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.     

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.     

Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism

STUDY OBJECTIVES: To investigate whether the FII A(20210) mutation is associated with isolated pulmonary embolism (PE). DESIGN: Case-control study. SETTING: Five thrombosis centers in southern Italy. PATIENTS: Six hundred forty-seven consecutive referred patients with objectively documented venous thrombosis and 1,329 control subjects. Measurements and results: Medical histories were collected. The G-to-A transition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to-A transition at nucleotide position 20210 within the prothrombin gene locus (FII A(20210)), levels of anticoagulant factors, and levels of antiphospholipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with additional PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% and 16.6%, respectively) and FII A(20210) mutation (14.2% and 12.6%, respectively), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, respectively). In both groups, the frequencies of FV Leiden and/or FII A(20210) mutation were higher than those observed among 1,329 apparently healthy control subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients with isolated PE (n = 126), prevalences of FV Leiden (7.1%) and FII A(20210) mutation (8.7%) were similar to those of control subjects. Inherited thrombophilic abnormalities were less frequent among patients with PE only (15.6%) than among those with DVT only (37.0%; p < 0.001) or whose conditions were complicated by PE (28. 0%; p = 0.020). Adjusting for age and sex, FV Leiden mutation, FII A(20210) mutation, or both mutations were associated with DVT with PE (FV Leiden mutation: odds ratio [OR], 3.0; 95% confidence interval [CI], 1.6 to 5.5; FII A(20210) mutation: OR, 2.6; 95% CI, 1. 3 to 5.2; and both mutations: OR, 82.1; 95% CI, 7.5 to 901.2) or without PE (FV Leiden mutation: OR, 6.1; 95% CI, 4.0 to 9.3; FII A(20210) mutation: OR, 2.8; 95% CI, 1.7 to 4.8; and both mutations: OR, 167.5; 95% CI, 21.6 to 1,297.7), but not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FII A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 22.1; 95% CI, 1. 3 to 370.2). CONCLUSIONS: FII A(20210) mutation is associated with DVT in the lower extremities alone or when complicated by PE, but it is not associated with isolated PE.     

Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years old with myocardial infarction

Several studies claim that prothrombin 20210GA and factor V Leiden mutations are related to arterial thrombosis. We investigated the frequencies of these mutations and their significance in the development of early atherosclerosis in acute myocardial infarction (AMI) patients younger than 55 years of age. We investigated 96 patients with AMI and 77 control subjects. The diagnosis of AMI was established by typical chest pain and ST elevations on the presentation electrocardiogram and characteristic cardiac enzyme elevations. None of the control subjects had evidence of cardiovascular disease. DNA samples were isolated from all subjects and prothrombin 20210GA and factor V Leiden mutations were determined by the RealTime PCR technique with the aid of a Light Cycler device. The prevalence of factor V Leiden mutation was 6.3% and 5.2% in the patient and control groups, respectively (OR 0.6 [95% CI 0.1- 3.9], P = 0.6), whereas the prevalence of prothrombin G20210A mutation was 4.2% and 2.6% in the patient and control groups, respectively (OR 2.8 [95% CI 0.2 - 32.2], P = 0.4). None of the patients had both mutations. Prothrombin 20210GA and factor V Leiden mutations are not significant risk factors for the development of myocardial infarction in patients less than 55 years old in Southern Turkey.     

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.     

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.     

Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis

OBJECTIVE: To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Beh?et's disease (BD). METHODS: Included were 118 consecutive Italian BD patients followed over a 3-year period (1997-1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms. RESULTS: Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis. CONCLUSIONS: The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3'-untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.     

Risk of recurrent venous thrombosis in patients with G20210A mutation in the prothrombin gene or factor V Leiden mutation.

