Effects of rhG-CSF plus dexamethasone on hemostatic parameters in healthy granulocyte donors: role of u-PA and nitric oxide

Clin Appl Thromb Hemost. 2009 Dec;15(6):689-94. doi: 10.1177/1076029608320720. Epub 2008 Jun 10.

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 (single dose, 10 microg/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 (T(0)) before rhG-CSF and dexamethasone administration and at time 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Blood Component Removal / methods
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Drug Therapy, Combination
  • Factor VIII / drug effects
  • Fibrin Fibrinogen Degradation Products / drug effects
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocytes / transplantation*
  • Hemostasis / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / blood
  • Recombinant Proteins
  • Risk
  • Thrombosis
  • Tissue Donors
  • Urokinase-Type Plasminogen Activator / blood
  • Urokinase-Type Plasminogen Activator / drug effects
  • von Willebrand Factor / drug effects

Substances

  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Recombinant Proteins
  • fibrin fragment D
  • von Willebrand Factor
  • Granulocyte Colony-Stimulating Factor
  • Nitric Oxide
  • Dexamethasone
  • Factor VIII
  • Urokinase-Type Plasminogen Activator