Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study. Antifibrinolytic therapy in recent onset subarachnoid hemorrhage. (41/402)

In this cooperative study among 13 institutions, 502 patients were treated with antifibrinolytic medication (epsilon-aminocaproic acid or tranexamic acid) within a 14-day period following rupture of an intracranial aneurysm. Mortality at the end of 14 days was 11.6%; proved rebleed rate was 12.7%. Patients with an internal carotid or anterior cerebral aneurysm had the highest mortality and rebleed rate. Most rebleeds occurred between the sixth and eleventh days following the initial bleed. Significantly higher mortality was reported among patients with cerebral vasospasm, yet rebleed rate was no different among those patients with or without vasospasm. The same pattern was observed among patients with a mean blood pressure value above and below 110 mm Hg. We conclude that antifibrinolytic therapy provides beneficial treatment to patients with recent onset subarachnoid hemorrhage (SAH) following rupture of an intracranial aneurysm.  (+info)

Changes in peritoneal coagulation and fibrinolysis after discontinuation of chronic peritoneal dialysis. (42/402)

OBJECTIVES: To study changes in peritoneal function after transfer from chronic peritoneal dialysis (CPD) to hemodialysis (HD), especially the effects on peritoneal coagulation, fibrinolytic markers, and mesothelium. DESIGN: Prospective observational study. SETTING: A tertiary-care university hospital. PATIENTS: Nine patients who transferred from CPD to HD were enrolled in the study after giving fully informed consent. METHODS: After transfer to HD, the peritoneal cavity was lavaged with low glucose PD solution once per day through PD catheters left in place. Thrombin-antithrombin III complex (TAT) was measured serially as a marker of peritoneal coagulation. As fibrinolytic markers, fibrinogen/fibrin degradation products (FDP) and plasmin-alpha2-antiplasmin complex (PIC) were assessed. Cancer antigen 125 (CA125) was measured as a marker of mesothelial cell mass. RESULTS: Levels of peritoneal TAT and FDP were much higher than plasma levels, indicating high local fibrin turnover. Transfer to HD induced a significant fall in mean peritoneal TAT, from 115.8 +/- 52.1 to 60.7 +/- 21.8 ng/mL, p < 0.05. Except for 1 patient with a 20-fold increase, mean peritoneal FDP decreased significantly, from 43.6 +/- 11.1 to 19.6 +/- 3.5 microg/mL, p < 0.05. Mean peritoneal PIC increased significantly, from 1.9 +/- 0.4 to 3.9 +/- 0.6 microg/mL, p < 0.05. Peritoneal CA125 increased from 156.4 +/- 57.3 to 1426.2 +/- 389.4 U/mL, p < 0.05. CONCLUSIONS: Peritoneal fibrin turnover was accelerated on CPD and stabilized after transfer to HD. Transfer to HD also induced mesothelial regeneration.  (+info)

Dietary and nondietary determinants of vitamin K biochemical measures in men and women. (43/402)

Few epidemiological studies that rely on the food frequency questionnaire (FFQ) for dietary assessment have measured biomarkers of vitamin K intake to independently confirm associations between self-reported dietary vitamin K intake and disease risk. Associations were examined between two sensitive biomarkers of vitamin K status, plasma phylloquinone and serum percent undercarboxylated osteocalcin (%ucOC), and self-reported usual phylloquinone intake as estimated from a FFQ. The influence of other dietary and nondietary factors on plasma phylloquinone concentrations was also examined. Dietary phylloquinone intake was estimated using a FFQ in 369 men and 468 women of the Framingham Offspring Study. The prevalence of high %ucOC concentrations (>/= 20%), suggestive of a low vitamin K status, was 44% in men and 54% in women, respectively. After multivariate adjustment, the odds of a high %ucOC was 2.5 greater for women (odds ratio: 2.5; 95% confidence interval [CI]: 1.2-5.1) and almost three times greater for men (odds ratio: 2.8; 95% CI: 1.3-5.9) in the lowest dietary phylloquinone intake quintile category compared to the highest quintile category. Fasting triglyceride concentrations, smoking status and season were associated with plasma phylloquinone concentrations, independent of dietary phylloquinone intake. Phylloquinone and green vegetable intake was linearly associated with plasma phylloquinone, after adjustment for potential confounding factors. There were limitations in the use of the FFQ to predict plasma phylloquinone, evident in an observed plateau effect and required nondietary adjustment factors. Despite these caveats, these findings support the use of a FFQ for a relative assessment of vitamin K status in population-based studies.  (+info)

