title: Mechanisms in endocrinology: The spectrum of haemostatic abnormalities in glucocorticoid excess and defect.
abstract: Glucocorticoids (GCs) target several components of the integrated system that preserves vascular integrity and free blood flow. Cohort studies on Cushing's syndrome (CS) have revealed increased thromboembolism, but the pathogenesis remains unclear. Lessons from epidemiological data and post-treatment normalisation time suggest a bimodal action with a rapid and reversible effect on coagulation factors and an indirect sustained effect on the vessel wall. The redundancy of the steps that are potentially involved requires a systematic comparison of data from patients with endogenous or exogenous hypercortisolism in the context of either inflammatory or non-inflammatory disorders. A predominant alteration in the intrinsic pathway that includes a remarkable rise in factor VIII and von Willebrand factor (vWF) levels and a reduction in activated partial thromboplastin time appears in the majority of studies on endogenous CS. There may also be a rise in platelets, thromboxane B2, thrombin-antithrombin complexes and fibrinogen (FBG) levels and, above all, impaired fibrinolytic capacity. The increased activation of coagulation inhibitors seems to be compensatory in order to counteract disseminated coagulation, but there remains a net change towards an increased risk of venous thromboembolism (VTE). Conversely, GC administered in the presence of inflammation lowers vWF and FBG, but fibrinolytic activity is also reduced. As a result, the overall risk of VTE is increased in long-term users. Finally, no studies have assessed haemostatic abnormalities in patients with Addison's disease, although these may present as a consequence of bilateral adrenal haemorrhage, especially in the presence of antiphospholipid antibodies or anticoagulant treatments. The present review aimed to provide a comprehensive overview of the complex alterations produced by GCs in order to develop better screening and prevention strategies against bleeding and thrombosis.
authors.affiliation: Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK andrea.isidori@uniroma1.it ashley.grossman@ocdem.ox.ac.uk.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Isidori
authors.affiliation: Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Minnetti
authors.affiliation: Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK.
authors.forename: Emilia
authors.initials: E
authors.lastname: Sbardella
authors.affiliation: Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Graziadio
authors.affiliation: Department of Experimental MedicineSapienza University of Rome, Viale del Policlinico 155, Rome 00161, ItalyOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7LE, UK andrea.isidori@uniroma1.it ashley.grossman@ocdem.ox.ac.uk.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
mesh_terms: D001778:Blood Coagulation Disorders / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D003480:Cushing Syndrome / Q000150:complications / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005938:Glucocorticoids / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D013922:Thrombocytosis / Q000209:etiology / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D014841:von Willebrand Factor; D013929:Thromboxane B2; D005169:Factor VIII; D005340:Fibrinogen