The efficacy of tissue factor −603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients

Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings

Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study

OBJECTIVE: Dabigatran was recently approved for anticoagulation in patients with atrial fibrillation (AF); data regarding real-world use, comparative effectiveness and safety are sparse. DESIGN: Pharmacoepidemiological cohort study. METHODS/SETTINGS: From nationwide registers, we identified patients with an in-hospital or outpatient-clinic AF diagnosis who claimed a prescription of dabigatran 110 or 150 mg, or vitamin K antagonist (VKA), between 22 August and 31 December 2011. HRs of thromboembolic events (ischaemic stroke, transitory ischaemic attack and peripheral artery embolism) and bleedings were estimated using Cox regression analyses in all patients and stratified by previous VKA use. RESULTS: Overall, 1612 (3.1%) and 1114 (2.1%) patients claimed a prescription of dabigatran 110 and 150 mg, and 49640 (94.8%) of VKA. Patients treated with dabigatran 150 mg were younger with less comorbidity than those treated with dabigatran 110 mg and VKA, as were VKA naïve patients compared with previous VKA users. Recommendations set by the European Medicine Agency (EMA) for dabigatran were met in 90.3% and 55.5% of patients treated with 110 and 150 mg. Patients treated with 150 mg dabigatran, who did not fulfil the recommendations by EMA, were >80 years, patients with liver or kidney disease, patients with previous bleeding. Compared with VKA, the thromboembolic risk associated with dabigatran 110 and 150 mg was HR 3.52 (1.40 to 8.84) and 5.79 (1.81 to 18.56) in previous VKA users, and HR 0.95(0.47 to 1.91) and 1.14(0.60 to 2.16) in VKA naïve patients. Bleeding risk was increased in previous VKA users receiving dabigatran 110 mg, but not in patients with 150 mg dabigatran, nor in the VKA naïve users. CONCLUSIONS: Deviations from the recommended use of dabigatran were frequent among patients treated with 150 mg. With cautious interpretation, dabigatran use in VKA naïve patients seems safe. Increased risk of thromboembolism and bleeding with dabigatran among previous VKA users was unexpected and may reflect patient selection and ‘drug switching’ practices

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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A Link Between Cytotoxicity in Cell Culture and Gastrointestinal Side Effects of Oral Anticoagulants: Bench-To-Bedside

OBJECTIVE: Warfarin and nonvitamin-K oral anticoagulants including dabigatran, rivaroxaban, and apixaban are commonly used in the prophylaxis and treatment of systemic embolism and deep vein thrombosis. In this study, we aimed to compare the cytotoxic effects of warfarin and new oral anticoagulants and to show a possible correlation between cell cytotoxicity and gastrointestinal side effects in the real-life setting. METHODS: L929 cells were incubated with test materials. At 24 and 48 hours, morphological changes and cell viability were evaluated. RESULTS: At 24 and 48 hours, dabigatran resulted in altered cell morphology in all dilutions, while rivaroxaban, apixaban, and warfarin showed similar morphology with the control group, except for dilution I. Dabigatran and warfarin at 24 hours and at 48 hours had a statistically significantly lower cell viability in all dilutions, compared to the control group. CONCLUSION: Gastrointestinal side effect profiles of these four agents in a real-life setting is consistent with the results obtained from the present study. There is no sole factor with the potential of explaining the entire gastrointestinal side effect profiles of anticoagulant agents. However, direct cytotoxic effects of anticoagulants should be considered primarily for gastrointestinal side effects in accordance with the results of present head-to-head cytotoxicity study (Tab. 5, Fig. 3, Ref. 28). Text in PDF www.elis.sk.WoSScopu

THE EFFICACY OF TISSUE FACTOR −603A/G AND +5466A>G POLIMORPHISMS AT THE DEVELOPMENT OF VENOUS THROMBOEMBOLISM IN CANCER PATIENTS

Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings

Deletion analysis and clinical correlations in patients with Xp21 linked muscular dystrophy

PubMed ID: 15641267We carried out molecular deletion analysis on 142 patients with Duchenne/Becker muscular dystrophy which covered 25 exons of the dystrophin gene. We also evaluated the results by comparing with the clinical findings and examples in the literature. A deletion ratio of 63.7% was achieved. Exon 46 was the most frequently affected region. Interestingly we also observed four cases with muscle promoter (Mp) region deletions which have been rarely reported in the literature

Deletion analysis and clinical correlations in patients with Xp21 linked muscular dystrophy

We carried out molecular deletion analysis on 142 patients with Duchenne/Becker muscular dystrophy which covered 25 exons of the dystrophin gene. We also evaluated the results by comparing with the clinical findings and examples in the literature. A deletion ratio of 63.7% was achieved. Exon 46 was the most frequently affected region. Interestingly we also observed four cases with muscle promoter (Mp) region deletions which have been rarely reported in the literature