Prothrombin 20210G Research Articles

Impact of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210 A mutations on the development of neonatal thrombosis

Impact of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210 A mutations on the development of neonatal thrombosis

He Asossiation Of Prothrombin G20210 Gene Polymorphism And Risk of Thrombosis in B.Thalassemic Children in Egypt

he Asossiation Of Prothrombin G20210 Gene Polymorphism And Risk of Thrombosis in B.Thalassemic Children in Egypt

Recommendations from the EGAPP Working Group: Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members

Summary of RecommendationsThe Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found adequate evidence to recommend against routine testing for Factor V Leiden (FVL) and/or prothrombin 20210G>A (PT) in the following circumstances: (1) adults with idiopathic venous thromboembolism (VTE). In such cases, longer term secondary prophylaxis to avoid recurrence offers similar benefits to patients with and without one or more of these mutations. (2) Asymptomatic adult family members of patients with VTE and an FVL or PT mutation, for the purpose of considering primary prophylactic anticoagulation. Potential benefits are unlikely to exceed potential harms. The overall certainty of these findings was deemed “moderate.” The evidence was insufficient to determine whether FVL/PT testing might have clinical utility in some circumstances, such as for identifying FVL homozygosity among asymptomatic family members of adults with idiopathic VTE or counseling patients about the risks and benefits of antithrombotic therapy. Based on the available evidence, the certainty of net health benefit was deemed “low.” The recommendations do not extend to patients with other risk factors for thrombosis, such as contraceptive use, as the evidence review that serves as the basis for the recommendations focused primarily on idiopathic VTE. RationaleIn developing these recommendations the EGAPP Working Group considered evidence in the following three areas. Analytic ValidityThere is adequate evidence that testing accurately and reliably detects the R506Q (FVL) and 20210G>A (PT) variants in the Factor V and PT genes, respectively (a more complete definition of analytic validity, clinical validity, and clinical utility is contained under the “Clinical Considerations” section). Clinical ValidityThe presence of a heterozygous FVL variant seems to be a weak risk factor for recurrence of VTE (odds ratio [OR]: 1.56). Rare homozygous FVL mutations present somewhat greater risks of VTE recurrence (OR: 2.65). The evidence for this increased risk is convincing, but the magnitude of excess risk is not as great as previously thought. The evidence is insufficient to draw conclusions about excess VTE recurrence risk resulting from compound heterozygosity (FVL and PT), but it is likely to be at least as high as with FVL alone. The OR for compound heterozygosity is 6.69. The evidence is insufficient to draw conclusions about VTE recurrence risks associated with PT mutations alone. For family members of index VTE cases, there is convincing evidence that both heterozygosity and homozygosity for FVL are associated with higher risks for VTE occurrence (ORs 3.49 and 17.84, respectively) than for family members without FVL variants. Clinical UtilityThere is convincing evidence that longer term secondary prophylaxis after an initial idiopathic VTE event yields comparable benefits to those with and without a FVL or PT mutation. For asymptomatic family members of index cases, no prophylaxis trials have been reported. Hence, there is no direct evidence of particular benefit to family members. Potential net harm is possible if primary prophylaxis is administered to asymptomatic family members with one or more mutations, because the absolute risk of an initial VTE event is low, and the risk of anticoagulant-induced hemorrhage is relatively high.

Hypercoagulability in patients with indirect carotid cavernous fistulas.

