title: Adverse effects of glucocorticoids: coagulopathy.
abstract: Hypercortisolism is associated with various systemic manifestations, including central obesity, arterial hypertension, glucose intolerance/diabetes mellitus, dyslipidemia, nephrolithiasis, osteoporosis, gonadal dysfunction, susceptibility to infections, psychiatric disorders, and hypercoagulability. The activation of the hemostatic system contributes to the development of atherosclerosis and subsequent cardiovascular morbidity and mortality. Previous studies have identified an increased risk of both unprovoked and postoperative thromboembolic events in patients with endogenous and exogenous Cushing's syndrome (CS). The risk for postoperative venous thromboembolism in endogenous CS is comparable to the risk after total hip or knee replacement under short-term prophylaxis. The mechanisms that are involved in the thromboembolic complications in hypercortisolism include endothelial dysfunction, hypercoagulability, and stasis (Virchow's triad). It seems that at least two factors from Virchow's triad must be present for the occurrence of a thrombotic event in these patients. Most studies have demonstrated that this hypercoagulable state is explained by increased levels of procoagulant factors, mainly factors VIII, IX, and von Willebrand factor, and also by an impaired fibrinolytic capacity, which mainly results from an elevation in plasminogen activator inhibitor 1. Consequently, there is a shortening of activated partial thromboplastin time and increased thrombin generation. For these reasons, anticoagulant prophylaxis might be considered in patients with CS whenever they have concomitant prothrombotic risk factors. However, multicenter studies are needed to determine which patients will benefit from anticoagulant therapy and the dose and time of anticoagulation.
authors.affiliation: Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil.
authors.forename: Maria Caroline Alves
authors.initials: MC
authors.lastname: Coelho
authors.affiliation: Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil.
authors.forename: Camila Vicente
authors.initials: CV
authors.lastname: Santos
authors.affiliation: Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vieira Neto
authors.affiliation: Neuroendocrinology Research Center/Endocrinology SectionMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundo, Rio de Janeiro 21941-913, BrazilEndocrine SectionHospital Pedro Ernesto, Rio de Janeiro, BrazilEndocrine SectionInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, BrazilEndocrine SectionHospital Federal da Lagoa, Rio de Janeiro, Brazil mgadelha@hucff.ufrj.br.
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D003480:Cushing Syndrome / Q000150:complications / Q000378:metabolism*; D005164:Factor IX / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019851:Thrombophilia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D054556:Venous Thromboembolism / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D005169:Factor VIII; D005164:Factor IX