Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators.

BACKGROUND: In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial. METHODS: Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up. RESULTS: The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent). CONCLUSIONS: In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued.

Management of thromboembolism in the outpatient setting.

Low-molecular-weight heparins (LMWHs) are suitable for self-administration at home, because they have a predictable anticoagulant effect following subcutaneous injection and do not require laboratory monitoring. Clinical trials evaluating the safety and efficacy of LMWHs in the outpatient setting for the prevention of deep vein thrombosis (DVT) after orthopedic surgery and for the treatment of established DVT are reviewed. Extended LMWH prophylaxis reduces the incidence of venographically detected DVT by approximately 50%. Medical practice relies heavily on clinical diagnosis of DVT, for which both sensitivity and specificity are poor. It is uncertain how the results of research trials on DVT prevention based on venography relate to ordinary practice. In the treatment of established DVT, there was no significant difference between outpatient management with LMWH and inpatient treatment with unfractionated heparin (UFH). However, outpatient management offered a considerable reduction in resource usage, with associated cost savings.

Kinetic evidence for two active sites in beta-D-fucosidase of Helicella ericetorum.

1. The kinetics of beta-D-fucosidase of the snail H. ericetorum have been studied. The enzyme shows beta-D-fucosidase, beta-D-glucosidase and beta-D-galactosidase activities, all associated in a single peak in both DEAE-cellulose chromatography and isoelectric focusing (p1 4.35), having the same optimal pH (5.0). 2. With the corresponding p-nitrophenyl glycosides as substrates, beta-D-fucosidase activity shows the lowest Km, the highest Vmax and the best Vmax/Km value; close activity values were obtained for beta-D-glucosidase, however, beta-D-galactosidase activity is much lower in this enzyme. 3. All the kinetic evidence suggests that this enzyme has two active sites: a fuco-gluco site and a galacto site. 4. beta-D-fucosidase and beta-D-glucosidase activities have similar Km, Vmax, Vmax/Km and Ki values; these values are very different from those of beta-D-galactosidase activity. beta-D-fucosides and beta-D-glucosides completely compete for a common active site in mixed-substrate experiments, while beta-D-galactosides only partially compete with both glycosides. 5. With delta-D-gluconolactone, the enzyme shows a hyperbolic mixed-type inhibition, mainly competitive for beta-D-fucosidase and beta-D-glucosidase activities (with the same inhibition sub-type), and predominantly non-competitive for beta-D-galactosidase activity (with different inhibition sub-type). With delta-D-gluconolactone more inhibition of beta-D-fucosidase and beta-D-glucosidase activities was found, and with gamma-D-galactonolactone, more inhibition of beta-D-galactosidase activity was detected. 6. The enzyme is activated by some carbohydrates, probably in relation with a transglycosylation mechanism.

[Glycosidases of various mollusks: general properties, kinetic studies and action on natural substrates]. / Glicosidasas de algunos moluscos: propiedades generales, estudios cinéticos y acción sobre substratos naturales.

The beta-N-acetylhexosaminidase, beta-glucuronidase, alpha-galactosidase, beta-galactosidase and alpha-L-fucosidase activities, in six different species of molluscs, have been studied. The optimum pH was acid in all cases, in agreement with the lysosomal origin of these enzymes. They generally show several pI in their isoelectrofocusing profiles. Kinetic studies with enzymes having several activities in one protein, i.e. beta-N-acetylhexosaminidase and beta-galactosidase, have been carried out with mixed substrates in order to determine the occurrence of several active sites. The action of these enzymes on glycosidic rests containing natural substrates has been studied by enzymatic hydrolysis.