To assess patients with indirect carotid-cavernous fistulas (CCF) for evidence of hypercoagulable state (HS) by combination of comprehensive medical questionnaire and laboratory testing. Patients with confirmed diagnosis of CCF treated between 2003 and 2019 were included and administered a questionnaire screening for HS risk factors and undergone laboratory investigations which included complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody titres), Factor V Leiden, prothrombin, protein C, protein S, antithrombin III, homocysteine, prothrombin G20210, CALR and JAK2 mutation screening. Participants with abnormal laboratory testing and/or past history of ischemic stroke, atrial fibrillation, cancer or hypercoagulability-associated hereditary disorders were deemed to have HS. Twenty-two patients were enrolled. Seventeen were women and the mean age at diagnosis was 60. Fourteen (64%) had evidence of HS: six on medical history, three with laboratory evidence and five with both. Eight (36%) had current abnormal hypercoagulability markers. One had a diagnosis of Klippel-Trenaunay Syndrome, but no others had evidence of hereditary thrombophilia. Nine were on anti-coagulation initiated after diagnosis of stroke or atrial fibrillation discovered on average 5.5 years after the diagnosis of CCF. A total of 64% percent of patients with previous indirect CCF had evidence of underlying HS indicating that hypercoagulability might play a role in the pathogenesis of CCF. The results support need for comprehensive testing for underlying HS in patients with indirect CCFs to better identify, manage, and prevent further thromboembolic events.

Direct-to-consumer genetic testing for factor V Leiden and prothrombin 20210G>A: the consumer experience.

BackgroundClinical genetic testing for inherited predisposition to venous thromboembolism (VTE) is common among patients and their families. However, there is incomplete consensus about which individuals should receive testing, and the relative risks and benefits.MethodsWe assessed outcomes of receiving direct‐to‐consumer (DTC) results for the two most common genetic risk factors for VTE, factor V Leiden in the F5 gene (FVL) and prothrombin 20210G>A in the F2 gene (PT). Two thousand three hundred fifty‐four customers (1244 variant‐positive and 1110 variant‐negative individuals) of the personal genetics company 23andMe, Inc., who had received results online for F5 and F2 variants, participated in an online survey‐based study. Participants responded to questions about perception of VTE risk, discussion of results with healthcare providers (HCPs) and recommendations received, actions taken to control risk, emotional responses to receiving risk results, and perceived value of the information.ResultsMost participants (90% of variant‐positive individuals, 99% of variant‐negative individuals) had not previously been tested for F5 and/or F2 variants. The majority of variant‐positive individuals correctly perceived that they were at higher than average risk for developing VTE. These individuals reported moderate rates of discussing results with HCPs (41%); receiving prevention advice from HCPs (31%), and making behavioral changes to control risk (e.g., exercising more, 30%). A minority (36%) of variant‐positive individuals worried more after receiving VTE results. Nevertheless, most participants reported that knowing their risk had been an advantage (78% variant‐positive and 58% variant‐negative) and were satisfied knowing their genetic probability for VTE (81% variant‐positive and 67% variant‐negative).ConclusionConsumers reported moderate rates of behavioral change and perceived personal benefit from receiving DTC genetic results for VTE risk.

Association of Prothrombin G20210A Mutation with Unexplained Recurrent Pregnancy Loss

Purpose: To assess the relationship of Prothrombin G20210A gene mutations as a risk factor for idiopathic repeated pregnancy loss. The focus has been on Prothrombin G20210 Amutation that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Method: A total of 70 women with recurrent pregnancy loss, mean age 31.1±4.2 years, were involved in the study. As a control group, 70 women [mean age 32.2±3.3y ears with at least two live-born child and no history of abortion were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of Prothrombin G20210 Agenotype. Results: The frequency of heterozygotes for F2 was significantly higher in women with repeated pregnancy loss compared to women without abortion (p = 0.0001). Conclusion: In summary we found an association of prothrombin G20210A mutation with recurrent pregnancy loss .we recommend for prothrombin G20210A screening in cases with repeated pregnancy loss so they can start anticoagulant therapy more earlier

Increased Activated Protein C Response Rates Reduce the Thrombotic Risk of Factor V Leiden Carriers But Not of Prothrombin 20210G>A Carriers.

