Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke

The association between factor V Leiden (FVL) and prothrombin G20210A (PT 20210) mutations and ischemic stroke remains controversial, particularly in young adults with cryptogenic stroke. Prevalence of FVL (4.1%) and PT 20210 (8.2%) mutations was assessed in 49 patients under 50 years with cryptogenic stroke and compared with controls. Odd ratio (OR) for cryptogenic stroke was 2.62 (95% CI, 0.49-13.95) for FVL and 3.75 (95% CI, 1.05-13.34) for PT 20210 and 3.28 (95% CI, 1,17-9.20) for some recognized genetic thrombophilic defect. Moreover, the OR for cryptogenic stroke in young women using oral contraceptives (OC) was 3.59 (95% CI, 1.28-10.5).When some genetic thrombophilic defect was associated with OC, the OR was much higher (OR: 14.27; 95% CI, 0.66-309.99). Our results suggest that in the Mediterranean populations the PT 20210 mutation, but not FV Leiden, is a risk factor for cryptogenic stroke in young adults. OC use is also a significant risk factor for cryptogenic stroke, which is increased in women with some genetic thrombotic risk factor.     

Prothrombin 20210A and oral contraceptive use as risk factors for cerebral venous thrombosis

BACKGROUND: This study investigates the association between cerebral vein thrombosis (CVT) and the mutations FV 1691A (factor V Leiden), PT 20210A and MTHFR 677TT and acquired factors including oral contraceptive (OC) use. METHODS: 26 patients (21 females) and 217 healthy controls (134 females) were studied. Multiple regression analysis was performed. RESULTS: The frequency of the three mutations in cases and controls were: PT 20210A, 23 versus 1%, odds ratio (OR) 21.40 (95% CI 4.29-118.75), p < 0.001; FV 1691A, 8 versus 1%, OR 5.94 (95% CI 0.66-46.9); MTHFR 677TT, 4 versus 7%, OR 0.54 (95% CI 0.03-4.08). OC use was more frequent in female patients over 14 years old than in controls (84 vs. 40%, OR 8.15, 95% CI 2.09-37.13, p < 0.001). The model that best explained the thrombotic risk included PT 20210A and OC use. CONCLUSIONS: PT 20210A and OC use are the main thrombophilic risk factors predisposing to CVT and should be routinely investigated in patients with this disease.     

Factor V Leiden and prothrombin gene G20210A mutation in children with venous thromboembolism

To determine whether factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) are risk factors for venous thromboembolism (VTE) in Argentinean children. One hundred and thirty consecutive children with VTE were prospectively assisted at a single centre. Blood samples were available from 110 of them for detailed haematological analysis. The prevalence of both mutations was compared with a control group. The odds ratio for VTE was significantly increased in patients with FVL (OR 3.64; 95% CI: 1.14-11.6, p < 0.029) whereas odds ratio for VTE was not significantly increased in patients with PT20210A (OR 1.06; 95% CI: 0.24-4.73, p = 0.938). Combined disorders were found in 5 of the 10 children with the aforementioned mutations. In 21 children (19%) without these mutations other inherited and acquired disorders were detected. Our data show that FVL is a risk factor for VTE whereas PT20210A does not seem to be a risk factor in our paediatric population.     

Thrombophilic polymorphisms – factor V Leiden G1691A,prothrombin G20210A and MTHFR C677T – in Tunisian patients with cerebral venous thrombosis

Cerebral venous thrombosis (CVT) has been associated with thrombophilic defects. We performed a study to evaluate the role of three single nucleotide polymorphisms (SNP), factor V Leiden G1691A (FVL), prothrombin gene mutation G20210A (FII-G20210A) and methylenotetrahydrofolate reductase variant C677T (MTHFR-C677T), as risk factors for CVT in Tunisian patients. A single center case-control study (26 patients with CVT and 197 controls) was performed. Genomic DNA was tested for the three SNP. The principle finding was the association between FVL and CVT (p < 0.001, Odds ratio = 6.1, 95% confidence interval = 2.3–16.5). However, neither the FII-G20210 (p = 0.536) nor the homozygous MTHFR-C677T genotype (p = 0.325) variant contributed to the risk of CVT in these Tunisian patients.     

