  
Emmanouil Papadakis ◽  
Valia Papageorgiou ◽  
Konstantinos Tsepanis ◽  
Dionysia Theocharidou ◽  
Vassilios K Papadopoulos ◽  
...  
Keyword(s):  
Platelet Count ◽  
Myeloproliferative Neoplasms ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Thrombotic Risk ◽  
Mthfr C677t Polymorphism ◽  
Inherited Thrombophilia ◽  
The Impact

Abstract Abstract 5065 Introduction: Myeloproliferative Neoplasms (MPN) are commonly associated with thrombotic complications, which constitute the major cause for morbidity and mortality in these patients. While the pathogenesis of Thrombosis is not yet fully elucidated, the impact of inherited thrombophilia on MPN patients is unknown. MTHFR-C677T polymorphism is a usual variation of the MTHFR gene and exerts weak, if any, prothrombotic role mainly through increased homocysteine levels. Up to date there are no specific guidelines for treatment of thrombotic events in MPN patients. Objectives: The purpose of our study is to determine the impact of inherited thrombophilia factors on thrombotic risk in patients with newly diagnosed BCR- abl (-) myeloproliferative neoplasms. We also tried to assess the role of the MTHFR- C677T polymorphism in thrombotic risk in our MPN patients. Material and Methods: Our study population consisted of 68 patients diagnosed with BCR- abl (-) myeloproliferative neoplasms in the Hematology Department of our Hospital during the period 2005– 2008. Diagnosis was set according to the World Health Organization and Updated European Clinical and Pathological criteria for the Diagnosis, Clasification and Staging of the Philadelphia chromosome (-) chronic myeloproliferative disorders. Age, Sex, Platelet count, serum homocysteine levels, presence of Jak-2 mutation, together with genetic polymorphisms of Factor V-Leiden and FII- G121120A prothrombin mutations, and MTHFR- C677T polymorphism were assessed. Among our patients, whose median age was 65 years (range 21– 83), 40 were male and 28 female. 41 patients were diagnosed with essential thrombocythemia (ET), 22 with Polycythemia Vera (PV), 3 with essential myelofibrosis and 2 with Unclassified Chronic bcr- abl (-) MPN. Statistical analysis was conducted with SPSS 20. 0. At first a monovariate statistical model was used with significant level set at p= 0. 05. For the multivariable statistical analysis model we used all variables with p<0, 05 from the previous model and those mentioned at recent medical literature as significantly related with thrombotic risk. Results: From our patients, 31 suffered a thrombotic event (arterial or venous thrombosis, microvascular disorders). Regarding their thrombophilia profile patients were found to be: 4 carriers of the FVL mutation, 4 carriers of the FII- G121120A and 13 were carrying the MTHFR- C677T polymorphism. Moreover, 56 patients were tested for Jak-2V617F, and 42 of them were found to be positive (100% patients with P. V., 79% ET patients). We tried to define whether the following variables are high risk factors for thrombotic events in our population: Platelet count, serum homocystein levels, presence of Jak-2 mutation, Factor V-Leiden and FII- G121120A, mutations, and MTHFR- C677T. Surprisingly, the presence of MTHFR- C677T reached statistical significance on the monovariate analysis (p= 0. 001), while published data on general thrombosis population don't show any correlation of the MTHFR- C677T with thrombotic events. Jak-2 mutation was studied in a subgroup of patients, which didn't include patients with PV and was found to be statistically significant thrombosis risk factor in the monovariate analysis. Multiple regression analysis revealed MTHFR- C677T genetic polymorphism as independent risk factor concerning thrombotic events in patients with BCR- abl (-) MPNs (p= 0. 01, Exp (B)= 39. 227, 95%CI: 2. 41 –638. 547). The mean concentration of serum homocystein and the mean platelet count didn't show any statistically significant difference between patients carying MTHFR- C677T polymorphism and MTHFR- C677T negative patients. So serum homocystein levels and platelet count were not found to be confounding factors. In addition the co- existence of MTHFR- C677T with either G121120A or FVL mutations was detected in 4 patients, and all of them suffered from thrombotic events. Conclusions: Our study is the first to demonstrate a prothrombotic role of MTHFR- C677T polymorphism in a MPN population. Thrombophilia studies are needed in MPN patients in order to better assess the thrombotic risk for the patients but foremost to properly tailor anticoagulant treatment after a thrombotic episode. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of thrombophilia and waist circumference on the risk of venousthromboembolism