Carriers of the most common prothrombotic mutations FVL (factor V Leiden) and FII (prothrombin) 20210G>A show a highly variable clinical phenotype. Using standardized in vivo coagulation activation followed by activity pattern analysis we have recently shown, that the FVL mutation accelerates thrombin and APC (activated protein C) formation in carriers without a history of venous thromboembolism (VTE). The aim of this prospective cohort study was to investigate, if the FII 20210G>A mutation induces a similar reaction pattern, and if the response rates differ in FVL and FII 20210G>A mutation carriers with prior VTE (VTE+). We comparatively analyzed 30 FVL carriers, 28 FII 20210G>A carriers (thereof 13 VTE+ each) and 15 healthy controls. Changes in plasma levels of thrombin, prothrombin activation fragment 1+2 (F1+2), TAT (thrombin-antithrombin complex), APC, and D-dimer were monitored over 8 hours after infusion of recombinant factor VIIa (15 µg/kg). An increase of F1+2 and TAT levels was observed, that did neither differ between FVL and FII 20210G>A carriers nor between asymptomatic and VTE+ carriers of these mutations. Median plasma levels of APC increased more (P=0.008) in FVL carriers (from 1.39 to 7.79 pmol/L) than in FII 20210G>A carriers (from 1.03 to 5.79 pmol/L), and more in FII 20210G>A carriers (P=2×10-4) than in healthy controls (from 0.86 to 3.00 pmol/L). Most importantly, however, the APC response was greater (P=0.015) in asymptomatic (n=13) than in VTE+ (n=12) heterozygous FVL carriers, with an increase of APC levels from 1.44 to 8.11 pmol/L versus 1.27 to 5.62 pmol/L. These in vivo data demonstrate that the FII 20210G>A and FVL mutations share an intermediate phenotype that is characterized by increased thrombin formation after coagulation activation. Furthermore, our data support the conclusion that the APC activating capacity of FVL carriers modifies the thrombotic risk of this common prothrombotic mutation.

Thrombophilic gene polymorphisms are associated with deep venous thrombosis in a cohort of Egyptian patients

Background There is several evidence suggesting, that inherited thrombophilia increases the susceptibility to venous thromboembolism (VTE). Aim is to detect prothrombotic genes polymorphisms possible association with the risk of occurrence of venous thrombosis. Methods A group of eleven gene polymorphisms related to the risk of thromboembolic events were studied; including Factor V Leiden(FVL) 1691G>A, Methylene tetrahydrofolate reductase gene (MTHFR) C677>T and others. Genotyping was done using PCR, and identification of corresponding bands using the StripAssay in 493 patients with clinical symptoms of deep venous thrombosis (DVT). Five hundred age and sex matched healthy individuals were included as a control group. Results Genotyping of DVT patients showed significantly higher prevalence of FVL 1691G>A, MTHFR C677>T, MTHFR 1298A>C, Prothrombin 20210G>A, PAI 4G, FVIII V34L, B Fibrinogen 455G>A, HPA-1, ACE and APO E e4 gene polymorphisms (p Conclusion Individuals carrying thrombophilic genes polymorphisms are at a greater risk for venous thrombosis.