Prothrombin G20210A mutation,but not factor V Leiden,is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia

BACKGROUND: Paradoxical embolism via persistent foramen ovale (PFO) is suspected to be a frequent cause of stroke in younger patients. We investigated whether the prevalence of the risk factors for venous thrombosis factor V Leiden (FVL) and prothrombin G20210A mutation (PT G20210A) is increased in this group of patients. METHODS: We examined FVL and PT G20210A mutation in 220 patients (group 1) with cerebral ischemia associated with a PFO and without other etiology, in 196 patients with cerebral ischemia of an etiology other than PFO (group 2), and in 362 healthy subjects (group 3) from the same region in Germany. RESULTS: Heterozygosity for the PT G20210A mutation was more common in group 1 (5.0%) than in group 3 (1.4%; sex- and age-adjusted odds ratio 3.66; 95% CI 1.25-10.75; p = 0.01). By contrast, the mutation was not more common in group 2 (2.6%; odds ratio 1.50; 95% CI 0.42-5.41; p = 0.5). Prevalences of FVL were not different between groups. CONCLUSIONS: We identified PT G20210A but not FVL - the strongest genetic risk factor for deep venous thrombosis - to be significantly associated with stroke attributed to PFO. These findings rise doubts about the concept of paradoxical brain embolism as the dominating mechanism in stroke associated with PFO.     

An unfavorable combination of Factor V Leiden with age, weight, and blood group causes high risk of pregnancy-associated venous thrombosis: a population-based nested case-control study

INTRODUCTION: Hereditary and acquired risk factors increase the risk for thrombosis among pregnant women. Few risk estimates are, however, well established. The aim of the present study was to assess risk for pregnancy-associated venous thrombosis of factor V Leiden (FVL), FII G20210A, FV A4070G, MTHFR C677T, TFPI C536T, PROC T38853G, FXIII V34L, blood group, age, and body mass index (BMI), and their interactions and public health impact. MATERIALS AND METHODS: Study design is a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Thirty four cases with objectively diagnosed venous thrombosis and 641 controls were studied. RESULTS: FVL (OR 11.6, 95% CI 3.6-33.6), age >35 vs. <25 (OR 6.3, 95% CI 1.7-23.1), and BMI >30 vs. <25 (OR 5.6, 95% CI 2.3-13.9) were associated with thrombosis. Overall absolute risk of a FVL carrier was 1 in 314. FVL interacted with age, BMI, and blood group. Population attributable risk proportion was 19% for FVL, 23% for age >35, 33% for BMI >25, and 35% for non-O blood group. Unexpectedly, the prevalence of FVL increased with age in controls. CONCLUSIONS: FVL appeared as a strong risk factor for pregnancy-associated venous thrombosis. Especially in elderly overweight mothers, FVL may cause a substantial thrombosis risk. Further studies are needed to confirm the increased prevalence of FVL in elderly mothers with normal pregnancies.     

Genetic variation in thrombin-activatable fibrinolysis inhibitor (TAFI) is associated with the risk of splanchnic vein thrombosis

Splanchnic vein thrombosis (SVT) has been associated with a hypercoagulable state. Thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to a hypercoagulable state, and therefore we were interested in the role of TAFI in SVT. Since the disease is frequently associated with liver insufficiency, which affects plasma levels of TAFI, we studied the role of variation in the TAFI gene in SVT. In a multicenter case-control study on 118 patients with SVT (39 Budd-Chiari syndrome and 85 portal vein thrombosis) and 118 population-based controls, the relationship of SVT with single nucleotide polymorphisms (SNPs) and haplotypes in the TAFI gene (-438G/A, Ala147Thr, Thr325Ile and 1583A/T) was determined. The risk for SVT was decreased (OR 0.2, 95% CI 0.1-0.7) in 147Thr/Thr homozygotes and slightly, but not significantly, increased in carriers of the 325Ile allele (OR 1.6, 95%CI 0.9-2.7). Haplotype analysis confirmed that the Ala147Thr SNP has the strongest association with risk of SVT. In conclusion, genetic variation in the TAFI gene is associated with risk of SVT, suggesting a role for TAFI in the pathogenetic mechanism of SVT.     