The impact of the G20210A prothrombin mutation, factor V Leiden and 677T mutation of methylene tetrahydrofalate reductase (MTHFR) in recurrent deep venous thrombosis (DVT) is not so clear. We have prospectively monitored 259 patients following a first episode of DVT in order to determine which factors influence the development of a recurrent event. Several clinical and biological factors together with the genetic polymorphisms of factor V Leiden, G20210A prothrombin and 677T MTHFR were assessed. During a median follow-up of 786 patient-years, 27 patients (14%) developed one objective episode of recurrent venous thrombosis. The carriers of a double defect, homozygous or double heterozygous for factor V Leiden and G20210A, had an increased risk after a first episode of DVT, while patients who were isolated heterozygous for factor V Leiden or G20210 had a risk of recurrent DVT similar to patients who had neither mutation (annual incidence of 12.1, 3.1, 2.9 and 2.8%). The 677T MTHFR mutation alone or combined with hyperhomocysteinemia was not associated with an increased risk of recurrent events. The development of proximal DVT (P=0.01) and the presence of a double defect (P=0.01) were the only two risk factors independently associated with a high recurrence ratio in the multivariate analysis. Thus, the annual incidence of DVT recurrence in patients without any of these two risk factors was only 0.6% (95% confidence interval, 0.2-0.9). We have identified a group of patients with DVT but at very low risk of re-thrombosis in whom an extended secondary thromboprophylaxis should be carefully considered.     

Prevalence of the G1691A mutation in the factor V gene (factor V Leiden) and the G20210A prothrombin gene mutation in the Thai population

We investigated the prevalence of a genetic variation in the factor V gene (G1691A Leiden mutation) and the prothrombin gene (G20210A) using polymerase chain reaction techniques in samples from 500 normal Thai population and among 50 unselected Thai patients with an objectively confirmed history of deep venous thrombosis. The prevalence of factor V Leiden and the prothrombin G20210A gene mutation in a group of 500 healthy controls was 0.2% in both groups (allele frequency of 0.1%). Of the 50 adult patients studied, none was a carrier of factor V Leiden or the prothrombin G20210A gene mutation. Our findings confirm that the prevalence of factor V Leiden and prothrombin G20210A gene mutation is lower among Asians than Caucasians and that the distribution of factor V Leiden is similar to that of the prothrombin G20210A variant. The low prevalence of these two mutations can, at least in part, account for the lower frequency of deep venous thrombosis reported in the Thai population. Screening for factor V Leiden and prothrombin gene mutation is of limited benefit and may not be cost-effective in Thai patients with the first episode of deep venous thrombosis.     

Risk factors for thrombophilia in extrahepatic portal vein obstruction

Scant information exists on the role of thrombophilia in extrahepatic portal vein obstruction (EHPVO). We studied 65 patients with EHPVO, 500 with deep vein thrombosis (DVT) of the lower limbs, and 700 healthy controls referred for thrombophilia screening, including the search for gain-of-function mutations in genes encoding coagulation factor V (factor V Leiden) and prothrombin (prothrombin G20210A); antithrombin, protein C, and protein S deficiency; and hyperhomocysteinemia. At least one abnormality in the thrombophilia screening was found in 40% of patients with either EHPVO or lower limb DVT and in 13% of controls, for odds ratios of 4.0 (95% CI, 2.3-7.0) and 4.4 (95% CI, 3.3-5.9), respectively. Statistically significant associations with EHPVO were observed for the prothrombin G20210A mutation (odds ratio, 8.1; 95% CI, 3.8-17.5) and the deficiencies of antithrombin, protein C, or protein S taken together (odds ratio, 4.5; 95% CI, 1.1-18.0). The odds ratio for the prothrombin G20210A was approximately twice that for lower limb DVT. Patients with factor V Leiden had an odds ratio for EHPVO of 0.8 (95% CI, 0.1-6.4) and for lower limb DVT of 7.5 (95% CI, 4.4-13.0). The odds ratio for EHPVO in patients with hyperhomocysteinemia was 2.0 (95% CI, 0.9-4.9). At variance with lower limb DVT, oral contraceptive use was not associated with an increased risk of EHPVO. Myeloproliferative disorders were diagnosed in 35% of patients with EHPVO. In conclusion, the risk for EHPVO is increased in the presence of thrombophilia resulting from the prothrombin G20210A mutation and from the deficiencies of the naturally occurring anticoagulant proteins, but not from factor V Leiden.     

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.     

Lower contribution of factor V Leiden or G202104 mutations to ischemic stroke in patients with clinical risk factors: pair-matched case-control study.

