Factor V Leiden G1691A, prothrombin G20210A, and MTHFR C677T mutations in Turkish inflammatory bowel disease patients

BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) have an increased risk for thromboembolic complications. We investigated the incidence of factor V Leiden G1691A, methylene tetrahydrofolate reductase (MTHFR) C677T, and prothrombin G20210A mutation in 27 Turkish IBD patients with no history of thromboembolic disease. METHODOLOGY: Twenty-seven patients, 22 with ulcerative colitis (UC) and 5 with Crohn's disease (CD), and 47 healthy were included to the study. The DNAs were obtained from peripheral blood by using pure polymerase chain kit. Then, factor V Leiden G1691A, which active protein C resistance positive, prothrombin G20210A and MTHFR C677T mutations were investigated in DNA by using LightCycler-Factor V Leiden G1691A mutation, Prothrombin G20210A and MTHFR C677T estimate kits. RESULTS: The heterozygote factor V Leiden G1691A mutation was detected in 3 (11.1%) patients with IBD and 2 (4.3%) controls (p > 0.05). The homozygote factor V Leiden G1691A mutation was not estimated among patients and controls. Heterozygote prothrombin G20210A mutation was detected in 2 (7.4%) patients with IBD and in 0 (0%) controls (p > 0.05). There was no homozygote prothrombin G20210A mutation in IBD and controls. Heterozygote MTHFR C677T mutation was 10 of 27 (37%) patients with IBD while 15 of 47 (32%) controls (p > 0.05). Homozygote MTHFR C677T mutation was detected in 4 patients (14.9%) with IBD and 3 (6.3%) controls (p > 0.05). CONCLUSIONS: Our study did not reveal any association between IBD and the most common hereditary thrombophilic factors and these mutations interfere with neither disease manifestations nor the thrombotic complications.     

Factor V Leiden, prothrombin G20210A and MTHFR gene mutations in inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) gene mutations in IBD patients followed in our outpatient clinic. METHODS: Thirty-four patients with ulcerative colitis and 28 patients with Crohn's disease and 80 healthy controls were included in the study. No patient had a history of previous thromboembolism. Factor V Leiden, prothrombin G20210A and MTHFR gene mutations were studied. RESULTS: Heterozygote factor V Leiden mutation was found in five (6.25%) control patients and in two (3.2%) IBD patients. Heterozygote MTHFR mutation was obtained in seven (11.3%) IBD patients and in five (6.25%) controls. Heterozygote prothrombin G20210A mutation was found in two (2.5%) and homozygote MTHFR mutation in one (1.25%) control patient. There was no statistical difference between the IBD group and healthy controls. CONCLUSIONS: Genetic mutations that could increase the thrombosis risk were not found to be different in IBD versus the normal population in our study.     

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 (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.     

An investigation of the association of the prothrombin G20210A gene mutation and inflammatory bowel disease: Factor II and IBD

BACKGROUND: A thrombotic etiology for inflammatory bowel disease (IBD) has been proposed as a result of its association with thromboembolic complications, smoking, the oral contraceptive pill, and the response of ulcerative colitis (UC) patients to heparin. We have previously demonstrated an increased prevalence of the Factor V Leiden mutation in UC and wished to investigate the frequency of the recently discovered prothrombin G20210A gene mutation in IBD. The aim of the study was to investigate the hypothesis that the prothrombic state associated with the prothrombin G20210A gene mutation is involved in the etiology of IBD. PATIENTS AND METHODS: A prospective cohort study of patients attending the Bristol Royal Infirmary and Gloucestershire Royal Hospital's IBD clinics was performed. Thirty-nine patients with IBD (24 with Crohn's disease and 15 with UC) and 100 historical controls were screened for the presence of the prothrombin gene mutation using a heteroduplex-based polymerase chain reaction technique. None of the patients with IBD had a personal history of thromboembolism, while three of them had a family history. RESULTS: No IBD patients had the prothrombin gene mutation compared with four (4%) controls (allelic frequency 2%). CONCLUSION: There does not appear to be an association of the prothrombin gene mutation with IBD and therefore it is unlikely to be involved in the etiology of IBD.     

