Factor V Leiden Research Articles

Prothrombotic genetic risk factors in patients with very early ST-segment elevation myocardial infarction

The contribution of prothrombotic genetic risk factors in the pathogenesis of premature acute myocardial infarction (MI) is controversial. We examined the prevalence of prothrombotic polymorphisms (G1691A of factor V gene [FV Leiden] and G20210A of prothrombin [FII] gene), deficiencies of natural anticoagulants (protein C, protein S and antithrombin III) and antiphospholipid syndrome (APS) in patients with early ST-segment elevation MI (STEMI). We recruited 255 consecutive patients who had survived a STEMI ≤ 35 years of age (224 men). The control group consisted of 400 healthy individuals matched with cases for age and sex. G20210A polymorphism of FII gene was more frequent in young patients than in controls (7.4 vs. 3.5%, p = 0.023). The odds ratio (OR) for STEMI for carriers versus non-carriers was 2.239 (95% CI 1.102-4.250). The adjusted OR for major cardiovascular risk factors was 2.569 (95% CI 1.086-6.074). The risk was increased by 22-fold (95% CI 9.192-66.517) when G20210A polymorphism was present in combination with smoking. There was no difference in the prevalence of FV Leiden between patients and controls (7.8 vs. 6.5%, p = 0.512). There was only one patient (0.4%) with protein C deficiency and one with APS (0.4%). G20210A polymorphism of FII gene may be associated with increased risk of premature STEMI and the risk increases substantially when smoking is present. The contribution of other prothrombotic disorders such as deficiencies of protein C, protein S and antithrombin III and APS was minimal in this cohort.

Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455G/A, FV HR2 + b-fibrinogen -455G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL.

Are inherited prothrombotic gene polymorphisms associated with lesion location in pediatric arterial ischemic stroke?

Objective: Pediatric arterial ischemic stroke (AIS) is a relatively rare disorder with multifactorial etiology. A variety of incompletely investigated genetic polymorphisms may cause hypercoagulability and lead to ischemic lesion formation in different parts of brain. As correlation between neuroimaging finding and genetic risk factors might be helpful for further therapeutic decisions, we investigated the significance of inherited prothrombotic gene polymorphisms in different pediatric AIS subtypes according to time of onset and lesion location. Methods: Eleven polymorphisms (FV Leiden, FV HR2, FII G20210A, β-fibrinogen −455G>A, FXIII-A Val34Leu, PAI-1 4G/5G, HPA-1, MTHFR C677T, MTHFR A1298C, ACE I/D, apoE ε2-4) were genotyped using a multilocus CVD Strip assay (ViennaLab, Austria) in DNA extracted from blood samples of 112 children (46 girls, 66 boys) with perinatal (N = 51) and childhood AIS (N = 61), and 110 sex- and age-matched controls. Results: FV Leiden (OR: 4.24; 95% CI: 1.16–15.46, p = 0.015) and ACE I/D (OR: 1.90; 95% CI: 1.01–3.55, p = 0.044) were found to be associated with AIS. Stroke localization data collected from patient medical records and magnetic resonance imaging results indicated cortical stroke in 69 children (39 with perinatal; 30 with childhood AIS) and subcortical stroke in 43 children, being more frequent in childhood (N = 31), compared to perinatal AIS (N = 12). Cortical and subcortical strokes differed in β-fibrinogen −455G>A genotype distributions (p = 0.026), −455AA genotype was identified in cortical stroke only. Difference in PAI-1 4G/5G genotype distributions was found between childhood and perinatal subcortical stroke (p = 0.028), yielding to a 4.80-fold increased risk for childhood subcortical stroke (95% CI: 1.16–19.92). Conclusion: Obtained results corroborate previously reported FV Leiden association with AIS (Coen Herak et al. Clin Appl Thromb/Hemost, in press) with additional ACE I/D association. Exclusive associations of β-fibrinogen −455AA genotype with cortical stroke and PAI-1 4G/5G with childhood subcortical stroke support the assumption that specific polymorphisms may contribute to location dependant lesion formation.