It was suggested that factor V Leiden and prothrombin G20210A mutations increase the risk of ischemic stroke only in combination with clinical risk factors of arterial ischemic disease. In these studies the controls were derived from the general population, with fewer clinical risk factors, which might have produced biased results. The factor V Leiden and prothrombin G20210A mutations were examined by polymerase chain reaction technique in 120 ischemic stroke patients and 120 controls younger than 65 years of age. Each patient had his own control, tightly matched in clinical risk factors. The prevalences of factor V Leiden and prothrombin G20210A mutations in patients were 8.3% (P = 0.02) and 7.5% (P = 0.04), respectively, and 2.5% for controls for both mutations. All carriers were single heterozygotes. In patients, but not in controls, the carriers of either mutation were mostly women and with fewer clinical risk factors for arterial ischemic events. In particular, considering both mutations as a single coagulation deficit, their presence increased the likelihood of ischemic stroke (odds ratio [OR] = 3.6; 95% confidence interval [CI] 1.4-9.3), especially among women (OR = 4.6; 95% CI: 1.2-17.8), normotensive persons (OR = 9.2; 95% CI: 1.1-17.8) and those having normal cholesterol (OR = 5.9; 95% CI: 1.6-21.2) and triglyceride serum concentrations (OR = 4.3; 95% CI: 1.5-12.8). In the studied sample of adult North Mediterranean population younger than 65 years the prevalences of factor V Leiden and prothrombin G20210A mutations were greater in patients with ischemic stroke than in matched controls. Unlike in studies with unmatched controls, we observed an apparently negative interaction of these mutations with clinical risk factors.     

Thrombophilic mutations among Southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden

BACKGROUND: A hypercoagulable state in sickle cell disease (SCD) and beta thalassemia has been established and thrombosis is an important aspect of the clinical spectrum of sickle cell disease. In a case-control study, the prevalence of factor V Leiden and prothrombin G20210A mutations were investigated among SCD patients from Southern Iran. METHODS: Patients comprised 60 individuals with SCD; of them 35 were with sickle cell anemia (SS) including 21 males and 14 females aged 17.2+/-8.3 years, 15 were sickle cell trait (AS) consisted of nine males and six females aged 30+/-15.4 years and 10 were sickle/beta thalassemia (S/Thal) (three males and seven females) aged 24.6+/-10.4 years. The control group were 126 apparently healthy individuals (50 males and 76 females) aged 20.1+/-9.8 years. Genotyping was done by polymerase chain reaction restriction fragment-length polymorphism (PCR-RFLP) using Mnl I and Hind III for factor V Leiden and prothrombin G20210A, respectively. RESULTS: Heterozygous factor V Leiden mutation was found in five of 35 (14.3%) SS patients, two of 15 (13.3%) AS individuals, one (a sickle/beta-zero thalassemia patient with IVSII.1 G-->A mutation) of 10 S/Thal patients (10%), and two of 126 (1.6%) control subjects (P<0.05). However, only one AS individual (6.7%) was found to be a carrier for prothrombin G20210A compared to five of 126 (4%) healthy individuals. Adjusted logistic regression analysis for the effects of age and sex was performed and a significant association was found between factor V Leiden mutation and sickle cell anemia with odds ratios (OR) of 6.5 (95% confidence intervals [CI] 1.19-35.33, P=0.03) in SS patients. However, increased prevalence of the factor V Leiden in AS individuals and S/Thal patients was not statistically significant compared to controls (OR 3.84, 95% CI 0.49-29.9, P=0.19 and OR 3.77, 95% CI 0.31-45.9, P=0.29, respectively). CONCLUSIONS: Our findings indicate a significant correlation between factor V Leiden and sickle cell anemia among Iranian patients. Association between venous thrombophilia and factor V Leiden mutation in Iranians with sickle cell anemia should be further studied.     

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paúl, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR = 6.08, 95% CI = 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR = 12.56, 95% CI = 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia.     

Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis

Objective

To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD).

Methods

Included were 118 consecutive Italian BD patients followed over a 3‐year period (1997–1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele‐specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms.

Results

Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis.

Conclusions

The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3′‐untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.

     

Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos.

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), <1% and 51% (+/-5%, alpha = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients.     