Enhanced activation of bound plasminogen on Staphylococcus aureus by staphylokinase. (44/402)

Activation of plasminogen (plg) to plasmin by the staphylococcal activator, staphylokinase (SAK), is effectively regulated by the circulating inhibitor, alpha2-antiplasmin (alpha2AP). Here it is demonstrated that intact Staphylococcus aureus cells and solubilized staphylococcal cell wall proteins not only protected SAK-promoted plg activation against the inhibitory effect of alpha2AP but also enhanced the activation. The findings suggest that the surface-associated plg activation by SAK may have an important physiological function in helping staphylococci in tissue dissemination. Amino acid sequencing of tryptic peptides originating from the 59-, 56- and 43-kDa proteins, isolated as putative plg-binding proteins, identified them as staphylococcal inosine 5'-monophosphate dehydrogenase, alpha-enolase, and ribonucleotide reductase subunit 2, respectively.  (+info)

The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study. (45/402)

OBJECTIVE: To determine if the use of an antifibrinolytic agent (epsilon aminocaproic acid [EACA]) decreased perioperative and postoperative blood loss in patients who underwent total hip arthroplasty (THA). DESIGN: A prospective, double-blind, randomized, controlled clinical trial. SETTING: A university-affiliated tertiary care hospital with a large joint arthroplasty population. PARTICIPANTS: Fifty-five patients who were scheduled for a primary THA. METHOD: Patients were randomly assigned to 2 groups to receive either EACA or saline placebo perioperatively. Preoperatively, the groups were similar with respect to gender, mean age, mean hemoglobin level, operative time and prosthesis type. OUTCOME MEASURES: Blood loss from the start of surgery until the Hemovac drain was removed, and the transfusion rate and hemoglobin levels. RESULTS: Mean (and standard error) total blood loss for patients receiving EACA was 867 (207) mL and for patients receiving placebo was 1198 (544) mL (p < 0.025). Four patients in the EACA group received 7 units of packed red blood cells and 7 patients in the saline group required 12 units. CONCLUSIONS: Patients receiving the placebo sustained greater total blood loss than EACA patients and were more likely to require blood transfusion. In the current climate of concern over blood transfusions during surgery, EACA administration can reduce blood loss and consequently transfusion and transfusion-related risk.  (+info)

Pharmacokinetics of tranexamic acid during cardiopulmonary bypass. (46/402)

BACKGROUND: Tranexamic acid (TA) reduces blood loss and blood transfusion during heart surgery with cardiopulmonary bypass (CPB). TA dosing has been empiric because only limited pharmacokinetic studies have been reported, and CPB effects have not been characterized. We hypothesized that many of the published TA dosing techniques would prove, with pharmacokinetic modeling and simulation, to yield unstable TA concentrations. METHODS: Thirty adult patients undergoing elective coronary artery bypass grafting, valve surgery, or repair of atrial septal defect received after induction of anesthesia: TA 50 mg/kg (n = 11), TA 100 mg/kg (n = 10), or TA 10 mg/kg (n = 10) over 15 min, with 1 mg x kg(-1) x hr(-1) maintenance infusion for 10 h. TA was measured in plasma using high performance liquid chromatography. Pharmacokinetic modeling was accomplished using a mixed effects technique. Models of increasing complexity were compared using Schwarz-Bayesian Criterion (SBC). RESULTS: Tranexamic acid concentrations rapidly fell in all three groups. Data were well fit to a 2-compartment model, and adjustments for CPB were supported by SBC. Assuming a body weight of 80 kg, our model estimates V1 = 10.3 l before CPB and 11.9 l during and after CPB; V2 = 8.5 l before CPB and 9.8 l during and after CPB; Cl1 = 0.15 l/s before CPB, 0.11 l/s during CPB, and 0.17 l/s after CPB; and Cl2 = 0.18 l/s before CPB and 0.21 l/s during and after CPB. Based on simulation of previous studies of TA efficacy, we estimate that a 30-min loading dose of 12.5 mg/kg with a maintenance infusion of 6.5 mg x kg(-1) x hr(-1) and 1 mg/kg added to the pump prime will maintain TA concentration greater than 334 microm, and a higher dose based on 30 mg/kg loading dose plus 16 mg x kg(-1) x h(-1) continuous infusion and 2 mg/kg added to the pump prime would maintain TA concentrations greater than 800 microm. CONCLUSIONS: Tranexamic acid pharmacokinetics are influenced by CPB. Our TA pharmacokinetic model does not provide support for the wide range of TA dosing techniques that have been reported. Variation in TA efficacy from study to study and confusion about the optimal duration of TA treatment may be the result of dosing techniques that do not maintain stable, therapeutic TA concentrations.  (+info)

