The effect of hydroxyurea in the hypercoagulability state of sickle cell disease

• Grant number: 09/16488-7
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2010 - January 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fabíola Traina
• Grantee: Fabíola Traina
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Sickle cell disease is characterized by vaso-occlusive events and intravascular hemolysis, with subsequent nitric oxide depletion, and endothelium dysfunction and activation. Nearly every element of hemostasis, including the endothelium, cellular elements, anticoagulant and the fibrinolytic systems is altered towards the procoagulant state in this disease, and thus, an increased rate of thrombosis is observed. Possible mechanisms involved in this process are: (1) abnormal phosphatidylserine exposure, which serves as a docking site for enzymatic coagulation complexes, (2) alterations of the tissue factor, the physiologic initiator of hemostasis, with an elevation of its total procoagulant activity and expression, (3) increase in the circulating microparticles, derived from various cellular types. A major therapeutic approach in patients with sickle cell disease capable of reducing vaso-occlusive complications and hemolytic anemia is hydroxyurea. This study aims to evaluate the effect of hydroxyurea upon the components of the hemostatic balance in sickle cell disease. To do this we will explore its influence on three of the principal components of hemostasis: (1) tissue factor expression; (2) thrombin generation; (3) endothelium activation. Healthy individuals and sickle cell patients, with and without use of hydroxyurea, will be evaluated and compared. We will measure tissue factor expression using flow cytometry, real time PCR and ELISA; microparticles of different cell origins will be determined through flow cytometry; thrombin antithrombin complex (TAT), prothrombin fragment (F 1+2) and D-dimer (DD) will be measured as markers of thrombin generation; trombomodulin and von Willebrand factor will be determined for evaluation of endothelium activation. (AU)