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T B Kondratieva ◽  
L V Popova ◽  
T V Khlevchuk ◽  
M Z Kanevskaya ◽  
M B Aksenova ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Waist Circumference ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Inherited Thrombophilia ◽  
Pai 1

Abstract Background Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) represents a major health problem. In the general population, the absolute risk of any kind of VTE is 0.1%–0.2% per year, and it increases with age. VTE is an important and preventable cause of morbidity and mortality, with almost a third of survivors experiencing long term effects. Obesity is well-known risk factor of VTE. The extent of the effects of obesity on VTE depends not only on total body fat, but also on the distribution of adipose tissue (e.g., central obesity) and the interplay among risk factors for VTE, such as genetic mutations, and other risk factors. Thrombophilia, venous thromboembolism, obesity, waist circumference Purpose The aim of this study is to investigate the impact of waist circumference on the risk of venous thromboembolism Methodology The study involved 68 patients with VTE (33 females and 34 males, mean age 56.8 years ±15.3) and 84 patients without VTE (38 males and 46 females, 44.4 years±18.6). From 2015 to 2017, data have been collected from records of patients admitted to department of internal medicine. All subjects were recruited to the study during their stay in the hospital. The reasons for hospitalization were: acute event of DVT or PE for the main group, the absence of acute event or history of VTE for the control group. DVT was diagnosed by ultrasonic Doppler examination, and PE was confirmed by intravenous radiocontrast computed tomography. Anthropometric measures were performed with subjects wearing short-sleeved garments and no shoes; waist circumference was measured in centimeters at the umbilical line. For all patients genetic testing for inherited thrombophilia – Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism – was performed by real-time PCR technique. Results Factor V Leiden G1691A increase the risk of VTE in 2.11 (CI: 1.79–2.48), p=0.049, prothrombin G20210A in 3.21 (CI: 1.66–6.211), p=0.049. MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism also increase the risk of VTE, but it was no significant. Study have shown that waist circumference &gt;80 cm increase the risk of VTE in 3.19 (CI: 1.35–7.58), p=0.019. Combination of inherited thrombophilia (Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism) and waist circumference &gt;80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p&lt;0.001. Conclusion Previous results of our work indicate influence of waist circumference &gt;80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference &gt;80 cm. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

2009 ◽  
Vol 33 (1) ◽  
pp. 102-107 ◽  
Author(s):  
Carlo Fabris ◽  
Pierluigi Toniutto ◽  
Edmondo Falleti ◽  
Elisabetta Fontanini ◽  
Annarosa Cussigh ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Alcohol Consumption ◽  
Mthfr C677t ◽  
Male Gender ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism

Abstract 3457: Methylenetetrahydrofolate Reductase Gene Polymorphism C677T And The Risk Of Premature Myocardial Infarction With “Normal” Coronary Arteries.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Loukianos Rallidis ◽  
Christoforos Komborozos ◽  
Argyri Gialeraki ◽  
Maria Zolindaki ◽  
Panagiotis Vavoulis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Methylenetetrahydrofolate Reductase ◽  
Young Patients ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Normal Coronary Arteries ◽  
Methylenetetrahydrofolate Reductase Gene Polymorphism ◽  
The Impact

Purpose: the pathogenetic mechanism of acute myocardial infarction (AMI) in young patients remains unknown. We explored the impact of homocysteine and its main genetic modulator Table 2 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients who sustained AMI under the age of 36 years. Methods: we recruited 136 consecutive patients who had survived their first AMI before the age of 36 years (mean age=32 ± 3.1 years, range 23–35 years, 121 men). Blood was taken for lipids and homocysteine levels within 12 hours from admission. The MTHFR C677T polymorphism was also determined with polymerase chain reaction. All patients underwent cardiac catheterization. One hundred-three healthy individuals without a family history of coronary heart disease (CHD), matched for age and sex served as controls. Results: coronary angiogram revealed significant CHD in 104 patients while 32 (23.5%) had no significant CHD. The prevalence of homozygotes for C677T polymorphism [T/T genotype] was 27.2% in patients and 14.6% in controls (p=0.02). In the subgroup of patients who had AMI and “normal” coronary arteries the frequency of homozygotes was 43.8% (p=0.001 versus controls and p=0.02 versus patients with significant CHD). The table presents lipids and homocysteine levels in AMI patients with “normal” coronary arteries and controls. Logistic regression model showed that the odds ratio for a young individual with T/T genotype to develop AMI with “normal” coronary arteries was 5.2 (confidence interval 1.2–23, p=0.03) adjusted for smoking habits, body mass index, hypertension and diabetes mellitus. Conclusions: the presence of homozygocity for MTHFR C677T polymorphism is associated with 5-fold higher risk for premature AMI with “normal” coronary arteries. This suggests that homocysteine may be involved in the formation of an obstructive thrombus in coronary arteries, especially in young individuals without significant underlying atheromatic burden.

