Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism

We determined the prevalence of factor V Leiden and of prothrombin G20210A mutations in a cohort of unselected outpatients (n = 748) referred for suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis of similar studies was also performed. Based on the clinical presentation, the prevalence of factor V Leiden was 15.7% in the 83 patients with DVT and 14.1% in the 99 patients with PE compared with 5.3% in patients without DVT and/or PE (control group). The prevalence of the prothrombin G20210A mutation did not differ among the three groups (3.9% for controls, 4. 8% for DVT and 3.9% for PE patients). We then divided the 99 patients with PE by separately analysing those with PE but without DVT (n = 57) and those with PE and DVT (n = 42). Compared with the control group, the prevalence of factor V Leiden was 10.5%, odds ratio (OR) 2.10 [95% confidence interval (95% CI) 0.68-5.45] in patients with primary PE and 19.1%, OR 4.20 (95% CI 1.54-10.30) in patients with DVT and PE. For the prothrombin G20210A mutation, no statistically significant differences were found between the control group and the three other groups. In conclusion, our data and the pooled analysis indicate that patients with primary PE are less often affected by the factor V Leiden mutation. No statistically significant differences were observed between patients and controls for the prothrombin G20210A mutation.     

A second mutation in the methylenetetrahydrofolate reductase gene and the risk of venous thrombotic disease

We assessed the effect of a recently described mutation in the MTHFR gene (1298 A --> C) on the risk of deep venous thrombosis (DVT) by determining its prevalence in 190 patients with verified DVT and in age-, race- and gender-matched controls. MTHFR 1298 A --> C was found in 42.1% of patients and in 41.1% of controls. The OR for venous thrombosis was 1.07 (95% CI 0.70-1.65) for heterozygotes and 0.83 (95% CI 0.33-2.08) for homozygotes. The OR for the factor V Leiden (FVL) mutation was 3.40 (95% CI 1.22-9.48), for FII 20210 G --> A was 5.22 (95% CI 1.12-24.2) and for MTHFR 677 C --> T, 1.24 (95% CI 0.82-1.87). No significant increased risk for venous thrombosis was found when MTHFR 1298 A --> C was coinherited with FVL (OR 2.85, 95% CI 0.88-9.23), FII 20210 G --> A (OR 7.19, 95% CI 0.87-59.4) or MTHFR 677 C --> T (OR 1.44, 95% CI 0.71-2.92). These data do not support a critical role of MTHFR 1298 A --> C in the predisposition to DVT.     

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives

BACKGROUND AND OBJECTIVES: The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances. DESIGN AND METHODS: A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. RESULTS: Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly. INTERPRETATION AND CONCLUSIONS: The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.     

Coexistence of factor V G1691A and factor II G20210A gene mutations in a thrombotic family is associated with recurrence and early onset of venous thrombosis.

Two G-to-A mutations at positions 1691 of the factor V (FV) gene and 20210 of the prothrombin (FII) gene have been associated with an increased risk of venous thromboembolism. We report a thrombosis-prone family in which one subject--the propositus who exhibited combined heterozygous FV G1691A and FII G20210A mutations--showed spontaneous and early clinical onset (at 23 years), recurrences of deep-vein thrombosis and pulmonary embolism. His asymptomatic father carried the FII G20210A substitution and his mother, characterized by an isolated thrombotic episode on occasion of surgery (at 48 years), carried the FV G1691A substitution. In the maternal lineage, one of the propositus' uncles had thrombosis on occasion of a bone fracture (at 65 years) despite the absence of known prothrombotic defects. A sister of the propositus carried the FII G20210A and the brother the FV G1691A mutation. They have been asymptomatic until now. The propositus' two children, 20 and 16 years old, both carry the FV G1691A substitution and have been asymptomatic until now. The plasma levels of FII were higher in carriers of the FII G20210A allele if compared with noncarriers, and the activated protein C resistance phenotype, associated with the FV Leiden mutation, showed a complete correlation with the FV G1691A mutation. Despite the very limited number of thrombotic cases involved in this survey, which does not allow statistically sound conclusions, the data obtained from this family suggest that the synergy of inherited factors and transient risk conditions could play a key role in the occurrence of thrombotic accidents.     