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.     

Role of acquired and hereditary thrombotic risk factors in colon ischemia of ambulatory patients

BACKGROUND & AIMS: Hypercoagulable states may play an important role in the pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis investigating the role of acquired and hereditary thrombotic risk factors in patients with definite diagnosis of colon ischemia. METHODS: We compared the frequency of antiphospholipid antibodies, protein C, protein S, and antithrombin deficiencies, factor V Leiden, prothrombin gene mutation G20210GA, and methylenetetrahydrofolate reductase C677T in 36 patients (23 men, 13 women; mean age, 64.8 years) with colon ischemia, 18 patients with diverticulitis, and 52 healthy controls. RESULTS: The prevalence of antiphospholipid antibodies was significantly higher in patients with colon ischemia compared with inflammatory and healthy controls (19.4% vs. 0% and 1.9%). Among genetic factors, only factor V Leiden was significantly associated with colon ischemia (22.2% vs. 0% and 3.8%). A combination of thrombophilic disorders was found in 25% of the cases. Overall, one or several prothrombotic abnormalities were present in 26 patients (72%). CONCLUSIONS: A comprehensive thrombophilic screening in colon ischemia reveals a congenital or acquired thrombophilic state in 72% of patients. Hereditary and acquired thrombotic risk factors may play an important role in the disease pathogenesis.     

Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR G677A among 594 thrombotic Jordanian patients.

Venous thromboembolism develops as the result of multiple interactions between non-genetic and genetic risk factors. In order to estimate the frequency of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in Jordanian thrombotic patients, we studied 594 patients admitted to the King Hussein Medical Center for thrombophilia assessment. Polymerase chain reaction detected 25.7% (20.7% heterozygous, 5% homozygous), 6% (5.8% heterozygous, 0.2% homozygous) and 31.7% (25% heterozygous, 6.7% homozygous) for factor V Leiden, prothrombin G20210A and MTHFR C677T mutations, respectively. A one-stage clotting assay was used to measure prothrombin activity. None of the prothrombin G20210A mutant patients had high prothrombin activity. The high prevalence found among our study group of factor V Leiden and prothrombin G20210A confirms the importance of thrombophilia screening for patients with venous thrombosis with family history and those with additional risk factors. On the contrary, the high prevalence of the MTHFR C677T mutation among arterial thrombosis patients shows its importance in screening in arterial thrombosis patients. These results, which are close to the prevalence found by other studies in the region, suggests that the Eastern Mediterranean region is probably the area of origin of these mutations, especially factor V Leiden. The knowledge of these frequencies in the Middle East region through population-based studies will contribute to a better understanding of the interaction between genetic and environmental risk factors underlying the mentioned mutations.     

Factor V Leiden mutation and PAI-1 gene 4G/5G genotype in thrombotic patients with Behcet's disease.

Behcet's disease is a chronic systemic vasculitis with particular systemic features including thrombotic events. The present study was designed to analyse the role of the factor V Leiden and the prothrombin G20210A mutations and plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk of patients with Behcet's disease. A total of 50 unrelated patients with Behcet's disease (34 male, 16 female) were the subjects of the study. Twenty-seven of 50 patients with a history of thrombosis comprised group 1, and 23 patients with no thrombosis comprised group 2. In group 1, nine of the 27 patients (33%) were found to have the factor V Leiden mutation (7.1% in healthy population), and the 4G/4G genotype was found in 23% of the patients (26% in control). No patient had the prothrombin G20210A mutation (2.2% in healthy control). In group 2, two patients (9%) had the factor V Leiden and one patient (4%) had the prothrombin G20210A mutations. The 4G/4G polymorphism was found in 30.5% of the patients. The differences in the frequencies of factor V Leiden mutation between group 1 and group 2 (odds ratio, 5.3; 95% confidence interval, 1.0-27.5) and between group 1 and the healthy population were statistically significant ( 0.05). No statistically significant association was found for the prothrombin G20210A mutation and the 4G/5G genotype between the two groups or between each group and the healthy population, indicating that the prothrombin G20210A mutation and the 4G/4G polymorphism do not play a role in the development of thrombosis in Behcet's disease. These data suggested that the factor V Leiden mutation might be a risk factor for the development of thrombosis in Behcet's disease patients.     