Ферментный тромболизис и «массаж» при окклюзии вен сетчатки

Введение. На сегодняшний день некоторые аспекты возникновения тромбоза ретинальных вен остаются дискутабельными. Большое количество факторов развития заболевания, отсутствие единой концепции патогенеза обтурации вен сетчатки приводят к неопределенности в тактике ведения пациентов, что снижает качество лечения. Цель исследования: проанализировать состояние микроциркуляции при окклюзии ретинальных вен на фоне применения «массажа» пораженной вены сетчатки и эпиретинального введения ферментного тромболитика. Материалы и методы. Обследовано 96 человек (49% мужчин и 51% женщин в возрасте 60,2 ± 1,9 года) с обтурацией ретинальных вен. Пациентам основной группы (n = 47) выполняли «массаж» пораженной вены сетчатки и эпиретинальное введение 500 МЕ рекомбинантной проурокиназы; пациентам группы сравнения (n = 49) однократно вводили эпиретинально 500 МЕ рекомбинантной проурокиназы на фоне традиционной фармакотерапии. Результаты. Индукция тромболизиса при помощи «массажа» пораженной вены сетчатки на фоне эпиретинального введения ферментного фибринолитика в 2 раза ускоряла восстановление кровотока в ретинальном сосуде и в 1,5 раза сокращала время резорбции отека центральных отделов сетчатки, обеспечивая эффективное (в 1,7 раза) повышение биоэлектрической ретинальной активности. Заключение. «Массаж» ретинальных вен на фоне ферментного тромболизиса, проведенный в первые 7 дней от начала заболевания, является перспективным методом лечения окклюзии вен сетчатки. Introduction. Currently some aspects of retinal vein thrombosis remain controversial. A large number of disease development factors, absence of unifi ed pathogenesis conception for retinal veins obturation lead to non-specifi city in tactics of patient management that reduces the quality of treatment. Aim: to analyze microcirculation in retinal veins occlusion under the «massage» of the aff ected retinal vein and epiretinal administration of thrombolytic enzyme. Materials and methods. We examined 96 people (49% of men and 51% of women aged 60.2 ± 1.9 years) with obturation of retinal veins. Patients of the main group (n = 47) were treated by «massage» of the aff ected retinal vein and epiretinal administration of recombinant prourokinase (500 IU); patients of the comparison group (n = 47) were treated by traditional pharmacotherapy with single epiretinal injection of recombinant prourokinase (500 IU). Results. Thrombolysis induction using the «massage» of aff ected retinal vein with epiretinal administration of thrombolytic enzyme accelerated the restoration of blood fl ow in retinal vessel in 2 times and in 1.5 times reduced the resorption time of edema in central retina parts that provided an effective (1.7 times) increasing of bioelectric retinal activity. Conclusion. «Massage» of retinal vein occlusion with enzymatic thrombolysis conducted in first 7 days from disease onset is a promising method for treatment of retinal vein occlusion.

Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation

ObjectiveMaternal thrombophilia is a risk factor for adverse pregnancy outcomes. The aim of this study was to elucidate the controversial role of fetal and paternal thrombophilia in the development of severe placenta-mediated pregnancy complications. Study DesignThe study group comprised 126 mothers, 72 fetuses and 58 fathers. 111 mothers, 50 fetuses and 91 fathers acted as controls. 106 couples were selected to study the thrombophilias of paternal inheritance, 58 from the study group and 48 from the control group. The prevalence of factor V Leiden mutation, prothrombin G20210 A mutation and homozygous 10-methylenetetrahydrofolate reductase C677 T mutations were compared between the study and control groups to study whether maternal, fetal or paternal thrombophilias increase the risk of severe preeclampsia, intrauterine growth restriction, placental abruption and stillbirth. ResultsThe total prevalence of fetal thrombophilic mutations was 8.3% in the study group and 14.0% in the control group. Paternal prevalence of thrombophilic mutations was 6.8% and 4.3%, respectively. There were no statistical differences between fetal or paternal thrombophilic mutations between the study and control groups. ConclusionFetal or paternal factor V Leiden mutation is not associated with severe placenta-mediated pregnancy complications.

Comparison of two groups for the apolipoprotein E polymorphisms by using next generation sequencing: The first group with three consecutive abortions and the second group with at most one abortion in three consecutive pregnancies

The importance of apolipoprotein E genotypes and allelic polymorphisms in the etiology of recurrent miscarriage is controversial. We plan to investigate this in a two-group study involving more than a thousand participants. In total, 1046 subjects (802 participants in the first group, 244 participants in the second group) were investigated. Women in the first group had a history of ≥3 consecutive spontaneous miscarriage and women in the second group had at most one miscarriage in three consecutive pregnancies. The participants with the following evidence and symptoms were excluded from both groups; structural uterine abnormality, chrosomal abnormalities and polymorphisms, hormonal imbalance, anti-nuclear antibodies, anti-phospholipid antibodies, lupus anticoagulant and homozygous genotype for FV-Leiden, MTHFR C677T, MTHFR A1298C, prothrombin 20210G>A and plasminogen activator inhibitor 4G/5G polymorphisms. We found similar apolipoprotein E allelic frequencies and genotype distributions in both groups. The frequencies of ε2 alleles were 4.1% in the first group and 2.9% in the second group, whereas those of ε3 alleles were 90.8% and 93% in the first group and the second group, respectively and ε4 alleles were 5.1% in the first group and 4.1% in the second group. The genotypes of Apo E observed in the first and the second group respectively were as follows; ε2/ε3 (7.5% and 5.7%), ε3/ε3 (82.7% and 86.5%), ε3/ε4 (8.7% and 7.4%), ε4/ε4 (0.5% and 0.4%) and ε2/ε4 (0.6% and 0). Our data did not support a possible association between apolipoprotein E genotypes and allelic frequencies, and recurrent miscarriages. We believe that the studies excluding the etiological factors that were previously found to be related with any condition are more valuable in the scope of showing the cause–effect relationship.