Prevalence of factor V Leiden and prothrombin 20210 A variant in Bulgarian patients with pulmonary thromboembolism and deep venous thrombosis.

Factor V Leiden mutation and prothrombin variant 20210 A are well-known risk factors for venous thrombosis (DVT). Recent papers have reported a lower prevalence of factor V Leiden in patients with pulmonary thromboembolism (PTE) than in patients with deep venous thrombosis. The aim of the present study was to compare the prevalence of factor V Leiden and the prothrombin 20210 G <-- A mutation in patients with DVT and in patients with PTE. We studied 128 consecutive patients (45 with DVT, 40 with PTE, and 43 with DVT and PTE) for factor V Leiden and prothrombin 20210 A. One hundred healthy persons matched by age and sex were used as controls. Factor V Leiden was present in five of the patients with PTE [12.5%; 95% confidence interval (CI), 1.5-23.5%; not significant], 15 of the patients with DVT (33.3%; 95% CI, 9.6-38.7%; P < 0.001), and 12 of the patients with DVT and PTE (27.9%; 95% CI, 4.8-33%; P = 0.001). Results for the prothrombin 20210 A mutation were as follows: four of 40 patients with PTE (10%; 95% CI, 0-13.3%; P = 0.46), nine of 45 (20%) of the patients with DVT (95% CI, 0.5-25.5%; P < 0.05) and eight of 43 with DVT and PTE were heterozygous (18.6%; 95% CI, 0-23.9%; P = 0.02). In conclusion, there is a significantly higher frequency of factor V Leiden among patients with DVT than in patients with PTE. However, there is no significant difference of factor V Leiden or 20210 A prothrombin mutation in patients with DVT than in patients with combined DVT/PTE, therefore patients with DVT, carriers of the mutations, do not appear to be at lower risk for pulmonary embolism.     

Coagulation factors II, V, VII, and X, prothrombin gene 20210G-->A transition, and factor V Leiden in coronary artery disease: high factor V clotting activity is an independent risk factor for myocardial infarction

Increased levels of hemostatic factors and genetic mutations of proteins involved in coagulation may play a role in the pathogenesis of coronary artery disease. We investigated clotting activity of factors II (FII:C), V (FV:C), VII (FVII:C), and X (FX:C), the prothrombin gene 20210G-->A transition, and the factor V Leiden mutation in 200 survivors of myocardial infarction and in 100 healthy controls. FV:C (P<0.0001) and FVII:C (P<0.0001) were found to be independent risk factors for myocardial infarction. High FV:C or high FVII:C combined with smoking or arterial hypertension increased the relative risk for myocardial infarction up to 50-fold. One of 177 patients (0.6%) and 4 of 89 controls (4.5%) had the prothrombin 20210 AG genotype. Eleven of 177 patients (6.2%) and 6 of 89 controls (6.7%) were heterozygous for the factor V Leiden mutation. No homozygous carrier for these mutations was found. Neither the prothrombin gene 20210G-->A transition (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01 to 1.1) nor the factor V Leiden mutation (OR, 1.0; 95% CI, 0.4 to 2.8) were associated with an increased relative risk for myocardial infarction. In conclusion, our data indicate that neither the prothrombin gene 20210G-->A transition nor the factor V Leiden mutation are risk factors for myocardial infarction. High FVII:C was confirmed to be an independent risk factor for myocardial infarction. Moreover, we describe for the first time that high FV:C is an independent risk factor for myocardial infarction.     

Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis.