Normal D-dimer levels in emergency department patients suspected of acute pulmonary embolism. (47/402)

OBJECTIVES: We sought to determine:1) whether normal D-dimer enzyme-linked immunosorbent assay (ELISA) assays predicted the absence of pulmonary embolism (PE) in the high-volume emergency department (ED) of the Brigham and Women's Hospital, and 2) whether ED physicians accepted normal D-dimer levels as confirmation of no PE without further diagnostic testing such as lung scanning, chest computed tomography (CT) scanning, or pulmonary angiography. BACKGROUND: Although the plasma D-dimer ELISA is a sensitive screening test for excluding acute PE, this laboratory marker has not been widely integrated into clinical algorithms such as creatine kinase-MB fraction or troponin testing for acute myocardial infarction. METHODS: We mandated that ED physicians order D-dimer ELISA tests on all patients suspected of acute PE. We reviewed the clinical record of each ED patient initially evaluated for suspected PE during the year 2000. We determined whether additional imaging tests for PE were obtained and whether the final diagnosis was PE. RESULTS: Of 1,106 D-dimer assays, 559 were elevated and 547 were normal. Only 2 of 547 had PE despite a normal D-dimer. The sensitivity of the D-dimer ELISA for acute PE was 96.4% (95% confidence interval [CI]: 87.5% to 99.6%), and the negative predictive value was 99.6% (95% CI: 98.7% to >99.9%). Nevertheless, 24% of patients with normal D-dimers had additional imaging tests for PE. CONCLUSIONS: The D-dimer ELISA has a high negative predictive value for excluding PE. By paying more attention to normal D-dimer results, fewer chest CT scans and lung scans will be required, and improvements may be realized in diagnostic efficiency and cost reduction.  (+info)

Aspirin and mortality from coronary bypass surgery. (48/402)

BACKGROUND: There is no therapy known to reduce the risk of complications or death after coronary bypass surgery. Because platelet activation constitutes a pivotal mechanism for injury in patients with atherosclerosis, we assessed whether early treatment with aspirin could improve survival after coronary bypass surgery. METHODS: At 70 centers in 17 countries, we prospectively studied 5065 patients undergoing coronary bypass surgery, of whom 5022 survived the first 48 hours after surgery. We gathered data on 7500 variables per patient and adjudicated outcomes centrally. The primary focus was to discern the relation between early aspirin use and fatal and nonfatal outcomes. RESULTS: During hospitalization, 164 patients died (3.2 percent), and 812 others (16.0 percent) had nonfatal cardiac, cerebral, renal, or gastrointestinal ischemic complications. Among patients who received aspirin (up to 650 mg) within 48 hours after revascularization, subsequent mortality was 1.3 percent (40 of 2999 patients), as compared with 4.0 percent among those who did not receive aspirin during this period (81 of 2023, P<0.001). Aspirin therapy was associated with a 48 percent reduction in the incidence of myocardial infarction (2.8 percent vs. 5.4 percent, P<0.001), a 50 percent reduction in the incidence of stroke (1.3 percent vs. 2.6 percent, P=0.01), a 74 percent reduction in the incidence of renal failure (0.9 percent vs. 3.4 percent, P<0.001), and a 62 percent reduction in the incidence of bowel infarction (0.3 percent vs. 0.8 percent, P=0.01). Multivariate analysis showed that no other factor or medication was independently associated with reduced rates of these outcomes and that the risk of hemorrhage, gastritis, infection, or impaired wound healing was not increased with aspirin use (odds ratio for these adverse events, 0.63; 95 percent confidence interval, 0.54 to 0.74). CONCLUSIONS: Early use of aspirin after coronary bypass surgery is safe and is associated with a reduced risk of death and ischemic complications involving the heart, brain, kidneys, and gastrointestinal tract.  (+info)