The Role of Factor V Leiden 1691G>A and Prothrombin Gene 20210G>A Mutations in Hypercoagulable State Associated with Venous Thromboembolism among Sudanese Patients

Background: Factor V Leiden (FVL) 1691G>A and Prothrombin (PRT) 20210G>A mutations are the most frequent hereditary cause of venous thrombosis in Caucasian and less frequency in African. The aim of this study was to detect the frequency of FVL 1691G>A and PRT 20210G>A mutations among Sudanese venous thromboembolism (VTE) patients. Material and Methods: This was descriptive Cross sectional study in which a total of 176 Sudanese subjects were enrolled in the period between July 2015 and July 2016. Among them, 38 apparently healthy Sudanese individuals as controls and 138 patients (47 males and 91 females), age range 18-90 with documented VTE confirmed by Duplex Doppler ultrasound at Khartoum Teaching Hospital and Sudan Heart Institute were included. Result: In this study, the mean age was 48 years and 67% of total VTE patients were over the age of 40 years. Increased age was noted in the VTE patients with over 34% over the age of 60 years. The controlled subjects included significantly younger individual with 92.1% under the age of 50 and 81.5% under the age of 40 years. The FVL 1691G>A and PRT 20210G>A mutations were totally absent among the studied population. Conclusion: The FVL 1619G>A and PRT 20210G>A mutations were totally absent among Sudanese VTE patients.

Alterations in Platelet Activity and Elastic Modulus of Healthy Subjects, Carriers of G20210A Polymorphism in the Prothrombin Gene

Summary Platelet activation is a complex process in which platelet reorganization takes place associated with changes in the cell shape, topology, membrane elasticity and microparticle production. The aim of this study was to investigate the changes/aberrations in the platelet activity, elasticity and morphology in healthy subjects, carriers of A allele of prothrombin G20210A polymorphism. Blood samples from 18 healthy subjects were used for platelet analysis by force-mode atomic force microscopy. Restriction analysis was used to investigate the carriage of G20210A polymorphism in the prothrombin gene. Flow- cytometry was applied to evaluate platelet activation. Young’s modulus of the plasma membranes of platelets derived from healthy subjects, carriers of variant A allele of prothrombin 20210G>A polymorphism (407±69 kPa) is two times higher than the one determined for non­carriers (195.4±48.7 kPa; p<0.05). The background activity of platelets measured as an interrelation of Cd41/Cd61 and CD62 by flow cytometry was also higher in carriers of variant A allele of prothrombin 20210G>A polymorphism (5.0%) than in non-carriers (1.3%). Platelets isolated from healthy carriers of variant A allele of prothrombin 20210G>A polymorphism exhibited a higher level of activity and a higher degree of stiffness at the stage of spreading as compared to platelets from non­carriers.

Multigenic forms of thrombophilia in habitual miscarige.