Survey of factor V leiden and prothrombin gene mutations in systemic lupus erythematosus

The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G→A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher’s exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99–133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial. Received: 1 August 2000 / Accepted: 9 March 2001     

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.     

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.     

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.     

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.     

Ramifications of four concurrent thrombophilic mutations and one hypofibrinolytic mutation.

A kindred was examined in which the 48-year-old white female proband with three deep venous thrombosis-pulmonary emboli events had four thrombophilic and one hypofibrinolytic mutations, and in which her 14-year-old asymptomatic daughter had four thrombophilic mutations. The proband was heterozygous for the G1691A factor V Leiden, G20210A prothrombin, and platelet glycoprotein IIIa PL A1/A2 mutations, had high factor VIII (221%), and was homozygous for the 4G4G plasminogen activator inhibitor-1 gene mutation, with high plasminogen activator inhibitor activity (23.7 U/mL). Her 14-year-old daughter was homozygous for the G1691A factor V Leiden and platelet glycoprotein IIb-IIIa PL A2/A2 mutations, compound heterozygous for the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) mutations, and heterozygous for the G20210A prothrombin mutation, a combination with an estimated likelihood of 1.6 x 10(-7). In 247 white healthy controls, there was no V Leiden homozygosity and no V Leiden-prothrombin gene compound heterozygosity. Heterozygosity for the V Leiden and prothrombin gene mutations was 3.2% and 4.1%, respectively. Homozygosity for the platelet glycoprotein IIb-IIIa PL A2A2, PAI-1 gene 4G4G, and C677T MTHFR mutations was 3.2%, 22.7%, and 12%, respectively. The proband will receive anticoagulation therapy for life. Beyond aspirin, avoidance of exogenous estrogens, and enoxaparin prophylaxis during pregnancy, it is not known whether the proband's daughter should have lifelong anticoagulation therapy, or only after her first thrombotic event.     

Cerebral-vein thrombosis: retrospective study of twenty seven cases

PURPOSE: Among the locations of venous thrombosis, even if rare, cerebral-vein thrombosis is a severe event with a high mortality rate. No aetiology is found in 20 to 30% of the cases. In recent years, inherited coagulation disorders have been described, as risk factors for venous thrombosis. We report the results of a retrospective study of 27 patients who suffered cerebral-vein thrombosis, in which coagulation abnormalities have been searched for. METHOD: The patients were referred to the haemostasis laboratory of the Henri Mondor hospital between august 1982 and June 1988, after a cerebral-vein thrombosis. The predisposing factors, personal and family history of thromboembolism, clinical presentation, thrombosis location, evolution under treatment and long-term outcome, have been noted. Deficiencies in antithrombine, protein C, protein S, the Factor V Leiden and the G20210A prothrombin-gene mutation, the presence of lupus anticoagulant, of anticardiolipin antibodies as well as a hyperhomocysteinaemia have been searched, either at the initial presentation, or a posteriori. RESULTS: Fourty-one percent of patients had a coagulation abnormality. The prevalence of the different abnormalities was: inherited deficiency in AT 7.4%, in PC 8%, in PS 12.5%, factor V Leiden mutation 12%, G20210A prothrombin-gene mutation 12%. Two patients had combined defects: AT and PC deficiency in one, F V Leiden and F II G20210A mutations in one. e of the patient had lupus anticoagulant. Three patients had a significant rate of anticardiolipin antibodies. Five patients out of eight displayed a moderate hyperhomocysteinaemia. Nothing (past history, age, predisposing factors) distinguished those patients bearing a coagulation disorder from the others. The venous thromboembolic relapse rate of 15 % (4/27 patients). Three of them had an inherited thrombophilic abnormality. CONCLUSION: We recommend an investigation of the haemostasis after every cerebral venous thrombosis.     

Prothrombotic gene mutations and Crohn's disease; is there any association?