Inherited and Acquired Thrombophilia in Children and Young Adults with Bcr-Abl Negative Chronic Myeloproliferative Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4949-4949
Author(s):  
Fiorina Giona ◽  
Giovanna Palumbo ◽  
Patrizia Pignoloni ◽  
Angela Amendola ◽  
Antonio Chistolini ◽  
...  
Keyword(s):  
Young Adults ◽  
Platelet Count ◽  
Mthfr C677t ◽  
Myeloproliferative Disorders ◽  
C677t Polymorphism ◽  
Hematocrit Level ◽  
Mthfr C677t Polymorphism ◽  
Chronic Myeloproliferative Disorders ◽  
G20210a Mutation ◽  
Children And Young Adults

Abstract Several associated thrombophilic abnormalities have been reported in adults with Bcr-Abl negative chronic myeloproliferative disorders (MPD), mostly essential thrombocythemia (ET) and polycythemia vera (PV), but sporadic data are available in younger patients (pts). In order to define coagulation abnormalities in very young pts, we evaluated thrombophilic parameters in MPD pts aged &lt;20 years (yrs) at diagnosis. Prothrombin time (PT), activated partial thromboplastin time (aPTT), lupus anticoagulant (KCT and dRVVT), functional protein C (PC), free protein S (PS) antigen, functional antithrombin (AT), homocysteine (HCY), factor V Leiden (FVL) mutation, factor II (FII) G20210A mutation and methylentethrahydrofolate reductase (MTHFR) C677T polymorphism were investigated. Thirty-two MPD pts (16 males and 16 females) with a median age of 166/12 yrs (range: 3mo-1911/12 yrs) diagnosed at the study Institution between March 1980 and February 2005 were tested after informed consent of pts or parents. Twenty-five had a diagnosis of ET (7 familial forms) and 5 had PV, according to the criteria of the PV Study Group; in 2, a diagnosis of MPD with thrombocytosis and erythrocytosis was made. Cytogenetic and molecular studies were normal in all cases. At diagnosis, median platelet count for ET and MPD pts was 1,184 x 109/L (range 611–2,640); median hematocrit level for PV and MPD pts was 54% (range 52–72%). Among the ET cohort, 6 asymptomatic pts received no treatment, 4 were treated with aspirin alone and 15 received cytoreductive therapy. PV and MPD pts were phlebotomized to maintain a hematocrit level &lt;50%. Median interval between diagnosis and the time of the study was 8.8 yrs (range: 1 mo – 24 yrs ). No thrombotic events occurred. Four female ET became pregnant and had 4 children, 1 of them being affected by familial thrombocythemia. At the time of the coagulation study, median platelet count for ET and MPD pts was 695 x 109/L (range 325–1,120); the median hematocrit level for those with PV and MPD was 53% (range 52–60.5%). Increased PT and aPTT ratios (n.v. &lt;1.14 and &lt;1.16) were observed in 8/32 (20%) and 16/32 (50%) pts, combined in 7. KCT ratio (n.v. &lt;1.31) was increased in 4/31 (13%) pts, while the dRVVT ratio was normal in 31/31 tested pts. Functional PC and free PS levels were decreased in 3/30 (10%) and 3/31 (10%) tested pts, respectively. AT levels were normal in all pts (32/32). An increased HCY level was found in 1 PV pt. Of the 27 pts investigated for FVL, FII G20210A mutations and MTHFR C677T polymorphism, 1 ET pt was heterozygous for both the FVL and FII G20210A mutations, 1 ET pt was heterozygous for both MTHFR C677T polymorphism and FII G20210A mutation. One ET pt showed an isolated FII G20210A mutation. Screening for the C677T polymorphism in the MTHFR gene revealed that 18 pts (66.5%) were heterozygous, 15 of them affected by ET (7 with the familial form). In our MPD population of children and young adults, the frequencies of heterozygosis of FII G20210A mutation (3/27 pts = 11%) and MTHFR C677T polymorphism (66.5%) were higher than those reported in the normal population (about 2.5% and 45%, respectively). Larger multicenter studies are required to further extend these observations.