Elevated prothrombin is a risk factor for cerebral arterial ischemia in young adults

The prevalence of elevated prothrombin (PT) in the absence of the G20210A mutation has not been studied in patients with cerebral ischemia. We carried out a case-control study of PT G20210A and PT activity in 49 adult patients aged 45 years or less, with TIA or ischemic stroke without cardiac embolism or large vessel disease, and 87 controls from a group of blood donors. Five patients were heterozygous for PT 20210A (OR=2.3, 95% CI: 0.6–8.0). Even after exclusion of individuals with the PT gene variant, the PT activity was significantly higher in patients than in controls (1.11 vs. 0.97, P=0.0003). The relative risk of cerebral ischemia in patients within the fourth quartile of PT activity (1.10 U/ml or higher), was 3.2 fold (95% CI: 1.03–9.96), than in patients whose level of PT activity was in the second or third quartile. We conclude that, although PT 20210A may be a weak risk factor for TIA and ischemic stroke in young patients, increased PT activity, which is more frequent than the mutation, appears to be more strongly related to cerebral ischemia.     

Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes

The prevalence of the A20210 allele of the prothrombin (PT) gene and the T677 allele of the methylene tetrahydrofolate reductase (MTHFR) gene was determined in 205 patients with venous thromboembolism (VTE) and in 398 healthy subjects of similar age and sex distribution. We also determined the frequency of these two candidate risk alleles in subjects carrying the factor V (FV) Q506 allele, to identify a possible interaction. Forty patients (19.5%) and 14 control subjects (3.5%) were heterozygous for the FV R506Q mutation. Twenty-one patients (10.2%) and 11 controls (2.8%) were heterozygous for the PT A20210 allele (odds ratio (OR) 4.02, 95% confidence interval (CI): 1.90-8.50, p <0.001). This confirmed that the PT A20210 allele was a risk factor for VTE in our population. Among the FV Q506 allele carriers, 9 patients (22.5%) and no control also had the PT gene G20210A mutation. The absence of the combined abnormality in the control group made it impossible to calculate the relevant ORs but the lower bound of the 95% CI was 3.94, suggesting that individuals bearing the two mutations have a higher risk than those with a single mutation. Twenty-six patients (12.7%) and 49 controls (12.3%) were homozygous for the MTHFR T677 allele (OR 1.04, 95% CI: 0.62-1.72, not significant). Four patients and 1 control were also heterozygous for the FV R506Q mutation (OR 9.33, 95% CI: 1.03-84.23). However, the ORs for carriers of the FV R506Q mutation were not significantly influenced by MTHFR gene C677T homozygosity.     

Hyperhomocysteinemia and other newly recognized inherited coagulation disorders (factor V Leiden and prothrombin gene mutation) in patients with idiopathic cerebral vein thrombosis

BACKGROUND: Idiopathic cerebral vein thrombosis (iCVT) represents approximately 30% of the cases of cerebral vein thrombosis (CVT). New, inherited - factor V Leiden (FVL) and prothrombin gene mutation (PTHRA20210) - and inherited/acquired - hyperhomocysteinemia (HHcy) - prothrombotic conditions have been detected recently. METHODS: We assessed fasting plasma homocysteine (Hcy) levels and main Hcy determinants, FVL and PTHRA(20210) in 30 patients with documented iCVT and 40 age- and sex-matched healthy subjects. RESULTS: A strong and significant association of PTHRA(20210) [30% (9/30) vs. 2.5% (1/40) iCVT vs. controls, respectively, p = 0.001; OR = 16.174, p = 0.002] and HHcy [13/30 (43.3%) vs. 4/40 (10%) iCVT vs. controls, respectively; p = 0.002, OR = 6.88, p = 0.002] with iCVT was found. CONCLUSIONS: PTHRA(20210) and HHcy should be considered when screening for thrombophilia and should be assessed in patients with a family or personal history of CVT.     

Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children

BACKGROUND AND PURPOSE: The association between ischemic childhood stroke and thrombophilia has been debated. We studied the prevalence of thrombophilia risk factors in 65 unrelated children with ischemic stroke compared with 145 control subjects. METHODS: Patients and control subjects were tested for antithrombin protein C and protein S deficiencies, the presence of antiphospholipid antibodies (APLA), factor V Leiden (FVL), G20210A polymorphism of factor II gene (FII G20210A), and C677T polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR). RESULTS: Of 65 children, 7 had a stroke in the neonatal/perinatal period and therefore were analyzed separately. Thirty-one of the remaining 58 patients with pediatric stroke (53.4%) were found to have at least 1 thrombophilia marker compared with only 25.5% of control subjects. None of the patients or control subjects had protein S or antithrombin III deficiency. The prevalence of protein C deficiency was higher among pediatric stroke patients than among control subjects, but the difference was not statistically significant (OR=7, 95% CI 0.75 to 65.1). Heterozygous FII G20210A and homozygous MTHFR 677T were not associated with an increased risk for stroke (OR=1.29, 95% CI 0.2 to 8.2; and OR=1.06, 95% CI 0.4 to 2.7, respectively). In contrast, the presence of APLA was associated with a >6-fold risk of stroke (OR=6. 08, 95% CI 1.5 to 24.3), and the heterozygosity for FVL increased the risk of stroke by almost 5-fold (OR=4.82, 95% CI 1.4 to 16.5). Five patients with pediatric stroke had a combination of > or =2 thrombophilia markers, whereas none of the control subjects had a combination of the markers. Most of the patients with neonatal/perinatal stroke were found to have at least 1 thrombophilia marker. CONCLUSIONS: These data suggest that the prevalence of thrombophilia markers is increased in children with stroke compared with control subjects and, specifically, that FVL and APLA contribute significantly to stroke occurrence.     

Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk

The role played by a hypercoagulable state, either inherited or acquired, in the pathogenesis of upper-extremity deep vein thrombosis (UEDVT) remains a question of debate. We performed a case-control study including 79 patients with a first objectively confirmed episode of UEDVT, 31 secondary and 48 primary, and 165 healthy controls. Nine patients (11.4%) with UEDVT were carriers of the prothrombin G20210A mutation vs. six (3.7%) in controls; P = 0.025, OR: 3.39 (95% CI 1.16 to 9.88). No statistical difference was observed between cases and controls for the factor V Leiden mutation, AT, protein C or protein S deficiency and anticardiolipin antibodies (ACAs).Thirteen (35.1%) UEDVT patients were oral contraceptive (OC) users vs. 12 (16%) controls; P = 0.020, OR: 2.89 (95% CI 1.16-7.21). When secondary UEDVT patients were compared with controls, no differences were observed in any of the risk factors analysed. On the other hand, when primary UEDVT was considered, six (12.5%) patients were carriers of the prothrombin G20210A mutation vs. six (3.7%) controls; P = 0.031, OR: 3.76 (95% CI 1.15-12.26). Regarding ACAs, a borderline statistical significance was observed when primary UEDVT was compared with controls, P = 0.048; OR: 4.88 (95% CI 1.05-22.61). In primary UEDVT, 52% of the fertile women were OC users vs. 16% of controls; P = 0.001, OR: 5.78 (95% CI 2.13-15.67). When the interaction of both factors, i.e. prothrombin G20210A mutation and OC intake, were considered, the risk increased markedly, indicating a synergistic effect as observed with other thrombotic locations. In patients with primary UEDVT screening for antithrombin, protein C and protein S deficiency and APC resistance would not be justified, although it might be reasonable to determine the carrier status of the prothrombin G20210A mutation only in OC users.     

Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels

High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5-1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9-2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.     