Thrombophilia risk is not increased in children after perinatal stroke

AbstractPerinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging–classified neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or fetal periventricular venous infarction (PVI) were recruited. Standardized thrombophilia evaluations were performed after 12 months of age on stroke cases and controls, including quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocysteine, lupus anticoagulant, anticardiolipin antibodies and genotyping of factor V Leiden (FVL), factor II G20210A (FII), and methylenetetrahydrofolate reductase C677T. A total of 212 children were studied: 46 with NAIS, 34 with APPIS, 55 with PVI, and 77 controls (male, 53%; median age, 4.8 years). Of 14 parameters, no differences were observed in 12, including all common thrombophilias. Mean prothrombin time was shorter in arterial strokes (P < .001). Rates of antiphospholipid antibodies were low, comparable to those in controls, and resolved on repeat testing. FVL and FII rates were comparable to population norms. Total number of possible abnormalities did not differ between cases and controls. Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated.

Diagnostic Testing Approaches for Activated Protein C Resistance and Factor V Leiden: A Comparison of Institutional and National Provider Practices.

To analyze the economic impact of testing for activated protein C resistance (APC-R) due to factor V Leiden (FVL) mutation with APC-R with reflexive FVL genotyping (algorithmic approach) or genotyping alone. OptumLabs Data Warehouse (OLDW) data were used to assess testing approaches. Insurance claims for APC-R and FVL in 2013 were compared with the Mayo Clinic database. Centers for Medicare & Medicaid Services diagnostic fee schedules were used to assign costs. Of 19.3 million OLDW-covered individuals, 74,242 (0.385%) received 75,608 tests: APC-R, 2,265 (2.9%); FVL genotyping, 70,619 (90.1%); and both APC-R and FVL, 2,724 (7.0%). In total, 1,317 tests were performed at Mayo Clinic: APC-R with reflex FVL (1,256; 95.4%) and FVL alone (61; 4.6%). Costs per evaluated individual and per total population (person/year) in OLDW and algorithmic approach were $83.77 vs $36.38 and $0.32 vs $0.14, respectively. The cost-optimized algorithmic approach reduces health care costs.

New functional assays to selectively quantify the activated protein C‐ and tissue factor pathway inhibitor‐cofactor activities of protein S in plasma

Background Protein S plays an important role in the down-regulation of coagulation as cofactor for activated protein C (APC) and tissue factor pathway inhibitor (TFPI). Aim To develop functional assays to quantify the APC- and TFPI-cofactor activities of protein S in plasma. Methods APC- and TFPI-cofactor activities of protein S in plasma were measured using calibrated automated thrombography in protein S-depleted plasma supplemented with a small amount of sample plasma either in the presence of anti-TFPI antibodies and APC (APC-cofactor activity) or at excess full-length TFPI without APC (TFPI-cofactor activity). Total and free protein S levels in plasma were measured by ELISAs. Results Average APC-cofactor activities of protein S were 113%, 108% and 89% in plasma from normal individuals (n = 15), FV Leiden heterozygotes (n = 14) and FV Leiden homozygotes (n = 7), respectively, whereas the average APC-cofactor activity of protein S in plasma from heterozygous protein S-deficient individuals (n = 21) was significantly lower (55%). Similar trends were observed for the TFPI-cofactor activity of protein S, with averages of 109%, 115% and 124% in plasma from individuals with normal protein S levels and different FV Leiden genotypes, and 64% in plasma from protein S-deficient patients. APC-cofactor activities of protein S correlated significantly with free and total protein S antigen levels, whereas TFPI-cofactor activities correlated less with protein S antigen levels. Conclusion We have developed functional protein S assays that measure both the APC- and TFPI-cofactor activities of protein S in plasma, which are hardly if at all affected by the FV Leiden mutation.

