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.     

Factors V leiden and II 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis

PURPOSE: Factor V Leiden and factor II 20210A are inherited disorders of the clotting system that occur frequently in patients with deep vein thrombosis. We conducted this study to determine whether these factors are also common in patients with pulmonary embolism. SUBJECTS AND METHODS: We determined the prevalence of factor V Leiden and factor II 20210A in 773 consecutive patients with objectively documented symptomatic deep vein thrombosis or symptomatic pulmonary embolism, or with a combination of these disorders. RESULTS: Isolated symptomatic deep vein thrombosis occurred in 345 patients; isolated symptomatic pulmonary embolism occurred in 236; and both anomalies occurred in 192. Factor V Leiden was present in 21 (9%) of the patients with isolated symptomatic pulmonary embolism, in 30 (16%) with both manifestations, and in 63 (18%) with isolated symptomatic deep vein thrombosis (P = 0.007). Factor V Leiden was more common among patients with deep vein thrombosis (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2 to 3.7; P = 0.006) or both pulmonary embolism and deep vein thrombosis (OR = 1.8; 95% CI: 1.0 to 3.3; P = 0.07) than among patients with isolated pulmonary embolism. Factor V Leiden was less common in massive pulmonary embolism (5% [7 of 127]) than in submassive pulmonary embolism (13% [21 of 155], P = 0.03). We found no significant difference in the prevalence of factor II 20210A among the three groups. CONCLUSION: Factors V Leiden and II 20210A vary in prevalence among patients with pulmonary embolism and deep vein thrombosis, suggesting that the risk of pulmonary embolization may vary among patients who have different causes of venous thromboses.     

Factor V Leiden and prothrombin G20210A mutations and the risk of atherothrombotic events in systemic lupus erythematosus.

Because genetic predisposition to atherothrombosis in systemic lupus erythematosus (SLE) remains to be determined, the most common genetic prothrombotic factors, prothrombin G20210A and factor V Leiden mutations, were studied. Seventy-four SLE patients with vascular ischemia (SLE cases) were studied and stratified into myocardial infarction and/or cerebrovascular accident subgroup (MI/CVA), and coronary heart disease subgroup without overt arterial thrombotic events (CHD). Seventy-one SLE patients without atherothrombosis were investigated as SLE controls. Factor V Leiden was detected in six cases (five in MI/CVA, one in CHD group) and three controls (OR 2.00, 95%CI 0.48-8.32). Two cases (both CHD patients) had prothrombin G20210A mutation vs. three controls (OR 0.63, 95%CI 0.1-3.88). Anticardiolipin antibodies (aCL) were increased in cases vs. controls (39/74 vs. 27/71); however, this was not statistically significant (OR 1.82, 95%CI 0.94-3.52). Neither univariate nor multivariate analysis indicated that investigated mutations are risk factors for atherothrombosis in SLE cases, MI/CVA, or CHD subgroups. Overall, disease activity was the strongest risk factor for atherothrombosis (p=0.0014) in SLE cases. Combination of disease activity+gender was the best predictor of atherothrombotic process (p=0.00045) in this cohort. In MI/CVA subgroup, disease activity was the only predictor (p=0.0058). In CHD patients, the best predictive value was conferred by combination of hypertension+gender+disease activity (p=0.00077). No other investigated risk factor (including aCL) conferred an increased risk individually or potentiated the other risk factors. The results deny the role of investigated mutations in atherothrombosis in SLE, but they underscore the importance of disease activity (i.e., ongoing inflammation) in pathogenesis of atherosclerosis and arterial thrombosis.     

Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction

Background Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification.Methods and Results To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with ≥1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, β-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism. The frequencies of Factor V Leiden and the β-fibrinogen 448 A allele were higher in patients with no flow-limiting stenosis than in patients with ≥1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P = .015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P = .018, respectively), and there was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs 2.1%, OR 3.4, 95% CI 0.95-11.8, P = .069). However, in patients with no flow-limiting stenosis after MI the frequencies of the other gene mutations/polymorphisms were not increased. Also, there were no significant interactions between any of these 14 mutation/polymorphisms, major cardiovascular risk factors, and the absence of any flow-limiting stenosis, except for Factor V Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P = .004).Conclusions Patients with no flow-limiting stenosis after MI had increased frequencies of 2 inherited thrombophilias (Factor V Leiden and β-fibrinogen 448 A allele), and there was a trend toward an increased frequency of prothrombin variant G20210A compared with patients with ≥1 stenosis. These data suggest that polymorphisms/mutations in some gene products influencing coagulation may influence the pathogenesis of MI. (Am Heart J 2003;145:118-24.)     

