title: Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia.
abstract: Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 10(6)/ml vs. 67.45 × 10(6)/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10(6)/ml vs. 26.31 × 10(6)/ml; p = 0.05), monocytes (51.31 × 10(6)/ml vs. 9.03 × 10(6)/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10(6)/ml vs. 0.27 × 10(6)/ml; p = 0.0058), endothelium (49.42 × 10(6)/ml vs. 7.23 × 10(6)/ml; p = 0.007) and endothelium with TF (1.42 × 10(6)/ml vs. 0.26 × 10(6)/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.
authors.affiliation: Center for Cell-Based Therapy, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Denise Menezes
authors.initials: DM
authors.lastname: Brunetta
authors.forename: Gil Cunha
authors.initials: GC
authors.lastname: De Santis
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Silva-Pinto
authors.forename: Luciana Correa
authors.initials: LC
authors.lastname: Oliveira de Oliveira
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000986:Antisickling Agents / Q000008:administration & dosage*; D000991:Antithrombins / Q000097:blood; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D008297:Male; D008534:Megaloblasts / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D013925:Thromboplastin / Q000096:biosynthesis
chemical_list: D000986:Antisickling Agents; D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D013925:Thromboplastin; D006918:Hydroxyurea