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

BackgroundFamilial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentationCase 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months.ConclusionsIdiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

Incidence of the genetic mutations in patients with coronary artery disease

Objectives . Coronary artery disease (CAD) is the leading cause of mortality in the world. It is a complex disorder resulting from the interaction between environmental risk factors and hereditary predisposition. The role of the factor V Leiden (FVL), protrombin gene (PT G20210A) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in the development of CAD is controversial. In this study, we investigated the incidence of these polymorphisms in order to delineate their roles in the development of CAD in a tertiary University hospital. Methods. This study included 58 consecutive CAD patients. Diabetic and hypertensive patients were excluded. FVL, PT G20210A, and MTHFR (C677T, A1298C) mutations were investigated in all patients. Polymerase chain reaction and the amplification refractory mutation system were used to identify these polymorphisms. Results. Thirty-six men and 22 women were enrolled with an age ranging between 41 to 85 (mean age: 62.75±9.18 years). The heterozygous PT G20210A genotype was identified in 5 (8.6%) patients (2 males, 3 females). The heterozygous FVL genotype was found in 8 (13.8%) patients (6 males and 2 females). The incidence of homozygous MTHFR C677T and homozygous MTHFR A1298 carriers was found to be 17.2% and 8.6%, respectively. There were no significant differences in the distribution of polymorphisms according to gender ( p >0.05). Conclusions. The FVL and PT G20210A polymorphisms most likely play a contributory role in the development of CAD. In contrast, the MTHFR C677T and MTHFR A1298C genotypes were not associated with a predisposition to the development of CAD. However, in compound MTHFR C677T/A1298C carriers, the presence of FVL or PT G20210 polymorphism may contribute the development of CAD. Further studies are needed to support these findings.

Lack of rivaroxaban influence on a prothrombinase-based assay for the detection of activated C protein resistance: an Italian ex vivo and in vitro study in normal subjects and factor V Leiden carriers.

Activated protein C resistance (APCr) leads to hypercoagulability and is due, often but not exclusively, to Factor V Leiden (FVL). The aim of this study was to assess the ex vivo and in vitro interference of the direct factor Xa inhibitor rivaroxaban (RIV) on a prothrombinase-based assay for APCr detection. An ex vivo study was performed on fresh plasma samples obtained from 44 subjects with FV wild-type and seven with FVL heterozygous, all treated with RIV. An in vitro study was performed on 15 plasma samples (six from normal subjects, six from heterozygous, and three from homozygous FVL carriers, all frozen specimens) spiked with RIV. RIV concentration was evaluated using a chromogenic assay, and APCr was evaluated by a prothrombinase-based assay. No significant interference of RIV on APCr results obtained by a prothrombinase-based assay was observed for drug concentrations up to 400 ng/mL in FV wild-type and FVL carriers (homozygous and heterozygous). These results were confirmed both ex vivo and in vitro. RIV did not significantly interfere with the prothrombinase-based assay used for the assessment of APCr, and this was observed to occur independently of FV status. However, only concentrations up to 400 ng/mL were tested and, therefore, what occurs in the presence of higher doses remains to be investigated.

Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients.

We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) and a genetic predisposition for ischemic stroke. Twenty-eight stroke and/or TIA subjects (33-63years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVA and QPFO at rest and during supine exercise with and without breathing 100% O2 . We also examined genetic polymorphisms in FV Leiden (G1691A; rs6025), factor II (FII) prothrombin (G20210A; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen-activator inhibitor-1 (PAI-1) (4G/5G; rs1799889) and angiotensin-converting enzyme (ACE; I/D, rs4646994) in 24/28 subjects. No subject without PFO had QIPAVA at rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFO at rest (n=11) and 7/11 had either QIPAVA or QPFO with exercise. Breathing 100% O2 during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence. Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.

A case of pulmonary thromboembolism due to coagulation factor V Leiden in Japan\u2009~\u2009usefulness of next generation sequencing~

BackgroundBecause the venous thromboembolisms (VTEs) due to the coagulation factor V R506Q (FV Leiden) mutation is often seen in Caucasians, the VTE onset in Japan has not been reported.Case presentationA 34-year-old man from north Africa experiencing sudden dyspnea went to a hospital for advice.The patient had pain in his right leg and a high plasma D-dimer level. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the right lower extremity. The patient was diagnosed with VTE, and anticoagulation therapy was initiated. Our targeted gene panel sequencing revealed that the occurrence of VTE was attributed to a presence of the FV Leiden mutation.ConclusionsThis is the first report demonstrating VTE caused by the FV Leiden mutation in Japan.

Gender-related differences in the outcome of patients with venous thromboembolism and thrombophilia

In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.