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.     

Factor V Leiden and inflammatory bowel disease: a systematic review and meta-analysis

Background

Recent studies proved that inflammatory bowel disease (IBD) patients had a higher risk of thromboembolism and a Factor V Leiden mutation that prevents the efficient inactivation of factor V, which leads to thromboembolism and thus contributes to a high potential risk of IBD. However, the relationship between Factor V Leiden mutation and IBD remains controversial.

Methods

We conducted a systematic review with meta-analysis of studies assessing the association of Factor V Leiden mutation with the risk of IBD in humans. We extracted the number of IBD and control subjects with or without Factor V Leiden mutation from each study and conducted this analysis using a fixed-effects model.

Results

Nineteen studies met the inclusion criteria and were included in the meta-analysis. No significant heterogeneity was found in results across the 19 studies (I ²?=?18.8%, P?=?0.23), which showed a slight but not significant increase in the risk of IBD with Factor V Leiden mutation in the general population (summary odds ratio [OR] 1.13, 95% confidence interval [CI] 0.87?C1.46). Taking into account ethnic differences, further study exhibited a slight but not significant increase in risk of IBD with Factor V Leiden mutation in Europeans (summary OR 1.20, 95% CI 0.88?C1.64). However, Factor V Leiden mutation was significantly associated with a higher risk of thromboembolism in IBD patients (summary OR 5.30, 95% CI 2.25?C12.48). No publication bias was found in this study.

Conclusions

This meta-analysis indicated that although Factor V Leiden mutation was not significantly associated with the risk of IBD, it was significantly associated with a higher risk of thromboembolism in IBD patients.     

Factor V leiden is a risk factor for myocardial infarction in young Turkish men

OBJECTIVE: Factor V Leiden is the most common known hereditary abnormality of the clotting system which leads to a reduced anticoagulant effect of activated protein C (APC resistance). FactorV Leiden has been shown to be the most frequent inherited thrombophilic disorder in patients with idiopathic venous thromboembolism. The relationship between this genetic abnormality and myocardial infarction is still unresolved. The aim of this study was to investigate whether factor V Leiden is a risk factor for myocardial infarction in young Turkish men or not. METHODS AND RESULTS: We compared 42 patients who had a diagnosis of acute MI and were younger than 40 years (35.6+/-4.8 years) with 66 healthy, age and sex-matched control subjects. Blood samples from the patients and the controls were analysed for the factor V Leiden mutation by DNA analysis, using polimerase chain reaction. Factor V Leiden mutation was found in 10 of 42 (23.8%) patients with myocardial infarction and 6 of 66 (9%) control subjects (p < 0.001).The odds ratio for MI was 3.1. (CI 95% 1.0-8.9) CONCLUSION: The results of this study suggest that the presence of factorV Leiden increases the risk of Ml in young Turkish men. ( Acta Cardiol 2004; 59(6): 594-597)     

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.     

Incidence of Factor V Leiden in Patients with Acute Myocardial Infarction

The genetic defect of coagulation factor V known as factor V Leiden produces a resistance to degradation by activated protein C (APC) and increases the risk of venous thromboembolism. The data on arterial thrombosis associated with APC resistance are still not clearly defined. We conducted a study in patients presenting with acute myocardial infarction (MI) to assess whether factor V Leiden increases the risk of arterial thrombosis. We studied 109 patients who had a diagnosis of acute MI (69 males and 40 females, aged 25–91 years), and 112 controls. The study population was identified by characteristic ECG changes and elevation of serum CK-MB, whereas the control subjects were anonymous healthy blood donors with no known history of coronary artery disease. Blood samples from the patients and controls were analyzed for the factor V Leiden mutation by DNA analysis, using the polymerase chain reaction. Heterozygous factor V Leiden mutation was found in 9 of 109 (8%) MI patients and 5 of 112 (4%) control subjects (P = .42). In conclusion, this study shows no evidence of an association between factor V Leiden and acute MI.     

