scholarly journals Genetic Mutations Pai-1 4G/4G and ACE D/D that Reduce Fibrinolysis are responsible for most Serious Pregnancy Complications and Abortions and are Best treated with S/C LMW Heparin and Aspirin

2021 ◽  
pp. 01-17
Author(s):  
A. Pierides FRCP ◽  
G. Solomou ◽  
A. Kakoura ◽  
G. Maos ◽  
D. Mavromoustakis ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Factor V Leiden ◽  
Clinical Results ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Healthy Baby ◽  
Positive Factor ◽  
Pai 1 ◽  
In Pregnancy

Background: Abortions, stillbirths, PET and other serious pregnancy complications cause more than 3-4 million pregnancy failures annually worldwide. Hypofibrinolytic and thrombophilia mutations are responsible for a large number of these events. Methods: A study of 11 such genetic mutations (Table 5) in 26 Cypriot ladies after failed pregnancies from serious complications, stillbirths and abortions was carried out between 2006 and 2020. All 26 ladies had significant hypo fibrinolysis and thrombophilia mutations. Hypofibrinolytic mutation PAI-1 4G/4G, was the commonest (X2 p=0.0052) with 11 ladies, 9 of them also ACE D/D positive. Factor V Leiden was present in 5 ladies (X2 p=ns). Clinical results: After the diagnosis of hypo fibrinolysis ± thrombophilia, 19 of these 26 ladies proceeded with 1-2 more pregnancies using LMW s/c heparin and oral aspirin, all with healthy babies. The remaining 7 ladies were too stressed for another pregnancy. 12 ladies were referred after PET, 2 with stillbirths and 9 after caesareans with birthweights at 700, 900, 950, 1050+1080, 1200, 1250, 2050, 2080 and 2200g. One baby developed mental retardation. The 12th lady with PET at 20 weeks, was immediately treated with LMW s/c heparin and had a healthy baby at 32 weeks. The remaining 14 ladies had other earlier pregnancy complications, 9 of them ending as abortions. Three ladies had their pregnancies saved with an instant mutational study and therapy with LMW heparin, leading to healthy babies. Conclusion: Hypofrinolytic mutations PAI-1 4G/4G and ACE D/D are serious mutations leading to abortions and pregnancy complications and should always be taken seriously in pregnancy. Thrombophilia mutations Factor V Leiden, Factor VR2, prothrombin G20210A, and MTHFR also lead to complicated pregnancies but less frequently. LMW s/c heparin in pregnancies with such mutations saves lives. It would be ideal if these mutations were always studied prior to every first pregnancy. Keywords: Mutations PAI-1 4G/4G; ACE D/d In Pregnancy

scholarly journals Evaluation of pai-1 polymorphisms in central and peripheral thromboembolies

2021 ◽  
Vol 38 (2) ◽  
pp. 167-171
Author(s):  
Özge Arıcı DÜZ ◽  
Oktay OLMUŞÇELİK ◽  
Ali İhsan GEMİCİ ◽  
Özlem SAATÇİ SANCAKTEPE
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Vascular System ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Significant Difference ◽  
Medium Risk ◽  
Pai 1

Thromboembolism is a clinical finding that occurs due to thrombus; formed in the vascular system and has various etiological factors. It can be classified as central and peripheral thromboembolism. Our objective in this study is to explore genetic risk factors in central and peripheral thromboembolism and reveal the differences. 342 thromboembolism patients were retrospectively included to the study between January 2016 and December 2019. Demographic characteristics, risk factors for thromboembolism and genetic mutations in central and peripheral thromboembolism groups were overviewed. The genetic mutations evaluated in patients were Factor V Leiden G1691A, Factor V HR1299R, Factor II (Prothrombin) G20210A, MTHFR (Methylenetetrahydrofolate reductase) C677T, MTHFR A1298C, PAI 4G/5G. Within the scope of the study, genetic analyzes of 106 patients were reached and included in the study. Seventy-two central thromboembolism (69.8%), 34 (31.2%) peripheral thromboembolisms were detected. Sixty-three of the central thromboembolisms were from arterial and nine were from venous origin. There was no significant difference between age, gender and risk factors of central thromboembolism and peripheral thromboembolism patients (p˃0.05), but smoking was more common in central thromboembolism patients (p: 0.041). 4G/5G polymorphism was observed more frequently in patients with central thromboembolism (p: 0.039). Thromboembolism is a multifactorial disease, PAI-1 4G/5G polymorphism is a medium risk factor for thromboembolism. We conclude that PAI-1 4G/5G polymorphism is more frequent in central thromboembolism than peripheral thromboembolism and its evaluation can give more information about the thromboembolic risk analyze.

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 >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 >80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p<0.001. Conclusion Previous results of our work indicate influence of waist circumference >80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference >80 cm. FUNDunding Acknowledgement Type of funding sources: None.