The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients

2017 ◽  
Vol 18 (8) ◽  
pp. 787-795 ◽  
Author(s):  
Loes Lambrecht ◽  
Charlotte Sleurs ◽  
Veerle Labarque ◽  
Catharina Dhooge ◽  
Annouschka Laenen ◽  
...  
Keyword(s):  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Pediatric Osteosarcoma

Plasma Homocysteine Levels, Methelene TetraHydroFolate Reductase (MTHFR) Polymorphism, and the Risk of Thromboembolism in Children: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5351-5351
Author(s):  
Akash Nahar ◽  
Yaddanapudi Ravindranath ◽  
Jeanne M. Lusher ◽  
Meera B. Chitlur ◽  
Mary Jane Frey ◽  
...  
Keyword(s):  
Risk Factor ◽  
Demographic Data ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Standard Laboratory ◽  
Normal Range ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Normal Ranges

Abstract Introduction: Hyperhomocystenemia (HHcy) has been identified as a moderate risk factor for thrombosis in adults. A polymorphism in the folate-metabolizing enzyme Methelene TetraHydroFolate Reductase (MTHFR) has been implicated in causing a mild to moderate elevation in homocysteine (Hcy). Data on the role of HHcy and MTHFR polymorphism in pediatric thromboembolism (TE) are sparse. We reviewed, in our series of 125 patients, the role of elevated Hcy and MTHFR C677T polymorphism as a risk factor for TE in children. Materials and Methods: Inpatient and outpatient clinic charts of patients with documented TE, followed at the Hemostasis and Thrombosis Center at Children’s Hospital of Michigan were reviewed for demographic data, Hcy level and the presence of the MTHFR C677T polymorphism. Hcy levels were recorded at the time of diagnosis. Normal Hcy levels were defined both as per the standard laboratory normal range and established age-specific normal ranges available from literature. The 97.5% value was taken as the upper normal range. The data were thus analyzed separately with both stratifications. Results: A total of 171 patient charts were reviewed from January 1989 to June 2008. Hcy and MTHFR data were available on 125 patients. Thus, a total of 125 patients with a documented venous and/or arterial TE (60 venous and 45 arterial) were analyzed. 61 were females and 64 males. Mean age of presentation was 14 years (range of 1 day to 30 years). When no age segregation was done, normal Hcy plasma concentration was taken as 4 – 12 μmol/L for all ages. Elevated Hcy (&gt;12 μmol/L) was seen in a total of 8 patients (6.5 %), out of which 5 had CT genotype and 3 had the CC genotype. None of these patients were homozygous (TT) for the MTHFR polymorphism (Table 1). When the HHcy was analyzed by stratifying normal Hcy ranges based on age (Table 2), total of 15 patients (12%) were found to have elevated Hcy. Six patients had CT genotype and 9 patients had CC genotype. Again, none of the homozygote for MTHFR polymorphism had an elevated Hcy even after stratifying by age. Seven patients were homozygous with TT genotype, 49 patients had the CT genotype and the reminder 69 had normal CC genotype. The median homocysteine levels in these three groups were 5.7 μmol/L (4.3 – 8.5); 6 μmol/L (3–49.1) and 6.5 μmol/L (1.2 – 19.1) respectively (Table 3). Of the 6 patients with CT genotype and elevated homocysteine, 3 patients had end stage renal disease and the corresponding homocysteine levels were 18.3 μmol/L, 18.8 μmol/L and 49.1 μmol/L. Conclusions: HHcy was a risk factor in 8 out of 125 patients (6.5%) when the normal range was based on standard laboratory normal range and in 15 out of 125 (15%) when age stratified normal ranges were used. There was no difference in the median Hcy levels in patients with CC, CT or TT genotype for MTHFR polymorphism. Our data suggest that MTHFR polymorphism is not associated with elevation in Hcy and is not a risk factor in pediatric TE. Thus, genetic testing for MTHFR C677T polymorphism in pediatric patients with TE may not be justified at this time.

scholarly journals COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 903
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh
Keyword(s):  
Hospital Setting ◽  
Pathophysiological Mechanism ◽  
Systemic Response ◽  
Respiratory Complications ◽  
Thrombotic Risk ◽  
Global Pandemic ◽  
The Impact ◽  
Multiple Variants ◽  
Roll Out

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

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