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.     

Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients

Cancer patients have an increased risk of venous thrombosis (VT). The association of factor V Leiden (FVL) and the prothrombin 20210A variant with VT in cancer patients is not established. We genotyped 101 cancer patients with VT and 101 cancer patients without VT for these polymorphisms. Five cases and three controls were heterozygous for FVL, yielding an odds ratio of 1.7 (95% confidence interval (CI) 0.3-10.7). Five cases and no controls were heterozygous for prothrombin 20210A, for an odds ratio of 6.7 (95% CI 0.9-infinity). Prothrombin 20210A may be associated with VT risk among cancer patients.     

Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients

Several inherited polymorphisms are associated with risk of venous thrombosis, including mutation at codon 506 of the factor V gene, mutation at position 20210 of the prothrombin gene, and mutations in the protein C gene. In this study, genotyping for factor V, prothrombin, and protein C mutations was performed in 50 patients and 25 control subjects by polymerase chain reaction-based analysis. The prevalence of factor V and prothrombin mutations was not significantly different from that in the general population. Nine of the patients had heterozygous protein C mutation. There was a high prevalence of the mutated protein C allele in the pulmonary emboli group (42.8%). Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups. These results indicate that patients with protein C deficiency have a greater risk of thrombosis than patients with factor V or prothrombin G20210A mutation.     

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.     

Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in Mediterranean area

Background. Thromboembolism has been reported to be associated with inflammatory bowel disease.Aim. To evaluate the association of factor V Leiden and prothrombin gene mutation with inflammatory bowel disease in a population of patients with thromboembolic events and inflammatory bowel disease and in a control population of patients with inflammatory bowel disease without thromboembolic events.Patients and methods. A series of 18 patients with inflammatory bowel disease and a history of arterial or venous thrombosis and 45 patients with inflammatory bowel disease without thromboembolic events were evaluated for the presence of factor V Leiden and prothrombin gene mutation. Frequency of gene mutation was compared with its occurrence in 100 healthy controls.Results. One patient with inflammatory bowel disease without thromboembolic events was heterozygous for factor V Leiden mutation. whereas no patient with a thromboembolic event had factor V Leiden mutation. No patients (either cases or controls) had prothrombin gene mutation. In the healthy population the frequency of factor V Leiden and prothrombin mutation was 5% and 2%, respectively.Conclusions. Data emerging from the present study do not support any role of factor V Leiden and prothrombin gene mutation as the cause of thromboembolism in inflammatory bowel disease.     

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.     

Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study

In a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). We compared 43 BCS patients and 92 PVT patients with 474 population-based controls. The relative risk of BCS was 11.3 (95% CI 4.8-26.5) for individuals with factor V Leiden mutation, 2.1(95% CI 0.4-9.6) for those with prothrombin gene mutation, and 6.8 (95% CI 1.9-24.4) for those with protein C deficiency. The relative risk of PVT was 2.7 (95% CI 1.1-6.9) for individuals with factor V Leiden mutation, 1.4 (95% CI 0.4-5.2) for those with prothrombin gene mutation, and 4.6 (95% CI 1.5-14.1) for those with protein C deficiency. The relative risk of BCS or PVT was not increased in the presence of inherited protein S or antithrombin deficiency. Concurrence of either acquired or inherited thrombotic risk factors was observed in 26% of the BCS patients and 37% of the PVT patients. We conclude that factor V Leiden mutation and hereditary protein C deficiency appear to be important risk factors for BCS and PVT. Although the prevalence of the prothrombin gene mutation was increased, it was not found to be a significant risk factor for BCS and PVT. The coexistence of thrombogenic risk factors in many patients indicates that BCS and PVT can be the result of a combined effect of different pathogenetic mechanisms.     

Factor V Leiden mutation in venous thrombosis in southeast Turkey

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.     

Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in a Mediterranean area.

