scholarly journals Molecular Analysis of Factor V, Prothrombin and Methylenetetrahydrofolate Redutase in Thrombolic Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5050-5050
Author(s):  
Aldair Sousa Paiva ◽  
Hugo Diogenes De Oliveira Paiva ◽  
Geraldo Barroso Cavalcanti ◽  
Gioconda DR Leão ◽  
Marcos Dias Leão ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Factor V ◽  
Hereditary Risk ◽  
Hemostatic System ◽  
Pcr Rflp ◽  
Prothrombin Gene ◽  
Detection Of Mutations

Abstract Background: The study of thrombotic events requires knowledge of changes in the hemostatic system associated with multiple acquired and hereditary risk factors that suggest predisposition to thrombosis. The factor V or Leiden (G1621A), Prothrombin (G21210A) and Methylenetetrahydrofolate redutase-MTHFR (C677T) mutations are the major genetic risk factors for venous thrombosis. This study assessed the frequency of mutations of the Factor V (Leiden), Prothrombin and MTHFR in patients with thrombophilia from the DNA Center Laboratory, Natal - RN. Methods: The detection of mutations was made by PCR-RFLP followed by enzymatic restriction with HindIII (Leiden and Prothrombin) and HinfI (MTHFR). Results: From 69 selected patients, 52 (75.36%) were females and 35 (24.64%) were males. The frequency of genotypes for the Factor V were: 3 mutated homozygous (4.35%), 4 heterozygous (5.80%) and 62 normal homozygous (89.85%). Regarding the mutation in the Prothrombin gene it was observed in 65 normal homozygous patients (94.2%) and 4 (5.8%) heterozygous. The analysis of the mutation in the gene MTHFR showed 35 (50.7%) normal homozygous patients, 5 (7.2%) mutated homozygous patients and 29 heterozygotes patients (42.1%). Conclusions: Approximately 50% of patients tested had at least one type of genetic alteration combined. Based on data obtained it is indicated the investigation of three markers (Factor V, Prothrombin and MTHFR) thrombophilia-related, targeting the real impact of the molecular mutations in thrombosis and the conduct of treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic and predisposing risk factors for perinatal pathology in women with various forms of hyperhomocysteinemia

2012 ◽  
Vol 61 (5) ◽  
pp. 38-42
Author(s):  
Valentina Andreyevna Guryeva ◽  
Yana Mikhaylovna Kostkina
Keyword(s):  
Risk Factors ◽  
Prognostic Significance ◽  
Factor V Leiden ◽  
Factor V ◽  
Perinatal Pathology ◽  
Hemostatic System ◽  
G20210a Mutation ◽  
Factor V Gene ◽  
Prothrombin Gene ◽  
Pai 1

This article shows that folate therapy being carried out since the dispensary registration of women does not prevent the formation of neural tube defects. The determinationof prognostic significance and significance of predisposing risk factors allows predicting the type of hyperhomocysteinemia and its risks. It has been revealed that in case of the congenital form of hyperhomocysteinemia there is a combination with such forms of thrombophilia as the G1691A mutation of the factor V gene (factor V Leiden), the G20210A mutation of the prothrombin gene, PAI-1 gene mutation (5G > 4G). Thus, if congenital hyperhomocysteinemia is diagnosed or may be prognosed, the markers of genetic thrombophiliae should bedetected and the hemostatic system should be investigated. Considering the early formation of defects, the correction, must begin since a pregravid stage, taking into account the detected combinations with changes in the hemostatic system

scholarly journals Predisposition to Thrombophilia and Hypofibrinolysis in Pulmonary Embolism: Analysis of Inherited Factors

2013 ◽  
Vol 6 (2) ◽  
pp. 73-81
Author(s):  
Regina Komsa-Penkova ◽  
Pencho T. Tonchev ◽  
Katya S. Kovacheva ◽  
Galya B. Georgieva ◽  
Yavor Y. Ivanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Gene Mutation ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Platelet Glycoprotein ◽  
Factor V ◽  
Prevention Policy ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Summary Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.

