Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. (49/402)

OBJECTIVE: To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease. DESIGN: Double blind placebo controlled randomised trial. SETTING: 85 general practices and nine hospital vascular clinics. PARTICIPANTS: 1568 men, mean age 68.2 years (range 35 to 92) at recruitment. INTERVENTIONS: Bezafibrate 400 mg daily (783 men) or placebo (785 men). MAIN OUTCOME MEASURES: Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points). RESULTS: Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years. CONCLUSIONS: Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.  (+info)

Distinct dose-dependent effects of plasmin and TPA on coagulation and hemorrhage. (50/402)

All thrombolytic agents in current clinical usage are plasminogen activators. Although effective, plasminogen activators uniformly increase the risk of bleeding complications, especially intracranial hemorrhage, and no laboratory test is applicable to avoid such bleeding. We report results of a randomized, blinded, dose-ranging comparison of tissue-type plasminogen activator (TPA) with a direct-acting thrombolytic agent, plasmin, in an animal model of fibrinolytic hemorrhage. This study focuses on the role of plasma coagulation factors in hemostatic competence. Plasmin at 4-fold, 6-fold, and 8-fold the thrombolytic dose (1 mg/kg) induced a dose-dependent effect on coagulation, depleting antiplasmin activity completely, then degrading fibrinogen and factor VIII. However, even with complete consumption of antiplasmin and decreases in fibrinogen and factor VIII to 20% of initial activity, excessive bleeding did not occur. Bleeding occurred only at 8-fold the thrombolytic dose, on complete depletion of fibrinogen and factor VIII, manifest as prolonged primary bleeding, but with minimal effect on stable hemostatic sites. Although TPA had minimal effect on coagulation, hemostasis was disrupted in a dose-dependent manner, even at 25% of the thrombolytic dose (1 mg/kg), manifest as rebleeding from hemostatically stable ear puncture sites. Plasmin degrades plasma fibrinogen and factor VIII in a dose-dependent manner, but it does not disrupt hemostasis until clotting factors are completely depleted, at an 8-fold higher dose than is needed for thrombolysis. Plasmin has a 6-fold margin of safety, in contrast with TPA, which causes hemorrhage at thrombolytic dosages.  (+info)

Characteristics and functional outcome of traumatic hyphema without routine administration of epsilon-aminocaproic acid. (51/402)

BACKGROUND: The prevalence of traumatic hyphema as well as the distribution of its severity varies among different patient populations. Treatment recommendations in the literature differ significantly among various published reports. This lack of a uniformly accepted treatment probably reflects the different characteristics of this pathology among the populations investigated and cells for a population-adjusted treatment recommendation. OBJECTIVES: To report the characteristics and functional outcome of patients with traumatic hyphema and to discuss possible recommendations regarding the use of epsilon-aminocaproic acid. METHODS: A prospective, non-randomized study was conducted in 154 consecutive patients with traumatic hyphema, including data collection of ophthalmic status at various time points, the presence or absence of secondary hemorrhage, and final visual acuity. RESULTS: Of the 154 eyes studied over 3 years, nearly 90% had hyphema of grade 1 or less, 5 (3.25%) experienced rebleeding, and 2 (1.3%)--neither of which rebled--needed surgical intervention. None of the four patients who experienced final visual acuity of 6/40 or less suffered rebleeding. CONCLUSION: The use of epsilon-aminocaproic acid in the studied population was unjustified and routine use of epsilon-aminocaproic acid in our patient population is probably not indicated. A treatment policy regarding epsilon-aminocaproic acid use should be adjusted to the population being treated.  (+info)

Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery. (52/402)

BACKGROUND: Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse. METHODS: Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo. RESULTS: The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01. CONCLUSIONS: Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.  (+info)

Plasma plasmin-alpha2-plasmin inhibitor complex levels are increased in systemic sclerosis patients with pulmonary hypertension. (53/402)

OBJECTIVE: To determine the frequency and clinical significance of plasma plasmin-alpha(2)-plasmin inhibitor complex (PIC) in patients with systemic sclerosis (SSc). METHODS: Plasma samples from 74 patients with SSc and 32 healthy volunteers were examined by a specific enzyme-linked immunosorbent assay. RESULTS: Elevated plasma PIC levels were present in 35 of the 74 patients (47.3%) with SSc. The patients with elevated plasma PIC levels had pulmonary hypertension (PH) at a significantly higher incidence than those with normal PIC levels (31.4 vs 7.7%, P<0.01). When PH was classified into isolated PH (IPH) and secondary PH (SPH), the presence of IPH was significantly greater in patients with elevated PIC levels than in those with normal levels (25.7 vs 5.1%, P<0.02). CONCLUSIONS: These results suggest that plasma PIC levels may be a marker of PH, especially IPH, in patients with SSc.  (+info)