BACKGROUND: Thromboembolism has been reported to be associated with inflammatory bowel disease. AIM: To evaluate the association of factor V Leiden and prothrombin gene mutation with inflammatory bowel disease in a population of patients with thromboembolic events and inflammatory bowel disease and in a control population of patients with inflammatory bowel disease without thromboembolic events. PATIENTS AND METHODS: A series of 18 patients with inflammatory bowel disease and a history of arterial or venous thrombosis and 45 patients with inflammatory bowel disease without thromboembolic events were evaluated for the presence of factor V Leiden and prothrombin gene mutation. Frequency of gene mutation was compared with its occurrence in 100 healthy controls. RESULTS: One patient with inflammatory bowel disease without thromboembolic events was heterozygous for factor V Leiden mutation. whereas no patient with a thromboembolic event had factor V Leiden mutation. No patients (either cases or controls) had prothrombin gene mutation. In the healthy population the frequency of factor V Leiden and prothrombin mutation was 5% and 2%, respectively. CONCLUSIONS: Data emerging from the present study do not support any role of factor V Leiden and prothrombin gene mutation as the cause of thromboembolism in inflammatory bowel disease.     

Lupus anticoagulant,Factor V Leiden,and methylenetetrahydrofolate reductase gene mutation in a lupus patient with cerebral venous thrombosis

We describe the case of a young Lebanese woman with systemic lupus erythematosus (SLE) and a positive lupus anticoagulant (LAC) who developed right internal jugular vein and sigmoid sinus thrombosis. Coagulation studies showed that in addition to the LAC the patient was heterozygous for the factor V (FV) Leiden mutation, and C677T mutation of the methylenetetrahydrofolate reductase gene. The high prevalence of FV Leiden in the eastern Mediterranean region suggests that we should probably screen our SLE patients in this area, especially those with anticardiolipin antibodies and/or LAC who have no history of thrombosis, for this and other thrombophilia markers. The detection of such abnormalities may have major practical consequences for the long-term management of these patients to prevent further thrombotic episodes.Abbreviations APS Antiphospholipid syndrome - CVT Cerebral venous thrombosis - LAC Lupus anticoagulant - DVT Deep vein thrombosis - SLE Systemic lupus erythematosus - SVC Superior vena cava     

Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale.

The role of paradoxical embolism through patent foramen ovale as a mechanism of cryptogenic stroke is controversial. If a venous source of emboli is relevant, prothrombotic states should be associated with patent foramen ovale and cryptogenic stroke. We assessed the occurrence of several prothrombotic states (factor V Leiden, prothrombin G20210A, deficiencies in protein S, protein C and antithrombin, lupus anticoagulant, anticardiolipin antibodies, elevated factor VIII, resistance to activated protein C) and classical risk factors for venous thrombosis in 57 adult patients with cryptogenic stroke and patent foramen ovale and in 104 matched controls. Prothrombotic states [odds ratio (OR) 2.8; 95% confidence interval (CI), 1.2-6.5; P = 0.021], migraine with aura (OR 4.4; 95% CI 1.8-10.8; P = 0.001) and classical risk factors for venous thrombosis (OR 2.5; 95% CI 1.1-5.7; P = 0.037) were independent risk factors for cryptogenic stroke. In particular factor V Leiden or prothrombin G20210A associated with cryptogenic stroke (P = 0.022) whereas other coagulation abnormalities did not (P = 0.140). Among the patients with prothrombotic states, Valsalva manoeuvre was common at onset of stroke. Our results support the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale.     

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.

     

Factor V Leiden and prothrombin gene G20210A mutations are uncommon in portal vein thrombosis in India.

