Effects of rhG-CSF Plus Dexamethasone on Hemostatic Parameters in Healthy Granulocyte Donors: Role of u-PA and Nitric Oxide

Abstract

Granulocyte colony-stimulating factor (G-CSF) is widely used to reduce the risk of infection resulting from neutropenias and to mobilize and collect CD34+ hematopoetic progenitor cells (HPCs) for autologous and allogenic transplantation. The safety of recombinant human G-CSF (rhG-CSF) administration in healthy donors has been investigated in several studies. However, there are limited cumulative data about the effects of rhG-CSF on hemostasis. Hemostatic parameters, including, urokinase-type plasminogen activator antigen (u-pA:Ag) and nitric oxide in 17 healthy granulocyte apheresis donors who donated for neutropenic patients were evaluated. rhG-CSF (sing le dose, 10 mu g/kg subcutaneously) and dexamethasone (8 mg, single dose oral) were given to donors 12 hours before granulocyte apheresis. Two blood samples were drawn at time 0 (TO) before rhG-CSF and dexamethasone administration and at timne 1 (T1), immediately before the apheresis. A statistically significant rise in coagulant factor VIII (FVIII) and von Willebrand factor (vWF), and slightly rise in u-PA:Ag were observed after G-CSF plus dexamethasone administration. In addition, there were positive correlations between vWF-D-dimer and FVIII-D-dimer. A significant decrease in mean total nitric oxide (NOx), nitrite, and nitrate levels was also found after G-CSF plus dexamethasone administration. Moreover, there was a strong negative correlation between nitrite and D-dimer levels (r = -0.611; P = .009). Even if partially compensated with u-PA and protein C, increased FVIII and vWF activity, and decreased nitric oxide levels may still partially contribute to progress of thrombosis risk in rhG-CSF plus dexamethasone administered healthy granulocyte donors. Large numbers of healthy donors exposed to G-CSF Plus dexamethasone will be needed to evaluate the risk of thrombosis in this Population.