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Denas G Marzot F Offelli P Stendardo A Cucchini U Russo R Nante G Iliceto S Pengo V 《Journal of thrombosis and thrombolysis》2009,27(3):340-347
Background Timely reversal of excessive anticoagulation is important in preventing bleeding complications. The use of vitamin K in correcting
over-anticoagulation is widely accepted to be superior to discontinuation of therapy but its effectiveness and safety in large
scale cohort studies has not been assessed. Methods According to our protocol, 2 mg of oral vitamin K in addition to omitting the day’s dose of warfarin, were administered to
all patients presenting INR levels ≥5.0 and below 10.0; the INR values were checked 20 h after vitamin K administration. The
rate of decay of INR, bleeding and thromboembolic complications at presentation and the following 30 days, as well as resistance
to warfarin were assessed. Results Of the 1,611 events, 1,043 (878 patients) met the selection criteria. The median (interquartile range) INR was 6.64 (6.12–7.52)
at presentation (day zero) and fell to a median (interquartile range) INR of 2.72 (2.18–3.52, P < 0.0001) after the vitamin K administration (day one) and 90.6% of the INRs were below 4.5. In 98 (9.4%) instances the INR values did not fall below the safe limit of 4.5 and
in 173 (17%) instances the INR values were overcorrected to below 2.0. Median INR value on day zero in these two groups was higher (7.3 vs. 6.6, P < 0.0001) and lower (6.5 vs. 6.7, P = 0.049) than that of the remaining cases, respectively. Overcorrection occurred more frequently in women (P = 0.0002). Female gender was an independent factor associated with INR overcorrection (P = 0.001; OR = 1.7, 95% CI 1.3–2.3). The INRs on day one were inside, above and below the therapeutic range in 44%, 36% and 20% respectively. Warfarin resistance was observed in
six cases (0.6%). Major bleeding was reported in one case (1.1 per 100 patient-years), minor bleeding in 14 cases (16.1 per
100 patient-years) and thromboembolic events in six high risk patients (6.9 per 100 patient-years) during the one month period
following vitamin K administration. Conclusions This adopted protocol for the reversal of excessive anticoagulation in asymptomatic or minor symptom presenting patients
is easily applied, effective in lowering the INR and preventing complications. Its use in high risk thromboembolic patients
warrants caution. 相似文献
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Matsushita K Imamura T Tomikawa M Tancharoen S Tatsuyama S Maruyama I 《Journal of periodontal research》2006,41(2):148-156
OBJECTIVE: Arginine-specific cysteine proteases (Rgps) from Porphyromonas gingivalis are important virulent factors of periodontal diseases. However, there is no therapeutic drug that inhibits proinflammatory events induced by these enzymes. In this study, we investigated proinflammatory activities of Rgps and activated coagulation factor X (FXa) and examined the effect of DX-9065a, a new selective inhibitor of FXa, on proinflammatory events induced by these proteinases. METHODS: Human gingival fibroblasts were stimulated with Rgps and FXa in the presence or absence of DX-9065a, and then interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) release, their mRNA expression, and nuclear factor kappaB (NF-kappaB) activation were assessed using an enzyme-linked immunosorbent assay (ELISA), northern blotting, and a gel-mobility shift method, respectively. RESULTS: Rgps and FXa activated IL-6 and MMP-1 release in human gingival fibroblasts through their amidolytic activities and in mitogen-activated protein kinase (MAPK) and NF-kappaB dependent manners. DX-9065a inhibited FXa-induced IL-6 mRNA expression and NF-kappaB activation. DX-9065a inhibited amidolytic activities of FXa and Rgps in vitro and ex vivo. CONCLUSION: Rgps and FXa are potent inflammatory mediators and DX-9065a may be a useful therapeutic drug for periodontal disease. 相似文献
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INTRODUCTION: The aim of this study was to evaluate endothelial function in patients with primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS: Flow mediated (FMD) and glyceryl trinitrate (GTN) induced dilation of the right brachial artery were studied in 25 patients with PAPS and 25 controls matched by age, sex and conventional risk factors for atherosclerosis. Fibrinogen, D-dimer, adhesion molecules, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigens and activities were measured. RESULTS: Mean (SD) FMD was significantly lower in PAPS than in controls (8+/-5% vs. 15+/-6%, P<0.001); GTN-induced dilation did not differ between the groups. There was a correlation between the baseline diameter of the brachial artery and duration of the disease (-0.56, P<0.05) and between GTN induced dilation and duration of the disease (0.51, P<0.05). Concentrations of vascular cell adhesion molecule-1 (P<0.001), intracellular adhesion molecule-1 (P<0.001) and fibrinogen (P<0.05) were higher in patients than in controls but no differences were observed for D-dimer, t-PA and PAI-1 antigens and activities. There was correlation between concentration of vascular cell adhesion molecule-1 and FMD (-0.35, P<0.05) and between intracellular adhesion molecule-1 and FMD (-0.41, P<0.05). CONCLUSIONS: This study shows that endothelial function is impaired in patients with primary APS, possibly contributing to accelerated atherosclerosis and thromboembolic complications in these patients. 相似文献
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