BACKGROUND: Extra-hepatic portal vein obstruction due to portal vein thrombosis (PVT) is an important cause of portal hypertension in several regions including India. The cause of thrombosis in these patients remains unclear. We studied the frequency of mutations in genes for coagulation factors V and II (prothrombin) in 61 Indian patients with PVT and 49 healthy control subjects. METHODS: The presence of factor V Leiden mutation and of G20210A prothrombin gene mutation was determined using polymerase chain reaction followed by restriction fragment length polymorphism. Chi-squared test was used to compare patients and controls. RESULTS: Of the 61 patients (median age 11 years; 47 male) studied, 49 were children. One of 61 (1.6%) patients with PVT was heterozygous for factor V Leiden mutation and none had the G20210 prothrombin gene mutation. The frequencies of these mutations were not different from those in control subjects (2/49 and 0/46, respectively). CONCLUSION: Factor V Leiden and G20210 prothrombin gene mutations are infrequent in Indian patients with PVT. Thus, these mutations are unlikely to be responsible for PVT in the Indian population.     

Homozygous factor V Leiden and double heterozygosity for factor V Leiden and prothrombin mutation

The most common forms of familial thrombophilia are factor V Leiden (FVL) and prothrombin mutation (PTM). Homozygous FVL and PTM have long been feared conditions thought to cause high rates of morbidity and mortality. To analyse clinical features in patients with homozygous FVL and PTM, as well as patients with double heterozygosity for FVL and PTM. All patients with homozygous FVL, PTM or double heterozygosity in the MATS database of 1465 consecutive unselected patients were analysed regarding age at inclusion venous thromboembolism (VTE), age at first thrombosis, recurrence, clinical course and acquired risk factors. We found 36 patients homozygous for FVL. Patients homozygous for FVL were younger than controls at group level (56 ± 18 vs. 63 ± 17, p < 0.02). Homozygous women were younger than female controls (50 ± 19 vs. 63 ± 18, p < 0.002). No difference was observed when comparing male subjects. Women were younger than men at inclusion thrombosis (50 ± 19 vs. 65 ± 14, p < 0.02) and at first thrombosis (47 ± 19 vs. 64 ± 14, p < 0.01). Deep venous thrombosis (DVT) was seen in 33 patients (92 %), 6 (17 %) had pulmonary embolism (PE) and 3 (8 %) had combined DVT and PE. PE was less frequent in homozygous FVL women compared to female controls (p < 0.03). VTE recurred in 3 subjects during the duration of the study. Odds ratio for VTE in homozygous FVL patients compared to controls was 13.9 (95 % CI 9.9–19.7). We found no subjects with homozygous PTM. Double heterozygosity for FVL and PTM was seen in 12 subjects. There was no difference in age at inclusion VTE between double heterozygotes and controls (59 ± 16 vs. 63 ± 17, ns.). DVT was seen in 92 % at inclusion, 8 % had PE. Mean age at first VTE was 52 ± 17 (27–82). Consecutive homozygous FVL patients had a higher age at first thrombosis than previously described. Homozygous females are affected at an earlier age than homozygous men and female controls. It seems that thrombi in homozygous FVL have a different pattern compared to controls i.e. more prone for thrombosis in the lower extremity. The odds ratio for thrombosis among homozygous FVL seems to be lower than previously described.     

Factor V Leiden mutation in Turkish patients with homozygous cystathionine beta-synthase deficiency

Venous and arterial thromboembolism can occur in patients with homocystinuria. Resistance to activated protein C, which is caused by a single point mutation in the gene for factor V, renders an individual at risk for thrombosis. It has been suggested that coexistence of hereditary homocystinuria and factor V Leiden mutation might jointly play a role in the development of thrombosis. We analysed six patients with homocystinuria due to cystathionine -synthase deficiency for factor V Leiden and prothrombin G20210A mutations. Only one patient was found to have the factor V Leiden mutation in homozygous form and this patient had suffered from severe thrombosis. One patient was found to be heterozygous with no documented thrombosis. None of the patients had prothrombin G20210A mutation. We stress the necessity for screening for known thrombophilic risk factors in patients with cystathonine -synthase deficiency. The coexistence of the factor V Leiden mutation can cause severe thrombotic events in patients with homocystinuria.