Vitamin K--what, why, and when. (54/402)

Policies for giving babies vitamin K prophylactically at birth have been dictated, over the last 60 years, more by what manufacturers decided on commercial grounds to put on the market, than by any informed understanding of what babies actually need, or how it can most easily be given. By a pure fluke a 1 mg IM dose, designed to prevent early vitamin deficiency bleeding ("haemorrhagic disease of the newborn") has been found to protect against late deficiency bleeding-a condition unrecognised at the time this policy took hold. Alternative strategies for oral prophylaxis are now opening up (see pp 109 and 113), but these are also, at the moment, dictated more by what the manufacturers choose to provide than by what would make for ease of delivery either in poor countries, or in the developed world.  (+info)

Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding. (55/402)

OBJECTIVE: To determine whether the use of mixed micellar vitamin K improves the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule. DESIGN: Nationwide active surveillance for vitamin K deficiency bleeding (VKDB) complemented with two surveys on the use of the mixed micellar preparation in hospitals and by paediatricians. SETTING AND PATIENTS: Infants in Germany in 1997-2000. INTERVENTION: Prophylaxis with three oral doses of 2 mg mixed micellar vitamin K. MAIN OUTCOME MEASURE: Confirmed VKDB between day 8 and week 12 and no condition requiring specific vitamin K supplementation known before the onset of bleeding. RESULTS: Twenty nine reports met the case definition: seven had not received any vitamin K prophylaxis; for three, vitamin K prophylaxis was unknown; two had insufficient vitamin K prophylaxis for their age; 17 had been given the recommended doses. The mixed micellar preparation had been given to seven, other preparations to nine, and one had been given both. These cases did not differ with respect to the site of bleeding and cholestasis detected at bleeding. Estimates of the use of the mixed micellar preparation in birth hospitals and by paediatricians yielded 1 817 769 newborns exposed to the mixed micellar preparation and 1 320 926 newborns exposed to other preparations. The rate of late VKDB was 0.44/100 000 (95% confidence interval (CI) 0.19 to 0.87) in children given mixed micellar vitamin K compared with 0.76/100 000 (95% CI 0.36 to 1.39) in children given other preparations. CONCLUSION: Mixed micellar vitamin K did not significantly improve the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.  (+info)

Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding. (56/402)

OBJECTIVE: To compare the pharmacokinetics and efficacy of oral versus intravenous mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease, a known risk factor for vitamin K deficiency bleeding. DESIGN: Prospective randomised controlled study. SETTING: Paediatric Liver Unit. PATIENTS: Forty four infants less than 6 months of age with conjugated hyperbilirubinaemia. MAIN OUTCOME MEASURES: Serum concentrations of vitamin K(1) and undercarboxylated prothrombin (PIVKA-II; a sensitive functional indicator of vitamin K status) before and for up to four days after a single dose of mixed micellar K(1) 1 mg intravenously or 2 mg orally. Comparison of K(1) levels 24 hours after oral K(1) with those from 14 healthy newborns given the same dose. RESULTS: At admission, 18 infants (41%) had elevated levels of serum PIVKA-II and eight (18%) had low K(1) concentrations, indicative of subclinical vitamin K deficiency. Median serum K(1) concentrations were similar in the oral and intravenous groups at baseline (0.92 v 1.15 ng/ml), rising to 139 ng/ml six hours after intravenous K(1) but to only 1.4 ng/ml after oral administration. In the latter group, the low median value (0.95 ng/ml) and wide range (< 0.15-111 ng/ml) of serum K(1) compared unfavourably with the much higher levels (median 77, range 11-263 ng/ml) observed in healthy infants given the same oral dose, and suggested impaired and erratic intestinal absorption in cholestatic infants. The severity of malabsorption was such that only 4/24 (17%) achieved an incremental rise in serum K(1) > 10 ng/ml. CONCLUSIONS: The intestinal absorption of mixed micellar K(1) is unreliable in infants with conjugated hyperbilirubinaemia. Given the strong association between cholestasis and late vitamin K deficiency bleeding, these data provide an explanation for the failure of some oral vitamin K(1) prophylaxis regimens in infants with latent cholestasis.  (+info)