Haplotypes of TAFI gene and the risk of cerebral venous thrombosis - a case-control study

Introduction

Cerebral venous thrombosis (CVT) is an uncommon disease with some differences compared to other-site thrombosis, including a higher frequency in young people, female sex and oral contraceptive users. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a regulator of fibrinolysis, whose levels are genetically controlled and its increase is associated to thrombosis. Our objective was to investigate in a case-control study the association between CVT and TAFI single nucleotide polymorphisms (SNPs) and its haplotypes in comparison to other-site venous thrombosis and controls.

Materials and Methods

Seventy two patients with CVT were compared to 143 individuals with no history of thromboembolic events (control group) and to 128 patients with deep vein thrombosis in the limbs and/or pulmonary embolism (venous thromboembolism-VTE group). SNPs were genotyped by restriction fragment length polymorphism or allele-specific PCR for F2 20210G > A, F5 1691G > A, TAFI (-1053C > T, -438G > A, 505G > A, 1040C > T and + 1542C > G).

Results

The GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs was associated with an increased risk of CVT compared to controls [odds ratio (OR) 2.67, 95% confidence interval (CI): 1.13 - 6.34) and VTE group (OR 2.51, 95%CI: 1.07 - 8.06). The CVT risk became even more pronounced when evaluating unprovoked or hormone-related thrombosis cases: CVT compared to controls (OR 3.24, 95%CI: 1.19 - 8.82) and VTE group (OR 4.32, 95%CI: 1.27 - 14.63).

Conclusions

Our data indicate that the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs increased the risk of CVT in comparison to controls and VTE cases. Further studies are required to confirm our findings.     

Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults

Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95?% CI 0.78–1.38) or in the dominant model (OR 1.24; 95?% CI 0.72–2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.     

Major and potential prothrombotic genotypes in a cohort of patients with venous thromboembolism.

Factor V Leiden (FVL) and the prothrombin 20210A (PT-20210A) variant are well-known risk factors for venous thromboembolism (VT). The thermolabile variant (TT) of the methylenetetrahydrofolate reductase (MTHFR) gene, and homozygosity for the 4G allele of the promoter region of the plasminogen activator inhibitor-1 (PAI-1) are potential genetic polymorphisms that have not been consistently associated with increased risk of VT. A case-control study was performed on 192 consecutive unrelated patients referred for evaluation of thrombophilia because of VT and 200 healthy controls. FVL was found in 10.4% of patients compared to 3.0% of controls, while 6.3% of patients were carriers of the PT-20210A allele compared to 2.0% of controls. The adjusted odds ratios (OR) were 5.92 and 4.03 for FVL (P=.001) and the PT-20210A (P=.033), respectively. The prevalence of homozygotes for MTHFR (TT) and PAI-1 (4G/4G) among patients and controls were 13.7% versus 13.0% and 21.6% versus 23.5%, respectively (P=ns). A total of 121 patients underwent a complete screening for FVL, the PT-20210A, protein C (PC), protein S (PS), antithrombin III (ATIII), levels of factor VIII, and antiphospholipid antibodies (aPL). In 59 patients (48.8%) at least one defect was found, being a single defect in 55 and combined defects in 4 patients. Plasma levels of homocysteine (Hcy) were measured in 138 patients and 144 controls. Subjects from both groups carrying the MTHFR-TT variant had higher Hcy levels than those with the normal genotype. Hyperhomocysteinemia (HHcy) by itself is a risk factor for VT (OR 4.92, P<.0001). We conclude that FVL and the PT-20210A are risk factors for VT as well as Hcy levels, but the MTHFR and PAI-1 polymorphisms do not appear to be associated with VT in our country.     

Low protein Z levels but not the protein Z gene G79A polymorphism are a risk factor for ischemic stroke

Background

Protein Z (PZ) is a vitamin K-dependent plasma protein that plays a role in both pro-and anticoagulant pathways, but its exact physiological function remains unclear. The aim of this study was to determine the association between the G79A PZ gene polymorphism in intron F, PZ levels and the occurrence of ischemic stroke.