Miscarriage is an actual problem of modern obstetrics. The frequency of miscarriage is 10-25% of all pregnancies, and habitual abortion occurs in 5%. Habitual miscarriage is considered as a typical multifactorial disease, being the result of expression of functionally weakened versions of many genes on the background of adverse external and internal factors. The genetic nature of habitual miscarriage includes groups of genes responsible for hemostatic disorders and endothelial dysfunction. The aim of the study was to determine the frequency and the role of combination of allelic variants of thrombophilia genes and endothelial dysfunction in the development of habitual miscarriage. 109 women with recurrent miscarriage and 34 apparently healthy pregnant women were tested with allele specific polymerase chain reaction and genetic polymorphisms of coagulation factors and fibrinolysis (1691 G → A factor V Leiden, 20210 G → A prothrombin, 5G/4G PAI-1, -455 G → A fibrinogen β) and endothelial dysfunction (192 Q → R PON-1, 677 C → T MTHFR) were identified. The study showed the expediency of examination of women with habitual miscarriage for the presence of an inherited defect in the hemostatic system (gene mutations factor V Leiden, prothrombin 20210G → A, polymorphism of PAI-1 5G / 4G, fibrinogen β -455 G → A) and endothelial dysfunction (MTHFR gene polymorphism 677 C → T). A high frequency of multigene form of thrombophilia (two or more defects) in patients with habitual miscarriage - 80.7% was detected. Pathologic polymorphisms that cause fibrinolysis defects in combination with dysfibrinogenemia were identified the most frequently.

PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis.

To evaluate the different roles of thrombophilia in patients with and without viral etiology. The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and prothrombin 20210A, were studied as risk factors in 1079 patients with liver cirrhosis (LC), enrolled from January 2000 to January 2014. All Caucasian LC patients consecutively observed in a fourteen-year period were included; the presence of portal vein thrombosis (PVT) and Budd Chiari syndrome (BCS) was registered. The differences between the proportions of each THRGF with regard to the presence or absence of viral etiology and the frequencies of the THRGF genotypes with those predicted in a population by the Hardy-Weinberg equilibrium were registered. Four hundred and seventeen/one thousand and seventy-six patients (38.6%) showed thrombophilia: 217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leiden factor and 41 prothrombin G20210 A, 84 with more than 1 THRGF; 350 presented with no viral liver cirrhosis (NVLC) and 729 with, called viral liver cirrhosis (VLC), of whom 56 patients were hepatitis C virus + hepatitis B virus. PAI-1 4G-4G, MTHFR C677TT, the presence of at least one TRHGF and the presence of > 1 THRGF, were statistically more frequent in patients with NVLC vs patients with VLC: All χ (2) > 3.85 and P < 0.05. Patients with PVT and/or BCS with at least one TRHGF were 189/352 (53.7%). The Hardy-Weinberg of PAI-1 and MTHFR 677 genotypes deviated from that expected from a population in equilibrium in patients with NVLC (respectively χ (2) = 39.3; P < 0.000 and χ (2) = 27.94; P < 0.05), whereas the equilibrium was respected in VLC. MTHFR 677TT was nearly twofold and PAI-1 4G-4G more than threefold more frequently found in NVLC vs patients with VLC; the Hardy-Weinberg equilibrium of these two polymorphisms confirms this data in NVLC. We suggest that PAI-1 4G-4G and MTHFR 677TT could be considered as factors of fibrosis and thrombosis mechanisms, increasing the inflammation response, and causing the hepatic fibrosis and augmented intrahepatic vascular resistance typical of LC. PAI-1 4G-4G and MTHFR 677TT screening of LC patients could be useful, mainly in those with NVLC, to identify patients in which new drug therapies based on the attenuation of the hepatic stellate cells activation or other mechanisms could be more easily evaluated.

The Prevalence of the Prothrombin (F2) 20210G>A Mutation in a Cohort of Sri Lankan Patients with Thromboembolic Disorders.