Frequently an inherited predisposition to thrombosis remains clinically silent until an additional environmental factor intervenes. The present study aimed to assess distribution of inherited risk factors of venous thrombosis in patients with venous thromboembolism (VTE). The prevalences of factor V Leiden (FV Leiden), prothrombin factor II G20210A (FII G20210A), C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR) mutations were studied in 149 VTE patients and 100 controls. The following key risks were established: previous deep venous thrombosis or pulmonary embolism (23.5%), bed rest (34.2%), immobilisation of lower limb (10.1%), hospitalisation (30.9%) and obesity (28.9%). In 29 (19%) patients and in three (3%) controls FV Leiden was found. A significant association between VTE and FV Leiden was established. There were six (4%) carriers of the FII G20210A among VTE patients and one in the controls. No associations between VTE and MTHFR polymorphisms (C677T, A1298C) were found. In three of 149 patients both FV Leiden and FII G20210A polymorphisms were observed. The mean protein C activity was slightly, though nonsignificantly, smaller in VTE patients. In conclusion, there was a positive association between venous thromboembolism and factor V Leiden. Only a weak trend favouring a relationship between prothrombin factor II G20210A and venous thrombolism was present. No associations between common polymorphisms of methylenetetrahydrofolate reductase and venous thromboembolism were found.     

Inherited thrombophilic risk factors in a large cohort of individuals referred to Italian thrombophilia centers: distinct roles in different clinical settings.

BACKGROUND AND OBJECTIVES: Despite inherited thrombophilic risk factors being strongly associated with vein thrombosis, decisions on whether to screen subjects for these factors vary in different clinical settings. DESIGN AND METHODS: We calculated the prevalence of inherited thrombophilic risk factors in a large cohort of patients (n=1,238) with different clinical manifestations of vein thromboembolism. In the present cohort, screening for inherited thrombophilia was worthwhile among patients who developed vein thrombosis of the leg or cerebral vein thrombosis. Carriers of FV Leiden or FII A(20210) mutation more frequently had had deep vein thrombosis of the leg (OR: 4.35; 95% CI: 3.39-5.60), superficial vein thrombosis (OR: 3.34; 95% CI: 2.06-5.41), or cerebral vein thrombosis (OR: 2.77; 95% CI: 1.10-6.96). RESULTS: The screening program appeared to have a limited relevance in patients with isolated pulmonary embolism (OR: 2.13; 95% CI: 1.28-3.54), or mesenteric vein thrombosis (OR: 2.05; 95% CI: 1.22-3.44). INTERPRETATION AND CONCLUSIONS: The lack of association with inherited thrombophilia does not justify routine screening of patients with thrombosis of the upper extremities or with retinal vein thrombosis.     

Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3'-untranslated region of the prothrombin gene

The odds ratio for the FII 20210G/A mutation in 504 patients with venous thromboembolism compared to controls was 2.0 (95% CI 1.0–4.0) and, for factor V Leiden, 5.8 (95% CI 3.3–10.3). 3/504 patients were heterozygous for both mutations. None of the patients had combined natural anticoagulant deficiency and the FII 20210G/A mutation. We conclude that the FII 20210G/A mutation is present in 2.6% of the population and the relative risk of venous thromboembolism in carriers is 2.0.     

Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients.

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction-based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases.     

The impact of heterozygosity for the factor V Leiden and factor II G20210A mutations on the risk of thrombosis in Greek patients.

AIM: There is growing evidence that a number of genetic risk factors predispose independently to venous thrombosis and the coexistence of defective genes is involved in the manifestation and recurrence of thrombotic events. The goal of this study was to examine the efficiency of the selection criteria for performing a genetic test for the factor V G1691A (Leiden) and factor II G20210A mutations. METHODS: Blood samples were drawn from 119 patients referred to us by their physicians. FV and prothrombin (FII) mutations were detected by polymerase chain reaction (PCR) followed by digestion with restriction endonucleases MnlI (FV), HindIII and MspI (FII). RESULTS: Patient carrier frequencies were 16.8% and 10.08% for FV Leiden and FII G20210A, respectively. Heterozygosity for FII G20210A was observed in 10.0% of FV Leiden carriers whereas FV Leiden homozygosity was noted in 1.68% of the patients. Genotype frequencies were in conformity with Hardy-Weinberg equilibrium by the chi square goodness of fit test. CONCLUSION: The obtained data provided a substantial genetic explanation of the thrombotic phenotype in approximately 25% of the patients and thus the physicians selection criteria were sufficient for genetic testing. Furthermore, coinheritance of both genetic defects were significantly associated with increased thrombosis risk and that of recurrent thrombosis.     

FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian population

The absolute rate of recurrence of venous thromboembolism (VTE) is approximately 5% per year. There is a lower rate of recurrence in provoked VTE, and higher in idiopathic one. So far, there is no consensus whether hereditary thrombophilia should be considered as a persistent risk factor, and whether it requires long-term anticoagulant therapy. The aim of our study was to estimate the risk of recurrent VTE in patients carrying FV Leiden mutation in Serbian population.In retrospective study (1994-2006), we have evaluated the risk of recurrent VTE in 56 patients who are carriers of FV Leiden mutation, in comparison to group consisting of 56 patients non-carriers of FV Leiden mutation. Patients with FII G20210A and MTHFR C677T mutations, antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, malignancies and diabetes were excluded from the study.Recurrent VTE occurred in 44.6% of the patients, carriers of the FV Leiden mutations, vs. 26.7% in non-carriers group (P<0.05). The incidence rate was 3.7 and 2.2% per year, respectively. The estimated relative risk of recurrence for FV Leiden carriers was 1.67 (95% CI 0.99-2.81, P=0.049). The 60% of patients with mutation and only 13% without mutation develop rethrombosis during first year after discontinuance of therapy (P<0.01).In our study patients with symptomatic VTE who are carriers of the FV Leiden gene mutations have a higher risk of recurrent VTE than non-carriers. Our data suggest the importance of the FV Leiden mutation detection and the estimation of the clinical condition for successful secondary prophylaxis of VTE.     

Familial thrombophilia and the occurrence of fetal growth restriction

BACKGROUND AND OBJECTIVES: To evaluate the association between unexplained or gestational-hypertension-associated fetal growth restriction (FGR) and factor V Leiden, prothrombin A20210 mutations, and methylenetetrahydrofolate reductase (MTHFR) TT 677 genotype. DESIGN AND METHODS: Sixty-one women with a previous history of FGR and 93 parous women with uneventful pregnancies from the same ethnic background were investigated for the presence of factor V (FV) Leiden, prothrombin A20210 mutations, and MTHFR TT 677 genotype. Moreover, antiphospholipid antibodies, antithrombin, protein C, and total and free protein S antigen were determined in all patients. RESULTS: Among the controls, 2 (2.2%) carried the FV Leiden mutation, 19 (20.4%) were TT MTHFR homozygotes and 1 (1.6%) carried the prothrombin A20210 allele. The FV Leiden mutation was present in 8 women with FGR (13.1%, OR: 6.9, 95%CI 1.4-33.5), the TT MTHFR homozygosity in 17 (27.8%, OR: 1.5, 95%CI 0.7-3.2) and the A20210 prothrombin allele in 7 (11.5%, OR: 5.9, 95%CI 1.2-29.4). In six cases (9.8%) there was coexistence of more than one mutation (2 had the FV Leiden and the TT MTHFR genotype and 4 carried the A20210 prothrombin allele and TT MTHFR genotype). A logistic regression analysis showed that FV Leiden and A20210 prothrombin mutations were independently associated with the occurrence of FGR. INTERPRETATION AND CONCLUSIONS: Present data indicate an association between prothrombotic genetic factors and FGR.     

Impact of Thrombophilic Genetic Factors on Pulmonary Embolism: Early Onset and Recurrent Incidences

The importance of genetic thrombophilic factors in the development of venous thromboembolism has been increasingly recognized. Factor V Leiden (FVL), prothrombin gene mutation G20210A (FII G20210), genetic variant C677T of the methylentetrahydrofolate reductase (MTHFR), as well as the polymorphism A2 (PlA2) in platelet glycoprotein IIb/IIIa were recently discussed. We analyzed the contribution of genetic thrombophilic factors to the pathogenesis of pulmonary embolism (PE) and their association with the early onset and recurrence of PE using DNA analysis methods. In this case control trial we found thrombophilic genetic variants in 58.8% of 51 patients with PE. FVL was found in 23.5% of the patients versus 7.1% of the 98 controls (p = 0.01), PlA2 IIb/IIIa was found in 35.3% vs. 14.3% (p = 0.03), and FII G20210A was found in 5.9% vs. 2.0% (NS). Patients with recurrent PE had a very high prevalence of genetic factors, 70.4%. High prevalence of FVL was found in patients under 45 years of age: 39.3% (OR = 14.23, 95% CI = 1.58–330.03, p = 0.01) as well as in patients with recurrent incidence (37%, OR = 7.647, 95% CI = 2.27–26.44, p = 0.001). FVL was also significantly higher in the subgroup of patients with PE combined with deep venous thrombosis (OR = 6.500, 95% CI = 1.81–23.76, p = 0.002) in comparison with patients with isolated PE (OR = 2.261, 95% CI = 0.50–9.69). The carriers of FVL are at higher risk for early and recurrent PE events. High prevalence of PlA2 in PE patients evidently shows the impact of this polymorphism in PE development. A different treatment should be considered in carriers of thrombophilic defects.     