Association between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of PrematurityAssociation between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of Prematurity

2021 ◽  
Author(s):  
Hamideh Shajari ◽  
Mohammadamin Ghadyani ◽  
Seyed Hamed Hosseini-Jangjou ◽  
Reza Bahrami ◽  
Seyed Alireza Dastgheib ◽  
...  
Keyword(s):  
Retinopathy Of Prematurity ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Factor V ◽  
Background Retinopathy ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Rflp Assay ◽  
Preventable Blindness

Background: Retinopathy of prematurity (ROP) is an important cause of preventable blindness in children. The aim of this study was to examine the association of the polymorphisms at Factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene with risk of ROP. Methods: A total of 106 neonates with ROP and 110 healthy neonates were enrolled. The FVL G1691A and MTHFR C677T and A1298C polymorphisms were genotyped by PCR-RFLP assay. Results: There was a significant association between FVL G1691A polymorphism and an increased risk of ROP. However, the MTHFR C677T and A1298C polymorphisms were not associated with risk of ROP. Conclusion: FVL G1691A polymorphism may be risk factor for development of ROP in neonates. However, there was no significant association between MTHFR C677T and A1298C polymorphisms and risk of ROP. However, it is critical that larger and well-designed studies in different ethnicities are needed to confirm our conclusions.

THROMBOPHILIC RISK FACTORS IN PATIENTS WITH CRANIAL AND SPINAL DURAL ARTERIOVENOUS FISTULAE

Neurosurgery ◽  
2008 ◽  
Vol 63 (4) ◽  
pp. 693-699 ◽  
Author(s):  
Rüediger Gerlach ◽  
Martina Boehm-Weigert ◽  
Joachim Berkefeld ◽  
Judith Duis ◽  
Andreas Raabe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Arteriovenous Fistulae ◽  
Factor V Leiden Mutation ◽  
Exact Test ◽  
G20210a Mutation ◽  
Cardiolipin Antibodies ◽  
Prothrombin Gene

ABSTRACT OBJECTIVE Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P < 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

scholarly journals Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5007-5007 ◽  
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Ravitharan Krishnadasan ◽  
Pavani Chalasani ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Dvt Prophylaxis ◽  
Prothrombin Gene ◽  
Baseline Characteristics

Abstract Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Table 1 Summary of baseline characteristics and outcomes. Table 1. Summary of baseline characteristics and outcomes. Disclosures McBride: Sanofi: Research Funding.

scholarly journals Thrombophilia gene mutations in relation to recurrent miscarriage

2018 ◽  
Vol 7 (3) ◽  
pp. 796 ◽  
Author(s):  
Tawfik Abdelsalam ◽  
Tarek Karkour ◽  
Magdy Elbordiny ◽  
Dina Shalaby ◽  
Ziad S. Abouzeid
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Recurrent Miscarriage ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Factor V ◽  
Total Prevalence ◽  
History Of ◽  
Prothrombin Gene

Background: Recurrent pregnancy loss is multifactorial involving clinical and biological risk factors. Evidence addressed the association of inherited thrombophilia with recurrent pregnancy loss and other serious pregnancy complications. However, the relation between thrombophilia associated gene mutations and adverse obstetric outcome is controversial and data in the literature are inconsistent. The aim of this study was to investigate the prevalence of thrombophilia associated gene mutations (factor V Leiden, prothrombin gene G20210A and methylene-tetrahydrofolate reductase MTHFR C677T) in relation to recurrent miscarriage.Methods: Case control study conducted on 200 women recruited from Elshatby Maternity Hospital clinics. The cases group included 100 women with history of three or more unexplained consecutive pregnancy losses, while 100 healthy age matched women with no history of recurrent miscarriages served as controls. Blood samples were collected from all women enrolled in the study for DNA extraction and genotype analysis. Factor V, prothrombin and MTHFR gene mutations were assayed based on polymerase chain reaction (PCR) and reverse-hybridization.Results: The prevalence of Factor V Leiden and prothrombin gene G20210A mutations did not differ significantly between cases and controls. However, MTHFR C667T mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls (p=0.001, p=0.003 respectively). The prevalence of combined thrombophilia of Factor V Leiden and MTHFR C677T was significantly increased in the patients group compared to controls (p=0.032). Regarding homozygosity of each of the gene mutations, no homozygosity was detected in controls and heterozygotes were significantly increased in the patients group compared to homozygotes.Conclusions: MTHFR mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls. There was a significant increase in the prevalence of combined thrombophilia (Factor V Leiden and MTHFR C677T) in the patients group compared to controls without involvement of prothrombin gene.

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