P-043: Genes polymorphism FV Leiden G1691A, FII G20210A, MTHFR C677T and PAI-1 5G/4G in patients with miscarriages and inherited thrombophilia – experience from our clinic

P-043: Genes polymorphism FV Leiden G1691A, FII G20210A, MTHFR C677T and PAI-1 5G/4G in patients with miscarriages and inherited thrombophilia – experience from our clinic

Reduced prothrombinase inhibition by tissue factor pathway inhibitor contributes to the factor V Leiden hypercoagulable state

AbstractActivated factor V (FVa) and factor X (FXa) form prothrombinase, which converts prothrombin to thrombin. The α isoform of tissue factor pathway inhibitor (TFPI) dampens early procoagulant events, partly by interacting with FV. FV Leiden (FVL) is the most common genetic thrombophilia in whites. Thrombosis risk is particularly elevated in women with FVL taking oral contraceptives, which produce acquired TFPIα deficiency. In mice, FVL combined with a 50% reduction in TFPI causes severe thrombosis and perinatal lethality. However, a possible interaction between FVL and TFPIα has not been defined in humans. Here, we examined this interaction using samples from patients with FVL in thrombin generation and fibrin formation assays. In dilute TF- or FXa-initiated reactions, these studies exposed a TFPI-dependent activation threshold for coagulation initiation that was greatly reduced by FVL. The reduced threshold was progressively overcome with higher concentrations of TF or FXa. Plasma assays using anti-TFPI antibodies or a TFPI peptide that binds and inhibits FVa, demonstrated that the decreased activation threshold resulted from reduced TFPIα inhibition of prothrombinase. In assays using purified proteins, TFPIα was a 1.7-fold weaker inhibitor of prothrombinase assembled with FVL than with FV. Thus, FVL reduces the threshold for initiating coagulation, and this threshold is further reduced in situations of low TFPIα concentration. Individuals with FVL are likely prone to thrombosis in response to weak procoagulant stimuli that would not initiate blood clot formation in individuals with FV.

Atherosclerotic and thrombotic genetic and environmental determinants in Egyptian coronary artery disease patients: a pilot study

BackgroundCoronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Multiple genetic variants in combination with various environmental risk factors have been implicated. This study aimed to investigate the association of twelve thrombotic and atherosclerotic gene variants in combination with other environmental risk factors with CAD risk in a preliminary sample of Egyptian CAD patients.MethodsTwenty three consecutive CAD patients undergoing diagnostic coronary angiography and 34 unrelated controls, have been enrolled in the study. Genotyping was based on polymerase chain reaction and reverse multiplex hybridization. Five genetic association models were tested. Data distribution and variance homogeneity have been checked by Shapiro-Wilk test and Levene test, respectively; then the appropriate comparison test was applied. Spearman’s rank correlation coefficient was used for correlation analysis and logistic regression has been performed to adjust for significant risk factors. Clustering the study participants according to gene-gene and gene-environment interaction has been done by Detrended Correspondence Analysis (DCA).ResultsThe univariate analysis indicated that the five variants; rs1800595 (FVR2; factor 5), rs1801133 (MTHFR; 5,10-methylenetetrahydrofolate reductase), rs5918 (HPA-1; human platelet antigen 1), rs1799752 (ACE; angiotensin-converting enzyme), and rs7412 and rs429358 (ApoE; apolipoprotein E) were significantly associated with CAD susceptibility under different genetic models. Multivariate analysis revealed clustering of the study population into three patient groups (P) and one control group. FVR2 was the most variant associated with CAD patients, combined with the factor V Leiden (FVL) variant in P1 cluster and with both ACE and MTHFR 667C > T in P2. Whereas, P3 was mostly affected by both MTHFR 667C > T and FXIII (factor 13) V89L mutations. When combined with traditional risk factors, P1 was mostly affected by dyslipidemia, smoking and hypertension, while P2 was mostly affected by their fasting blood sugar levels and ApoE variant.ConclusionsTaken together, these preliminary results could have predictive value to be applied in refining a risk profile for our CAD patients, in order to implement early preventive interventions including specific antithrombotic therapy. Further large scale and follow-up studies are highly recommended to confirm the study findings.

Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India

Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7IU/ml, controls: 117.5 ± 17.7IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1IU/ml] and controls [102 ± 11.9IU/ml] were not statistically significant (p = 0.119). Anti β2 glycoprotein I (Anti-β2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-β2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.

