Effects of rhG-CSF plus dexamethasone on hemostatic parameters in healthy granulocyte donors: role of u-PA and nitric oxide.
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.
Department of Pediatric Hematology and Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Ozlem Balci
OB
Ekmekçi
Gülyüz
G
Oztürk
Hakan
H
Ekmekçi
Didem
D
Atay
Melek
M
Yanaşik
Sema
S
Anak
Omer
O
Devecioğlu
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001781:Blood Component Removal / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005169:Factor VIII / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006098:Granulocytes / Q000637:transplantation*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D011994:Recombinant Proteins; D012306:Risk; D013927:Thrombosis; D014019:Tissue Donors; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000187:drug effects; D014841:von Willebrand Factor / Q000187:drug effects
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; C036309:fibrin fragment D; D014841:von Willebrand Factor; D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D003907:Dexamethasone; D005169:Factor VIII; D014568:Urokinase-Type Plasminogen Activator