Factor V Leiden,prothrombin gene mutation,and thrombosis risk in patients with antiphospholipid antibodies

OBJECTIVE: To determine if the prevalence of 2 prothrombotic genetic factors, factor V Leiden and prothrombin gene mutation, is increased in patients with antiphospholipid (aPL) antibodies with a history of venous/arterial thrombosis compared to patients with aPL antibodies with no history of thrombosis. METHODS: One hundred fifty-seven patients with aPL antibodies were studied. The occurrence of venous and arterial thrombotic events since the time of antibody detection was determined retrospectively, using appropriate clinical and diagnostic criteria. Clinical risk factors for thrombosis were documented and included hypertension, hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral contraceptive, pregnancy, trauma, hospitalization, varicose veins, and malignancy. Genomic DNA was extracted from blood cells for determination of factor V Leiden mutation G1691 --> A and prothrombin mutation G20210 --> A by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Of 157 patients, 69 had a history of thrombosis (venous 37, arterial 32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus anticoagulant (LAC). The prevalence of factor V Leiden in patients with thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI 0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial thrombosis had factor V mutation compared to 3.5% of patients without thrombosis (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5 patients, none of whom had thrombosis. Stepwise logistic regression analysis indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03) were the strongest risk factors for developing thrombosis and that no additional risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation. CONCLUSION: Although the prevalence of factor V Leiden is modestly increased in patients with autoimmune aPL antibodies and thrombosis, these results suggest that its detection does not significantly increase the risk of a thrombotic event, once other clinical risk factors have been considered. Prothrombin gene mutation is not associated with thrombosis in patients with aPL antibodies.     

The prevalence of factor V Leiden as a risk factor for venous thromboembolism in the population of North-Western Greece.

BACKGROUND: Many predisposing factors have been associated with the development of venous thromboembolism. Recently, Factor V Leiden has been described as a common genetic risk factor. The geographic distribution of this genetic abnormality in the general population greatly varies. The prevalence of the Factor V Leiden mutation in Europe is high, particularly in Greece, where according to some authors it is especially high. The purpose of this study was to estimate the prevalence of the Factor V Leiden mutation in patients presenting with at least one episode of venous thromboembolism and to compare it with that of the general population. METHODS: Blood samples were drawn from 388 subjects. 240 healthy blood donors (controls) and 148 unselected patients with a history of one or more episodes of venous thrombosis. DNA analysis was performed using the polymerase chain reaction to amplify the factor V gene exon 10, and to detect the Factor V Leiden point mutation. RESULTS: DNA analysis revealed Factor V Leiden mutations in eight (3.3%) control subjects (seven heterozygous and one homozygous) and in twenty-four (16.2%) patients, (twenty-two heterozygous and two homozygous). The difference between the two groups is statistically significant (p<0.0001; chi2 test). CONCLUSIONS: The prevalence of the Factor V Leiden mutation in the general population of North-Western Greece is 3.3%, which is within the same range as that reported for other European countries. The Factor V Leiden mutation is one of the most important predisposing genetic factors in the development of venous thrombosis and was present in 16.2% of our patients.     

Factor V Leiden and its relation to left ventricular thrombus in acute myocardial infarction

OBJECTIVE: The genetic defect of coagulation factor V, known as factor V Leiden, produces a resistance to degradation by activated protein C (APC) and increases the risk of venous thrombosis. However, the role of factor V Leiden in the formation of left ventricular (LV) thrombus has not been studied. We investigated whether factor V Leiden is a risk factor for LV thrombus in patients with acute myocardial infarction (AMI). METHODS and RESULTS: We have analyzed clinical, echocardiographic and biochemical data in 135 consecutive patients (aged 58 +/- 13 years; 31 women) with first anterior AMI. Two-dimensional echocardiographic examination was performed on days 1, 3, 7, 15 and 30; LV thrombus was detected in 33 (24.4%) of 135 patients with AMI. The study also included 95 control subjects. Healthy age and sex-matched subjects without a personal or family history of ischaemic heart disease, stroke or thromboembolic disease served as a control group. Blood samples from the patients and controls were analyzed for the factor V Leiden mutation by DNA analysis, using the polymerase chain reaction. In addition, concentrations of fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer were measured in 135 patients. There was no significant difference in the prevalence of factor V Leiden between patients and control subjects. The prevalence of the factor V mutation was 9% (3/33) in patients with thrombus, and 7.7% (8/103) in patients without thrombus. The prevalence of factor V Leiden was 7.3% (7/95) in control subjects. No significant differences in plasma fibrinogen (480 +/- 195 vs. 444 +/- 179 mg/dl, p = 0.6), D-dimer (471 +/- 256 vs. 497 +/- 293 ng/dl, p = 0.7), vWF (112 +/- 18 vs. 103 +/- 15%, p=0.5), PAI-1 (26.7+/- 9.8 vs. 28.1 +/- 10.2 ng/dl, p = 0.6), and t-PA (19.8 +/- 8.7 vs. 17.2 +/- 9.1 ng/dl, p = 0.7), levels are found in patients with LV thrombus when compared with those without LV thrombus. Multivariate analyses showed that peak creatine kinase level (p = 0.002) and LV wall motion score index (p = 0.003) were independent predictors of LV thrombus formation. CONCLUSION: Factor V Leiden mutation is not a risk factor for LV thrombus formation in patients with AMI.     