Effects of factor V gene G1691A, methylenetetrahydrofolate reductase gene C677T, and prothombin gene G20210A mutations on deep venous thrombogenesis in Behçet's disease

OBJECTIVE: Beh?et's disease (BD) is a multisystemic disease of unknown etiology, characterized by aphthous ulcerations and uveitis, that is common in the Turkish population. Venous involvement is observed in 25% of the cases. While superficial thrombophlebitis is the most common finding, deep venous thrombosis (DVT) follows it. Hyperactivity in the coagulation pathway, hypoactive anticoagulation mechanisms, or faulty fibrinolysis generate a tendency for thrombogenesis. Mutations of the genes involved in these pathways may cause predisposition to thrombosis. METHODS: Possible roles of methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A (Leiden), and prothrombin gene G20210A polymorphisms in venous thrombogenesis were evaluated in patients with BD; 100 healthy people, 30 BD patients without DVT, 30 BD patients with DVT, and 30 patients with idiopathic DVT were studied with the restriction fragment length polymorphism method for these 3 polymorphisms. The frequencies of these mutations for each group, separately and in combinations, are described. RESULTS: Among the 3 mutations, FV Leiden mutation was found to be a risk factor for DVT. An association between FV Leiden mutation and BD was likely, but FV Leiden mutation did not increase the risk for deep venous thrombogenesis in BD patients. MTHFR gene C677T mutation does not increase risk of DVT in BD either alone or combined with FV Leiden mutation. CONCLUSION: Although a thrombotic tendency is one of the major characteristics of BD, we found no association between these 3 thrombogenetic mutations and BD patients with thromboses.     

Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran

BACKGROUND: The mutation in factor V (FV) G1691A, known as factor V Leiden, and prothrombin (FII) gene G20210A are the two most prevalent causes of inherited thrombophilia. The present study reports the prevalence of factor V Leiden and the prothrombin G20210A gene mutations among healthy individuals of Kurdish ethnic background in Western Iran. METHODS: Four hundred thirty-four healthy unrelated individuals, 255 male and 179 female, with a mean age of 28.7+/-15.5 from the Kermanshah Province of Iran were studied for prothrombin G20210A mutation. The factor V Leiden mutation was studied in 404 healthy individuals, of whom 232 were male and 172 were female. The factor V Leiden and prothrombin G20210A were detected by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method using Mnl I and Hind III restriction enzymes, respectively. RESULTS: Among 434 individuals studied for prothrombin G20210A mutation seven carried this mutation as heterozygous (four female subjects and three male), giving a prevalence of 1.6% [95% confidence intervals (CI) 0.5-2.7) and an allele frequency of 0.8%. No homozygous prothrombin 20210AA was found. Factor V G1691A mutation was detected as heterozygous in 11 of 404 healthy individuals (five female and six male) and as homozygous in one male indicating a prevalence of 2.97% (95% CI 1.3-4.6) and allele frequency of 1.6%. CONCLUSIONS: Our results indicated that the factor V Leiden and prothrombin G20210A mutations are not rare among populations of Western Iran and that the relationship between venous thrombophilia and these mutations have to be further studied in Western Iran population, which, in turn, may suggest a causal effect.     

Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism

Venous thromboembolism (VTE) is a common vascular disease that results in two major clinical manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Several genetic risk factors, especially factor V Leiden and prothrombin G20210A mutations have been reported to be related to VTE in Caucasians, but the relationship remains controversial in other populations. Thus, the objective of the present study was to compare the frequency of the two mutations and also to investigate whether acquired risk factors other than genetic mutations may play a different role in Chinese VTE patients. Thirty-five patients were diagnosed with DVT concomitant PE, 178 patients with DVT, 54 patients with PE and 102 control subjects were recruited. The mutation was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Of all subjects, none was a carrier of factor V Leiden or prothrombin G20210A mutations. The frequency of surgery was significantly higher in the PE group than that in other groups. There was no significant difference among the three groups in other known risk factors. The data presented here indicate that factor V Leiden and prothrombin G20210A mutations are very rare in the Chinese population, and the genetic risk profile of VTE in the Chinese population is different from that in Caucasians.     

Prothrombin G20210A gene mutation and further prothrombotic risk factors in childhood thrombophilia.

Risk factors for venous thrombosis in adults are the prothrombin G20210A and the factor V (FV) G1691A mutations and hereditary deficiencies of protein C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We therefore investigated 261 patients aged 0 to 18 (median 5.7 years, 48% male) with venous thrombosis and controls (n=370) for the presence of prothrombotic risk factors including the prothrombin G20210A mutation. The following frequencies of hereditary risk factors (patients versus controls), odds ratios (OR) and 95% confidence intervals (CI), or results of Fisher's exact test, respectively, were found: prothrombin G20210A, 4.2% versus 1.1%, OR/CI 4.1/1.3 to 12.8; FV G1691A, 31.8% versus 4. 1%, OR/CI 11.0/6.2 to 19.7; protein C deficiency, 9.2% versus 0.8%, OR/CI 12.4/3.7 to 41.6, protein S deficiency, 5.7% versus 0.8%, OR/CI 7.5/2.1 to 26.0; antithrombin deficiency in 3.4% in the patients, but not in the controls, P=0.0003. The prothrombin mutation was combined with the heterozygous FV G1691A mutation (2. 3%) or protein C deficiency (0.3%) in the patients, but not in the controls (prothrombin and FV mutation, P=0.0048; prothrombin and protein C deficiency, not significant). The carrier frequencies and ORs of all hereditary risk factors showed a non-significant trend toward higher prevalences in patients suffering spontaneous thrombosis, compared with those with an additional underlying disease. In conclusion, the prothrombin G20210A and the FV G1691A mutation, deficiencies of protein C, protein S, and antithrombin are important risk factors for venous thrombosis during childhood and adolescence.     

The thrombophilic pattern of different clinical manifestations of venous thromboembolism: a survey of 443 cases of venous thromboembolism

Although pulmonary embolism (PE) and deep vein thrombosis (DVT) share many risk factors, it is uncertain whether thrombophilic abnormalities may impact differently on the development of these two clinical manifestations of venous thromboembolism (VTE). To give further insight into this issue, we estimated the association of PE with different types of thrombophilia and evaluated whether these abnormalities have a different prevalence in patients presenting with PE, alone or associated with DVT, as compared with those with isolated DVT. In this study 443 consecutive patients with a first episode of VTE and 304 matched healthy controls underwent laboratory screening for thrombophilia, including natural anticoagulants, factor V Leiden and prothrombin G20210A polymorphisms, antiphospholipid antibodies, homocysteine, factor VIII, and lipoprotein(a). Of the 443 patients, 224 patients had isolated DVT, 144 had combined DVT/PE, and 75 had isolated PE. At least one thrombophilic abnormality was detected in 72.8% of DVT, 66% of DVT/EP, and 60% of isolated PE patients. A high prevalence of hyperhomocysteinemia and elevated lipoprotein(a) levels was found in all patients with no significant differences among the three groups. The prevalence of prothrombin G20210A polymorphism and of elevated factor VIII levels was significantly higher in patients with DVT and DVT/PE than in controls, but not in those with isolated PE, whereas factor V Leiden polymorphism was associated with isolated DVT but not with DVT/PE or isolated PE. In conclusion, the thrombophilic burden seems different in isolated PE versus DVT with or without PE, suggesting that PE may encompass a different pathophysiological process of thrombosis to DVT.