Acute coronary syndrome and thrombophilia in young patients:clinical data, experience

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Stoykova ◽  
V Dimitrova ◽  
I Tasheva ◽  
L Dosev ◽  
N Zlatareva-Gronkova ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Family History ◽  
Treatment Algorithm ◽  
Young Patients ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Coronary Syndrome ◽  
Pai 1

Abstract Introduction There is an increasing number of young patients with acute coronary syndromes. The gold standard for diagnosis and treatment remains coronary angiography and primary percutaneous coronary intervention (PPCI). Especially in young individuals there are cases with large thrombus burden and almost none angiographically visible coronary atherosclerosis, which raises major concerns about the etiological cause for such events. Thrombophilia can lead to repeated and unexplained thrombus formation and that is why recently there is an increasing interest in the relationship between thrombophilia and acute coronary syndrome (ACS) in early age. Still there's no precise treatment algorithm. Purpose To diagnose and evaluate the frequency of thrombophilia in patients presenting with first ACS in young age and to alter future treatment in order to prevent further events and improve prognosis. Methods We evaluated all patients with first ACS from age<40 for men and women <50 in our hospital for 3 years. All patients were diagnosed and treated with PPCI. Complete family history was taken. We performed laboratory tests for the most frequent gene mutations, responsible for thrombophilia factor V Leiden, PAI –1 4G/5G, prothrombin G20210A, MTHFR - C677T, MTHFR A 1287C, MTHFR A 1298C and glycoprotein IIb/IIIa in all patients. Results 210 patients with ACS were admitted with 36 young patients (age men <40 and women <50). In all we performed screening for thrombophilia. 32 individuals (5 women and 27 men; mean age of 46) had a distinct genetic variation which can be attributed to thrombophilia. 85% of them had family history for ischemic heart disease. The conventional risk factors for coronary artery disease (CAD), including arterial hypertension, dyslipidemia, smoking, and diabetes were presented respectively in 43%, 57%, 43% and 3% in the group. The most often diseased artery was the left anterior descending artery (LAD). The genetic evaluation results were 20% homozygotes of pathogenic variation of factor V of Leiden, 7% heterozygotes of pathogenic form of factor V of Leiden 25% PAI 1 4G/5G homozygotes, 11% PAI 1 4G/5G heterozygotes, 13% prothrombin G20210A homozygotes and 2% prothrombin G20210A heterozygote. In 28% the index event was a repeated ACS and 4% has had a previous ischemic stroke. We then consulted all of them with haemathologist and altered further discharge treatment (in 100% new oral anticoagulants (NOAC) was added to dual antipatled therapy). In follow up at the first year 70% were left on aspirin 100mg and NOAC and 10% were considered high risk and were left on two NOAC. Conclusion Thrombophilia is an indipendant risk factor for myocardial infarction in young patients and should not be easily overlooked. In them screening for thrombophilia could be beneficial, especially for the follow-up treatment and improvement of the late prognosis. Such detection could prevent subsequent AMI. Funding Acknowledgement Type of funding source: Private hospital(s)

Clotting Factor Gene Polymorphisms and Colorectal Cancer Risk

2011 ◽  
Vol 29 (13) ◽  
pp. 1722-1727 ◽  
Author(s):  
Carla Y. Vossen ◽  
Michael Hoffmeister ◽  
Jenny C. Chang-Claude ◽  
Frits R. Rosendaal ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Gene Polymorphisms ◽  
Factor V Leiden ◽  
Colorectal Cancer Risk ◽  
Clotting Factor ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor Gene ◽  
Pai 1

PurposeIncreased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study.Patients and MethodsFactor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression.ResultsHomozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk.ConclusionOur results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.

Aetiology of pre-eclampsia and thrombophilic genetic mutations

2003 ◽  
Vol 105 (3) ◽  
pp. 269-271 ◽  
Author(s):  
M. HAYASHI
Keyword(s):  
Gene Mutation ◽  
Intrauterine Growth Restriction ◽  
Hellp Syndrome ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Intrauterine Growth ◽  
Cytokine Imbalance ◽  
Thrombophilic Mutations

Schlembach and co-workers in this issue of Clinical Science have studied the association of maternal and/or fetal factor V Leiden (FVL) and prothrombin G20210A gene mutation with HELLP syndrome and intrauterine growth restriction (IUGR) to confirm whether these genetic mutations are important risk factors for the pathogenesis of the HELLP syndrome, leading to an inadequate maternal–fetal circulation. Results showed that fetal FVL and prothrombin G20210A gene mutation were significantly associated with IUGR. The authors speculated that fetal thrombophilic mutations resulted in placental microthrombosis, leading to a disturbed fetoplacental blood flow. This study represents another important step in our understanding of the pathophysiological action of fetal thrombophilic mutations on fetal development. Regarding the aetiology of pre-eclampsia, one possible speculation is that systemic immune maladaptation, including systemic cytokine imbalance, contributes to placental ischaemia and systemic vessel abnormalities leading to pre-eclampsia.

Association of increased C-Reactive Protein and hypocomplementemia with risk factors for thrombosis in women who have susceptibility for poor gestational outcome; importance of preconceptional counseling

2021 ◽  
pp. 1-6
Author(s):  
Mehmet Sinan Beksac ◽  
Hanife Guler Donmez
Keyword(s):  
Risk Factors ◽  
Inflammatory Diseases ◽  
Factor V Leiden ◽  
Care Program ◽  
Prothrombin G20210a ◽  
Study Group ◽  
Factor V ◽  
C Reactive Protein ◽  
Mthfr Polymorphisms ◽  
Reactive Protein

This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n= 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n= 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n= 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p= 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p= 0.386, p= 0.462, p= 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications.

Thromboembolism in heart transplantation: Role of prothrombin G20210A and factor V Leiden

2005 ◽  
Vol 24 (2) ◽  
pp. S123
Author(s):  
S.G. Miriuka ◽  
L.J. Langman ◽  
J. Evrovski ◽  
S.E. Miner ◽  
S. Kozuszko ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V
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