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2.
Thromb Res ; 118(2): 247-52, 2006.
Article in English | MEDLINE | ID: mdl-16005496

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Hemostasis/drug effects , Adult , Blood Coagulation/drug effects , Double-Blind Method , Factor VII/metabolism , Factor VIII/metabolism , Factor XI/metabolism , Fasting , Fibrinogen/metabolism , Fibrinolysis/drug effects , Humans , Male
3.
Am J Cardiol ; 95(6): 744-7, 2005 Mar 15.
Article in English | MEDLINE | ID: mdl-15757601

ABSTRACT

The incidence of antiplatelet factor-4/heparin antibody formation in patients who receive contemporary doses of unfractionated heparin in the setting of percutaneous coronary revascularization is unknown. Also unknown is the ability of these antibodies to activate platelets or adversely affect clinical outcome in the absence of clinically recognized heparin-induced thrombocytopenia. To address these questions, we serially measured antiplatelet factor-4/heparin antibody levels and performed serotonin release assays in patients who underwent percutaneous coronary intervention. Correlations were then made across antibody induction, heparin exposure, and clinical outcome at 6 months.


Subject(s)
Angina Pectoris/immunology , Angioplasty, Balloon, Coronary , Antibody Formation/immunology , Coronary Disease/immunology , Heparin/immunology , Myocardial Infarction/immunology , Platelet Factor 4/immunology , Aged , Angina Pectoris/mortality , Angina Pectoris/therapy , Antibody Formation/drug effects , Coronary Disease/mortality , Coronary Disease/therapy , Female , Follow-Up Studies , Heparin/administration & dosage , Heparin/adverse effects , Humans , Immune Complex Diseases/chemically induced , Immune Complex Diseases/immunology , Immune Complex Diseases/mortality , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Platelet Activation/drug effects , Platelet Activation/immunology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/mortality , Recurrence , Risk Factors , Serotonin/blood , Survival Rate
4.
Am J Med ; 114(4): 276-82, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12681454

ABSTRACT

PURPOSE: To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients. METHODS: We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic evaluation for possible venous thromboembolism. We included patients with a history of malignancy, recent surgery, thrombosis, and anticoagulation treatment. C-reactive protein levels were assayed as a measure of inflammation. RESULTS: Of 45 patients with radiographically proven proximal deep venous thrombosis or pulmonary embolism, 43 had elevated D-dimer levels by enzyme-linked immunosorbent assay (ELISA) (sensitivity, 96%); the specificity of the test was 23% (36/157). The qualitative non-ELISA tests had higher specificities, but their sensitivities were <70%. Nineteen patients (42%) with thrombosis had false-negative D-dimer tests by at least one assay. The specificity of the tests decreased with increasing duration of hospitalization, increasing age, and increasing C-reactive protein levels. D-dimer testing had little or no utility in distinguishing patients with thrombosis from those without in patients who had been hospitalized for more than 3 days, were older than 60 years, or had C-reactive protein levels in the highest quartile. CONCLUSION: In unselected inpatients, D-dimer testing has limited clinical utility because of its poor specificity. This is particularly true for older patients, those who have undergone prolonged hospitalization, and those with markedly elevated C-reactive protein levels. In some patient subsets, a negative non-ELISA D-dimer test cannot discriminate between inpatients with and without thrombosis.


Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Pulmonary Embolism/blood , Venous Thrombosis/blood , Adult , Age Factors , Aged , Agglutination Tests , Biomarkers/analysis , Case-Control Studies , Chi-Square Distribution , Enzyme-Linked Immunosorbent Assay , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inpatients , Latex Fixation Tests , Male , Middle Aged , Prognosis , Prospective Studies , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/therapy , ROC Curve , Radiography , Risk Assessment , Sensitivity and Specificity , Statistics, Nonparametric , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/therapy
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