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.     

Prevalence of factor V Leiden (APCR) and other inherited thrombophilias in young patients with myocardial infarction and normal coronary arteries

Objective—To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis.
Methods—The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects.
Results—Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57).
Conclusions—The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future.

Keywords: myocardial infarction; factor V Leiden; coagulation factors; inherited thrombophilia     

Lack of association between factor V Leiden and thromboembolism in patients with prosthetic heart valves.

Thromboembolism represents the most serious complication in patients with prosthetic heart valves, and causes significant mortality and morbidity. Many risk factors for the condition have been identified. However, many patients who have a therapeutic level of anticoagulation and no obvious risk factors develop thromboembolism. Factor V Leiden, found in 3-7% of the normal population, is the most common inherited factor associated with thrombosis. Whether or not this factor is associated with thromboembolism in this setting has not been explored. This study compares the prevalence of factor V Leiden in patients with prosthetic heart valves, with and without thromboembolic complications. A total of 148 patients were studied. Thirty had documented thromboembolic complications and none exhibited the factor V mutation. Of the 118 patients without thromboembolic complications, seven (5.9%) were heterozygous for factor V Leiden (P = 0.345, by Fisher's two-tailed exact test; odds ratio 0, 95% confidence interval 0.0-4.34). We conclude that until future data shows otherwise, routine testing for factor V Leiden in patients with prosthetic heart valves is not warranted, except as part of ongoing research.     

Prevalence of resistance against activated protein C resulting from factor V Leiden is significantly increased in myocardial infarction: investigation of 507 patients with myocardial infarction

Background

A point mutation in the gene encoding coagulation factor V is a cause of resistance against activated protein C. The presence of factor V Leiden is linked to 50% of congenital defects causing venous thrombosis. Its relationship to arterial thrombosis, particularly to myocardial infarction, has not been defined. Therefore, we performed a study on the role of factor V Leiden in patients with myocardial infarction. The study was carried out in Bavarians of German origin, a relatively homogeneous population.

Methods and results

The study group consisted of 507 patients with documented myocardial infarction (77.5% (393/507) men, 22.5% (114/507) women), with a mean age of 56.1 (range 18--86) years. Strict criteria for patient selection and highly sensitive and specific functional tests for factor V Leiden were used. In addition, all patients with pathological test results were genotyped. The prevalence of factor V Leiden in patients with myocardial infarction was 8.7% (44/507), a significant increase in the prevalence of this mutation compared with the control group (3.7%, P = .0025). The odds ratio was 2.46 (95% CI 1.35-4.50).

Conclusions

A significantly increased prevalence of factor V Leiden in patients with documented myocardial infarction was seen. Patients with this mutation appear to have a predisposition for myocardial infarction.     

Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses

Factor V Leiden (FVL) is associated with venous thrombosis; however, an association between FVL and arterial thrombosis remains controversial. We investigated FVL as a risk factor for myocardial infarction (MI), ischemic stroke (IS), or non-MI ischemic heart disease (non-MI-IHD). The design was 3 case-control studies and 3 prospective studies with 21 years' follow-up. The setting was the general population in Copenhagen, Denmark. The participants for The Copenhagen City Heart Study were 20- to 95-year-old participants without cardiovascular disease (control population, n = 7907) or participants diagnosed with MI (n = 469), IS (n = 231), or non-MI-IHD (n = 365). In addition, 3 independent patient populations from Copenhagen University Hospital with MI (n = 493), IS (n = 231), or non-MI-IHD (n = 448) were included. We measured FVL genotype; major cardiovascular risk factors; and MI, IS, and non-MI-IHD incidence and prevalence. Prevalences of FVL heterozygotes and homozygotes in control subjects from the general population were 7.7% and 0.2%. Odds ratios and relative risks of MI in FVL carriers (heterozygotes + homozygotes) versus noncarriers were 1.24 (95% confidence interval [CI], 0.91-1.69) and 0.83 (0.58-1.20) in case-control and prospective studies, respectively. Corresponding risks for IS were 0.92 (95% CI, 0.56-1.53) and 0.68 (0.45-1.04), and for non-MI-IHD 1.01 (95% CI, 0.71-1.44) and 0.97 (0.66-1.42). Findings from The Copenhagen City Heart Study suggest that FVL is not associated with MI, IS, or non-MI-IHD.     