Prothrombin (F2) 20210G>A [rs1799963 G>A] mutation is a genetic variant which predisposes to inherited thrombophilia. Highest prevalence of this rare mutation has been reported among Caucasian and Mediterranean populations with thrombophilic conditions compared to healthy controls. It is absent or occurs in a very low frequency in both thrombophilic patients and healthy controls of most South Asian populations. A previous study has demonstrated that the mutant allele is absent among Sri Lankan healthy controls. This study was conducted to determine the prevalence of the F2 20210G>A mutation among Sri Lankan patients with thrombo-embolic disorders. F2 20210G>A mutation analysis was carried out on 825 patients. These included 374 with arterial thromboembolic disorders, 303 with venous thromboembolic disorders (VTE) and 148 with pregnancy related complications. Genotyping was done using polymerase chain reaction followed by restriction fragment length polymorphism. The overall prevalence of the individuals detected with the mutation was 0.8% (7/825) with a mutant allele frequency of 0.4% (7/1,650), and all were heterozygotes. Further classification according to the types of thrombotic events showed a prevalence of 0.5% (2/374), 1.3% (4/303), and 0.7% (1/148) respectively, in the three groups with arterial thrombosis, VTE and pregnancy complications. The respective mutant allele frequencies in the three different groups were 0.3% (2/748), 0.7% (4/606) and 0.3% (1/296). Although these figures are lower than that of Caucasian and Mediterranean populations, they are relatively higher compared to other South Asian populations. Therefore, the F2 20210G>A mutant allele is not entirely absent among Sri Lankan patients with thrombo-embolic disorders.

A deep vein thrombosis caused by 20209C&gt;T mutation in homozygosis of the prothrombin gene in a Caucasian patient

Introduction:Additional nucleotide substitutions in the 3′-untranslated region of prothrombin gene could explain some thrombotic events and also adverse pregnancy outcomes. We describe the first case of a homozygous 20209C>T mutation as the cause of deep vein thrombosis in a Spanish patient.Case and methods:The 56-year-old male patient with a partial tear of the Achilles tendon developed calf (tibial) deep vein thrombosis after immobilization and was treated with an anticoagulant. To determine if the deep vein thrombosis was of genetic origin, a peripheral blood DNA sample was analysed for the presence of the three most frequent mutations associated with thrombotic events: factor V Leiden (1691G>A), prothrombin (20210G>A) and methylene tetrahydrofolate reductase (677C>T). The presence or absence of the normal allele of prothrombin could not be determined using the PTH-FV-MTHFR StripAssay (Vienna Lab).Results:Comprehensive analysis showed that the patient had a variant interfering with the polymerase chain reaction product, we sequenced the entire prothrombin gene and found that the patient had a homozygous C>T mutation at position 20209; this interfered with the polymerase chain reaction product, which needs a C at this position to be able to bind to the wild-type probe present in the test strip.Conclusion:The homozygous 20209C>T mutation and the presence of the mutation 677C>T in heterozygosity explained the patient’s deep vein thrombosis because the combination of mutations would increase the risk of thrombosis. Suitable genetic counselling should be provided to the patient and first-degree relatives as it important to detect prothrombin gene variants that could increase risk for thrombotic events.

A Restrospective Review Of Thrombophilia Evaluation At a Single Academic Institution