Methods

We performed a case-control study in 118 Caucasian patients with first ever ischemic stroke or TIA confirmed by CT, and 113 age-and sex-matched population controls. Venous blood samples for PZ levels were collected 7 to 14 days and 3 months after stroke onset. Estimates of relative risk (odds ratios) were adjusted for vascular risk factors.

Results

The adjusted relative risk of ischemic stroke associated with PZ levels in the lowest quartile versus the highest quartile was 3.0 (95% CI: 1.1-8.7) at 7-14 days, and 5.1 (95% CI: 1.2-21.9) at 3 months after the stroke. PZ levels in the convalescent sample were significantly lower than in the acute sample. In the convalescent sample, odds ratios increased with lower quartiles of protein Z level (test for trend p = 0.02). Thirty-nine patients (33%) and 32 (28%) controls were heterozygous for the G79A PZ gene polymorphism and 4 (3%) patients and 4 (4%) controls had the AA-genotype. The PZ levels were significantly lower in subjects with the AA-genotype and intermediate in heterozygote subjects. The odds ratio of ischemic stroke associated with A-allele carriers versus GG-homozygotes was 1.2 (95% CI: 0.7-2.1).

Conclusion

No association between the G79A PZ gene polymorphism and the occurrence of stroke was observed. However, low PZ levels are independently associated with an increased risk of ischemic stroke.     

Inherited thrombophilic abnormalities and risk of portal vein thrombosis. a meta-analysis

Inherited thrombophilic abnormalities may have a role in the development of portal vein thrombosis (PVT). However, the prevalence of these factors in patients with PVT has been evaluated only in small studies with non-conclusive results. It was the purpose of this study to assess the risk of PVT associated with factor V Leiden (FVL) and G20210A prothrombin mutation (PTM). The MEDLINE, EMBASE, Cochrane Library databases, reference lists of retrieved articles and contact with content experts were used. Studies carried out in Western Europe comparing the prevalence of prothrombotic abnormalities in patients with PVT and in controls without a history of thromboembolic disease were included. Two reviewers independently selected studies and extracted study characteristics, quality and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a fixed and random-effects model. Statistical heterogeneity was evaluated using the I(2) statistic. Sensitivity analyses were performed examining separately studies according to the etiology of PVT and to control population. Twelve studies involving more than 3,000 patients were included. The pooled OR for PVT was 1.90 (95%CI: 1.25, 2.90) in patients with FVL and 4.48 (95%CI: 3.10, 6.48) in patients with PTM. In conclusion, PVT is associated with the presence of FVL and PTM in Western Europe.     

The role of inherited thrombophilia in patients with isolated pulmonary embolism: A systematic review and a meta-analysis of the literature

Introduction

Venous thromboembolism (VTE) is a common vascular disease that results in deep venous thrombosis (DVT) and pulmonary embolism (PE). Factor V Leiden mutation (FVL) and G20210A prothrombin mutation (PTM) are associated with an increased risk of VTE. Recent studies have reported a lower prevalence of FVL in patients with isolated PE than in patients with DVT with or without PE, suggesting the possibility that the prevalence of FVL in patients with isolated PE may be not significantly different from that of the general population. To address this issue, we performed a systematic review and a meta-analysis of published studies that assessed the prevalence of FVL and/or PTM in patients with isolated PE and in controls without VTE.

Methods

MEDLINE and EMBASE databases were searched up to October 2013. Pooled odds Ratios (OR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical heterogeneity was evaluated using the Cochran Q and I² statistics.

Results

Eighteen studies totalling more than 11,000 patients were included. FVL was found significantly more often in patients presenting isolated PE than in controls (OR 2.06; 95% CI 1.66, 2.56; p < 0.0001). The prevalence of PTM was also significantly different in patients presenting with isolated PE than in controls (OR 2.64, 95% CI 1.92, 3.63; p < 0.0001). Heterogeneity among studies was low.

Conclusion

FVL and PTM are both associated with isolated PE. However, the association magnitude between PE and FVL mutation appeared to be lower compared to that observed in the general population of VTE patients.