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 × 10⁶/ml vs. 67.45 × 10⁶/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10⁶/ml vs. 26.31 × 10⁶/ml; p = 0.05), monocytes (51.31 × 10⁶/ml vs. 9.03 × 10⁶/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10⁶/ml vs. 0.27 × 10⁶/ml; p = 0.0058), endothelium (49.42 × 10⁶/ml vs. 7.23 × 10⁶/ml; p = 0.007) and endothelium with TF (1.42 × 10⁶/ml vs. 0.26 × 10⁶/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. © 2014 S. Karger AG, Basel

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

“…There are conflicting reports on the effect of hydroxyurea on total, specific blood cell-derived and TF-bearing microparticles (31,78,91,173). A reduction in plasma D-dimer level in patients treated with hydroxyurea has been reported (78,174), with these studies reporting conflicting effects of hydroxyurea on circulating TAT complexes. Adult patients treated with hydroxyurea also manifest a longer lag time, slower rate and reduced peak of ex vivo thrombin generation in TGA compared with untreated patients (31).…”

Decrease of externalized phosphatidylserine density on red blood cell‐derived microparticles in SCA patients treated with hydroxycarbamide

“…We and others have previously described reduced plasma concentration of MPs originating from red blood cells (RBC) and platelets in HC‐treated patients (Westerman et al , ; Nébor et al , ; Tantawy et al , ). Two other studies detected increased levels of MPs in treated patients (Brunetta et al , ; Piccin et al , ) while another report did not observe MP concentration variation in HC treated‐patients (Kasar et al , ). Differences in pre‐analytical and analytical procedures, known to significantly affect MP quantification, are unlikely to fully account for these discrepancies as the same procedures were used in the present report and our previous publication (Nébor et al , ).…”

Prothrombotic aspects of sickle cell disease

“…Sickle patients have increased plasma levels of TF-positive MPs [22], derived from endothelial cells and monocytes [86,93,94]. However, two other studies did not detect MMPs [87] or increased MPTF activity in sickle patients compared to controls [42].…”