Factor V Leiden mutation in cerebrovascular disease.

Several studies indicate a high prevalence of factor V Leiden mutation as the most frequent coagulation defect found in patients with venous thrombosis. The relationship between this mutation and cerebrovascular disease has not been established in adults. In this investigation, we studied 29 patients with ischemic stroke and 20 with intracerebral hemorrhage, all of whom were compared with 20 controls. A region of the factor V gene containing the Leiden mutation site was amplified with polymerase chain reaction and the presence of mutation was determined with restriction enzyme digestion. We found no evidence of an association between factor V Leiden mutation and ischemic stroke or intracerebral hemorrhage. There was no evidence of association in subgroup the analysis by age, smoking status, myocardial infarction, hypertension, diabetes mellitus, or coronary disease. Factor V Leiden mutation doesn't seem to be associated with a risk of cerebrovascular disease.     

Factor V Leiden related Budd-Chiari syndrome

BACKGROUND: The role of factor V Leiden as a cause of Budd-Chiari syndrome has only recently been described. AIMS: To assess the specific features of factor V Leiden related Budd-Chiari syndrome. PATIENTS: Sixty three consecutive patients with hepatic vein or terminal inferior vena cava thrombosis. METHODS: Standardised chart review. RESULTS: Factor V Leiden was found in 20 patients (31% (95% CI 20-43)). In the subgroup of patients with, compared with the subgroup without, factor V Leiden, a combination of prothrombotic states was more common (70% (95% CI 50-90) v 14% (95% CI 3-24)); inferior vena cava thrombosis was more frequent (40% (95% CI 19-61) v 7% (95% CI 0-14)); and distribution of initial alanine aminotransferase values was bimodal (almost normal or extremely increased) versus unimodal (p=0.003). Factor V Leiden accounted for four of five cases of massive ischaemic necrosis (transaminases >50-fold the upper limit of normal values) (p=0.014), and also for all three cases developing during pregnancy. Patients with and without factor V Leiden did not differ with regard to mortality, portosytemic shunting, or listing for liver transplantation. Hepatocellular carcinoma developed in two patients; both had factor V Leiden and indolent obstruction of the inferior vena cava. CONCLUSIONS: In patients with Budd-Chiari syndrome, factor V Leiden (a) is common; (b) precipitates thrombosis mostly when combined with another risk factor; (c) is associated with one of two contrasting clinical pictures: indolent thrombosis-particularly of the inferior vena cava-or massive ischaemic necrosis; and (d) is a major cofactor of Budd-Chiari syndrome developing during pregnancy.     

Risk of thrombosis in patients with antiphospholipid antibodies and factor V Leiden mutation

OBJECTIVE: Antiphospholipid antibodies (aPL) are thrombophilic risk markers in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). The risk factors for recurrent venous or arterial thrombosis and indications for longterm anticoagulation therapy are debated. We hypothesized that carrying a second thrombophilic defect, factor V Leiden mutation, would increase the risk for thrombosis in patients with aPL. METHODS: Seventy-five patients with primary APS and 83 with SLE and aPL with or without thrombosis followed at 2 university hospitals were studied. Factor V mutation rate was analyzed in patients and in 200 healthy blood donors by polymerase chain reaction analysis. RESULTS: The prevalence of factor V Leiden mutation in patients with SLE and aPL or primary APS was similar to controls. Patients with deep vein thrombosis or arterial thrombosis did not have a significantly increased rate of factor V mutation compared to controls or to patients with aPL without thrombosis. CONCLUSION: Factor V Leiden mutation is not significantly associated with vein thrombosis in patients with aPL. However, due to the sample size we cannot rule out synergy between both factor V Leiden and aPL. A trend toward increased risk for thrombosis was detected in patients with the mutation and this should be analyzed in a larger study.