The Role of Factor V Leiden 1691G&gt;A and Prothrombin Gene 20210G&gt;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.

Thrombophilic Mutations Among Patients with Sickle Cell Disease.

Factor V-Leiden (FVL), Prothrombin (PRT) G20210A, and Methylene Tetrahydro Folate Reductase (MTHFR) C677T and A1298C mutations are major inherited risk factors of thrombotic complications. Our aim in this study was to investigate the prevalence of these mutations among Tunisian sickle cell patients. Study subjects comprised 64 patients and 100 healthy controls. FVL, PRT G20210A, and MTHFR genotypes were determined using a reverse dot blot based method. In the patient population studied, the prevalence of FV Leiden was not statistically different from controls while a significant prevalence of heterozygous PRT G20210A mutation among patients (10.93%) was found. An increased frequency of the MTHFR 677 C>T genotype was seen among patients as well as controls. The results showed no significant association between the MTHFR A1298C mutation and sickle cell disease (SCD). However, the prevalence of carrier among studied patients was 15.62% compared to 7% among healthy subjects. In conclusion, our data suggest a significant association between PRT G20210A and MTHFR C677T and sickle cell disease among Tunisian patients.

Thrombophilic Status of Extracted Fetal Tissues of Spontaneously Aborted Embroys

Objective : The reports about Factor V (FV) Leiden, Factor II (FII) G20210A and Methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations of parents and fetal viability are frequently encountered in the literature, despite the fetal side of thrombophilia is scant. To clarify the three common thrombophilic gene mutations of the spontaneously aborted embryos, an accurate algorithm was followed to extract the fetal tissues and then the mutations were searched. Material and Methods : 70 spontaneous abortion materials were included to the study and all were karyotyped. Cytogenetically abnormals were excluded from the study. To extract the fetal tissues, amplifications of sex determination region of chromosome-Y (SRY) gene and genotypings were performed, respectively. Extracted fetal tissues of spontaneous aborted embroys and parents were screened for the thrombophilic gene mutations via electronic microarray. Results: After excluding chromosomally abnormal and maternally contaminated ones totally ten fetal tissues were screened for the FII G20210A, FV Leiden and MTHFR C677T gene mutations, and two carry F II G20210A and F Leiden heterozygote mutations, and six carry heterozygote forms of MTHFR C677T. Conclusion : The present study performed on the limited number of abortion materials, has a value for distinguishing the fetal tissues before analyzing the three common mutation of thrombophilic genes which make the results are very substantial.

Genetic Markers of Hereditary Thrombophilia and Risk of Thrombotic Complications in Patients with Polycythemia Vera

Background. Thrombotic complications are one of the main problems of polycythemia vera (PV) treatment. They significantly impair the quality of life of these patients and may lead to the lethal outcome. A thrombotic event often precedes the diagnosis of this hematological disease. The pathogenesis of thrombosis in myeloproliferative neoplasms, PV, in particular, is a complex one. Prescription of antiaggregants in the absence of thrombosis and anticoagulants after a thrombotic event requires special attention and development of corresponding recommendations. The prescription of anticoagulants is impossible without taking into account the risks of hemorrhagic complications, which are also typical for myeloproliferative neoplasms. Aim. Assessment of the impact of hereditary thrombophilia genetic markers on the risk of thrombotic complications in patients with PV. Methods. The study examined 116 patients with PV, who were screened for markers of hereditary thrombophilia: factor V (G1691A, FV Leiden), prothrombin, methylene-tetrahydrofolate reductase (MTHFR), fibrinogen (F/), plasminogen activator inhibitor (PA/-1), and platelet fibrinogen receptor type ///A (GP///A). The incidence of these markers and their role in thrombosis in such patients was investigated. Results. The study provided data on the incidence of hereditary thrombophilia markers in patients with PV. Statistically significant differences in the incidence of these markers and homocysteine level were found between patients with thrombosis and without them. Conclusion. The information about the hereditary thrombophilia markers presence may be useful for the prescription of adequate antiaggregant and anticoagulant therapy for PV patients. Further research in this field is justified and it will probably demonstrate the relevance of hereditary thrombophilia markers as prognostic factors for thrombotic complications risk assessment.