Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers.

OBJECTIVE: Increased circulating levels of hemostatic factors have been associated with arterial and venous thrombosis. Although in vitro evidence suggests that glucocorticoids may activate hemostasis and inhibit thrombolysis, no controlled in vivo studies have examined the effects of glucocorticoids on hemostatic factors. We hypothesized that a 5-day treatment course of dexamethasone would increase circulating levels of hemostatic and anti-fibrinolytic factors. METHODS: We randomized 24 healthy men ages 19-39 to receive either dexamethasone 3 mg twice daily versus placebo for 5 days. Parameters examined before and after the intervention included: clotting factors VII, VIII, and XI, von Willebrand factor (vWF), D-dimer, PAI-1, soluble CD40-ligand (sCD40-ligand), and fibrinogen. RESULTS: Dexamethasone tended to modestly increase clotting factors levels and fibrinogen without significantly affecting PAI-1, D-dimer or sCD40-ligand. Factor VII increased by a mean of 13% (p = 0.04 versus placebo), factor VIII by 27% (p = 0.0008), factor XI by 6% (p = 0.01), and fibrinogen by 13% (p = 0.05). CONCLUSIONS: Glucocorticoids may increase the activity of clotting factors in vivo. This may contribute to the reported increased risk of thrombosis in patients with sustained exposure to glucocorticoids.

Effects of short-term glucocorticoids on cardiovascular biomarkers.

CONTEXT: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized. OBJECTIVE: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. DESIGN: We conducted a randomized, double-blind, placebo-controlled study. SETTING: The study took place in a tertiary care hospital. STUDY SUBJECTS: Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study. INTERVENTION: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. MEASURES: Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state. RESULTS: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. CONCLUSIONS: Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.

Direct dialysis quantification: investigation of the impact of dialysate preservation techniques on solute assays.

AIMS: Urease-producing microorganisms may lower urea nitrogen (UN) during dialysate-side dosing. We investigated the impact of 3 proven preservatives (acetic acid, ceftazidime, thimerosal) on UN concentration, and the concentrations of creatinine (CR) and beta2-microglobulin (beta2M). METHODS: The UN, CR and beta2M concentrations were assayed in 3 separate aliquots from 20 spent dialysate samples (ceftazidime, 125 mg/l, or 1% thimerosal, 1 ml/l, vs. control). The beta2M concentration was assayed in 10 further spent dialysate collections (concentrated glacial acetic acid, 5 ml/l, vs. control). Solute concentrations were compared with the concordance correlation coefficient (rc). RESULTS: Ceftazidime and thimerosal had little effect on the concentrations of UN and CR (rc >0.97). For the beta2M concentration, agreement remained good (rc >0.96) for ceftazidime and thimerosal (although the former tended to lower concentrations) but acetic acid was less optimal (rc = 0.893). CONCLUSIONS: Ceftazidime and thimerosal may be used as dialysate preservatives without affecting the UN or CR concentrations. Thimerosal is to be preferred when studying beta2M. Acetic acid produces unacceptable inaccuracy when measuring beta2M.