BACKGROUND/AIMS: Patients with inflammatory bowel disease have an increased tendency for thromboembolism. In this study we aimed to determine the frequency of FV gene and Prothrombin G20210A gene mutations in a group of patients with Crohn's Disease (CD) and estimate its correlation with disease activity and clinical subtype. METHODOLOGY: Forty-four CD patients and 43 healthy controls were included in the study. Twenty-three of the patients had inflammatory CD, while 11 had fibrostenotic and 10 had fistulizing CD. Only one patient had a history of deep vein thrombosis. Polymorphism Light Cycler FV Leiden mutation detection kit and Light Cycler prothrombin (G20210A) mutation detection kit were used for the detection of mutations in DNA samples. RESULTS: Forty of the CD patients had normal factor V genotype, three (6.8%) patients showed a heterozygous, and one (2.3%) patient homozygous pattern. Two (4.7%) of the 43 controls showed heterozygous factor V mutation and 41 had normal FV genotype. Two (4.6%) CD patients had heterozygous prothrombin G20210A mutation, and there was only one (2.3%) homozygous mutation in the control group. There was no significant difference between controls and CD patients neither for factor V mutation (p > 0.05) nor for prothrombin G20210A mutations (p > 0.05). No correlation was found between disease activity and both gene mutations (p > 0.05), as well as between disease subtype and gene mutations (p > 0.05). CONCLUSIONS: The prevalence of prothrombin G20210A gene and factor V Leiden gene mutations were found to be statistically insignificant among CD patients and control group.     

Prevalence of genetic prothrombotic factors (factor V Leiden and II20210 prothrombin mutation) in glomerular nephropathies with or without thrombosis

The presence of genetic prothrombotic factors (factor V Leiden and the prothrombin II20210 mutation) was investigated in 38 patients with glomerulonephritis with or without a history of thrombotic events and/or nephrotic syndrome. We found an increased prevalence (36%) of heterozygous factor V Leiden in those patients with a history of thrombotic events. This is ten times the prevalence in the normal Spanish population. Carrier status for this mutation may be a determining factor in the development of thrombotic events along with the acquired disorders of coagulation to which these patients are prone. We found only one patient who was a carrier of the G-A II20210 mutation of the prothrombin gene; this patient had no history of venous thrombosis or embolism. Our findings suggest the need to measure activated protein C resistance and to look for the most frequent genotype causing it, Factor V Leiden, in patients with glomerulonephritis to identify those at risk who may benefit from prophylaxis against thrombosis.     

Deep vein thrombosis during enoxaparin prophylactic treatment in a young pregnant woman homozygous for factor V Leiden and heterozygous for the G127-->a mutation in the thrombomodulin gene.

Variability of thrombotic disease among individuals homozygous for factor V Leiden has been described. It has been shown that some thrombotic patients carry an additional genetic risk factor such as protein C, protein S, antithrombin deficiency or the G20210A mutation on the prothrombin gene. The occurrence of a deep vein thrombosis during enoxaparin prophylactic treatment in a pregnant woman homozygous for factor V Leiden, without other known prothrombotic genetic factors, led us to investigate her thrombomodulin gene. We found that the patient was heterozygous for the previously described G127-->A mutation, which results in an Ala25-->Thr substitution. Furthermore, for this patient, the allelic combination at the 1418 polymorphic site was C/T, which predicts an Ala455-->Val replacement. Although larger studies are required, this case report suggests that thrombomodulin gene mutations could be an additional genetic risk factor for thrombosis in carriers of the factor V Leiden mutation.     

Genetic risk factors of venous thromboembolism

Up to date several hereditary disorders have been identified as prothrombic risk factors. The most common inherited thrombotic disorders include activated protein C resistance (factor V Leiden), prothrombin G20210A mutation, hyperhomocysteinemia, deficiencies of protein C, protein S, antithrombin III, and thrombomodulin. This article focuses on the clinical and the laboratory aspects of some of the inherited venous thrombotic disorders including the factor V Leiden, prothrombin G20210A mutation and protein S deficiency.