Thromb Haemostasis
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Randomized Controlled Trial Comparative Study Clinical Trial
Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation.
Compared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation. In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. ⋯ In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (-14.2; 95% CI -22.4 to -6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (-9.5; 95% CI -18.3 to -0.6). It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrel-containing oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.
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Cytokines increase endothelial tissue factor (TF) and tissue plasminogen activator inhibitor type-1 (PAI-1) expression in vitro. Tissue factor interacts with factor VII to facilitate thrombosis and PAI-1 inhibits fibrinolysis by endogenous plasminogen activators. Because cytokine release is increased in children with sepsis-induced multiple organ failure (MOF), we hypothesized a cytokine associated increase in circulating TF and PAI-1 antigen release, and systemic activity in these patients. ⋯ A shift to an anti-fibrinolytic endothelium phenotype characterizes children who develop sepsis-induced MOF and mortality. Children with coagulopathy have a shift to a pro-coagulant phenotype. These findings support potential therapeutic roles for PAI-1 and TF pathway inhibitors in reversal of this devastating pathophysiologic process.
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The present study was initiated to evaluate the safety and efficacy of Haemate-P (Humate-P in North America) (anti-hemophilic FVIII/VWF complex [human] dried, pasteurized) dosed in ristocetin cofactor units (VWF:RCo) in the treatment of von Willebrand disease (VWD) patients in Canada. This retrospective data collection reviewed the medical records of VWD patients treated under the Canadian Emergency Drug Release Program from November 22, 1991, to April 30, 1996. Data collection was accomplished by on-site retrieval from source data for 97 patients. ⋯ A pediatric sub-population analysis of the patient population reported "excellent/good" efficacy in 100% (17/17) of treatment events in infants, 95% (155/164) in children, and 94% (76/81) in adolescent patients. Related adverse events (AEs) were observed in only 4 (4%) patients and were not deemed to be serious. The findings in this study confirm the safety and efficacy of Haemate-P/Humate-P using VWF:RCo dosing in pediatric and adult patients with various types of VWD.