There is no consensus exists regarding which patients should be evaluated for thrombophilia. Also there is no clear role for hypercoagulobility screening (HS) in patients with unprovoked thrombosis. However if decision to test is made there are disorders that may significantly increase the risk for recurrent thrombosis. An important application of this knowledge is a possible change in the length of anticoagulation. Nevertheless reports from investigators in Europe indicated that few institutions adhere to evidence based testing. We conducted a retrospective review of tests used in our institution by different services to investigate for hypercoagulobility in 100 consecutive patients with acute pulmonary embolism (PE) between 2008 and 2012. Age, provoking factors and recurrence, thrombophilia tests and its timing in respect to acute thrombosis and anticoagulation were reviewed. The source of data was an electronic medical record system used by all providers in our institution. Of 100 cases 50 had provoking factors and 30 of them had HS. Of 50 patients with unprovoked PE 16 had no HS and 2 of them had recurrent PE. There was no consistent pattern in ordering HS, neither in regards of time from acute thrombosis nor panel components. 26 patients had protein C and S testing and 28 had antithrombin (AT) done at the time of the diagnosis of an acute PE. In nearly all cases these tests were not repeated later. While screening for antiphospholipid antibodies syndrome (APLAS) 34 patients were tested for lupus anticoagulant, 32 for anticardiolipin antibodies (ACA) and 24 for anti-beta2-glycoprotein antibodies. Only 12 patients had tests for all three groups of antiphospholipid antibodies. Notably all patients tested for ACA had IgM, IgG and IgA measured, even though IgA is not included in Sapporo criteria. In 2 cases when one of these antibodies was positive the test was not repeated 12 weeks later. Regarding common inherited thrombophilias 52 patients underwent both factor V Leiden and prothrombin G20210 mutations screens. Only 20 of them had prior evaluation for activated protein C resistance. The least relevant tests, such as homocysteine level, PAI-1, factor VIII and vWF were performed in 24, 4, 14 and 4 cases, respectively. Interestingly, out of 18 patients tested for MTHFR mutations only 12 had prior homocysteine measurement and 4 cases were reflected to MTHFR screening with normal homocysteine level. In conclusion our review revealed significant variability in HS that appeared to be greater if tests were ordered by non hematology providers. Although there are no universally accepted guidelines for HS most high risk thrombophilias are well recognized and should be screened for appropriately. Our results are similar to those reported by investigators in Europe. The problem of HS variability and poor efficacy will persist as long as guidelines are not available. Our institution is planning to improve quality of service by creating a battery of tests that will be available to all services when decision to screen is made. Disclosures: No relevant conflicts of interest to declare.

Isolated Cortical Vein Thrombosis Associated with Prothrombin Gene Mutation

Isolated cortical vein thrombosis (ICVT) accounts for less than 1% of strokes. We report a 47-year-old female patient who had a frontal hemorrhage with headache associated with contralateral hemiparesis and hemisensory deficit on presentation. This hemorrhagic stroke was localized in a nonarterial territory, and it was caused by ipsilateral and isolated thrombosis of the vein of Labbe found on catheter angiogram that demonstrated a filling defect of the vein of Labbe at its connection with the transverse sinus. There were no filling defects in the superficial middle cerebral veins. Our patient had a family history of cardiovascular disease, stroke, and factor V Leiden mutation and cigarette smoking as stroke risk factors. Complete prothrombotic state laboratory workup revealed a heterozygous prothrombin G20210 A gene mutation. The patient's hospital course was uneventful. Neurologic exam was normal at stroke clinic follow-up 6 weeks later. To our knowledge, this is the first report of an ICVT associated with prothrombin gene mutation.

Hemodialysis duration, Human platelet antigen HPA-3 and IgA Isotype of anti-β2glycoprotein I antibodies are associated with native arteriovenous fistula failure in Tunisian hemodialysis patients

IntroductionArteriovenous fistula (AVF) failure is a major cause of morbidity and mortality in hemodialysis patients. We assessed the role of a large panel of acquired and inherited thrombophilic markers in cases of AVF thrombosis among 101 Tunisians on chronic hemodialysis, all with native AVF. Materials and MethodsIn this case-control study, we considered the levels of fibrinogen, factor II, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, von Willebrand factor, natural coagulation inhibitors, D-Dimer, homocysteine, IgG, IgM and IgA anticardiolipin and anti-β2glycoprotein I (anti-β2GPI), and anti-H/PF4 antibodies; the presence of Lupus Anticoagulant; and genetic markers (Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C). ResultsMultivariate analysis indicated that dialysis for >69months (OR=10.12; 95% CI, 2.53 to 40.52; p=0.001), HPA-3aa genotype (OR=3.58; 95% CI, 1.36 to 9.4; p=0.01) and anti-β2GPI IgA isotype (OR=3.4; 95% CI, 1.21 to 9.55; p=0.02) were independent risk factors for AVF thrombosis in Tunisian hemodialysis patients. Kaplan-Meier analysis showed that AVF survival was significantly lower for patients with anti-β2GPI IgA than for patients without this isotype (log-rank test, p=0.014). ConclusionsIgA anti-β2GPI may be of clinical relevance among Tunisians. Further studies on the polymorphism of β2GPI and HPA systems would be helpful for identifying patient groups at high risk of AVF failure.