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

We investigated whether there is an association between factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) and cerebral thromboembolism in a pediatric Argentinean population. From May 1992 to January 2002, 44 consecutive children with arterial ischemic stroke (AIS) and 23 children with cerebral sinovenous thrombosis (SVT) were prospectively studied at a single center. The prevalence of both mutations was compared with a 102 age-matched controls. In children with AIS, the frequencies (patients vs. controls), odds ratio (OR), and 95% confidence interval (95% CI) for the presence of FVL were as follows: 2.3% vs. 2%, OR/95% CI, 1.16/0.2 to 13.2; P value = 0.99. No cases of PT20210A were found in this group. In children with SVT, the frequencies (patients vs. controls), OR, and 95% CI were as follows: FVL (4.3% vs. 2%, OR/95% CI, 2.27/0.22 to 6.2; P value = 0.99) and PT20210A (4.3% vs. 1%; OR/95% CI, 4.6/0.3 to 76.3; P value = 0.3354). One child with PT20210A also had an inherited protein C deficiency. In 12 (18%) out of the 67 children with cerebral thromboembolism, without the aforementioned mutations, other prothrombotic disorders were detected. Although a multi-center prospective study with a large number of Argentinean pediatric patients is needed to obtain considerable evidence, no association between factor V Leiden and/or prothrombin gene G20210A mutation and cerebral thromboembolism was found in this pediatric series.     

Prevalence of factor V Leiden and prothrombin G20210A in patients with gastric cancer

AIM: To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrom-bin G20210A, in patients with gastric cancer. METHODS: One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects, comparable for age and sex, were investigated. Factor V Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR. RESULTS: Among the 121 cancer patients, factor V Leiden was found in 4 cases (GA genotype: 3.3%) and prothrombin G20210A in 10 cases (GA genotype: 8.3%). Of the 130 control subjects, factor V Leiden was detected in 6 cases (GA genotype: 4.6%) and prothrombin G20210A in 8 cases (GA genotype: 6.1%). No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor V Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects. CONCLUSION: Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.     

Prevalence of factor V Leiden and prothrombin variant G20210A in patients age <50 years with no significant stenoses at angiography three to four weeks after myocardial infarction

OBJECTIVES: We sought to determine the frequencies of factor V Leiden and prothrombin variant G20210A in patients age <50 years with no significant coronary stenoses three to four weeks after myocardial infarction (MI). BACKGROUND: Factor V Leiden and prothrombin variant G20210A occur frequently in patients with venous thromboembolism. However, the contribution of these mutations to the development of MI requires clarification. METHODS: The frequencies of factor V Leiden and prothrombin variant G20210A were determined in 41 patients age <50 years who had "normal" or "near normal" coronary arteries (no stenosis >50%) at angiography three to four weeks after MI (the study group) and compared with those in 114 patients who had at least one angiographic stenosis >50% after MI (the control group). Patients age > or =50 years with, or without, stenoses were also studied. RESULTS: The frequency of factor V Leiden was 14.6% in patients age <50 years in the study group compared with 3.6% in patients in the control group (odds ratio [OR] 4.7 [95% confidence interval (CI) 1.3-17.7], p = 0.02). The frequency of the prothrombin variant G20210A was 7.3% in the study group compared with 1.8% in the control group (OR 4.4 [95% CI 0.7-27.5], p = 0.12). One or both mutations were present in 8 of the 41 patients (19.5%) age <50 years in the study group compared with 6 of the 114 patients (5.5%) in the control group (OR 4.4 [95% CI 1.4-13.5], p = 0.01). In all 271 patients (irrespective of age) with normal arteries, the frequency of factor V Leiden was 11.7% (7/60) compared with 4.3% (9/211) in patients with at least one >50% stenosis (OR 2.9 [95% CI 1.1-8.3], p = 0.04), and the frequency of prothrombin variant G20210A was 6.7% (4/60) compared with 1.4% (3/211) (OR 4.9 [95% CI 1.1-22.8], p = 0.04), respectively. CONCLUSIONS: The frequencies of factor V Leiden and/or prothrombin variant G20210A are increased in patients age <50 years with normal or near normal coronary arteries after MI.     

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.