Administration of granulocyte-colony-stimulating factor for allogeneic hematopoietic cell collection may induce the tissue factor-dependent pathway in healthy donors.
The hypercoagulable state caused by the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been cited in anecdotal reports. Since tissue factor (TF) is the main initiator of the coagulation cascade, we examined if rhG-CSF had an inductive effect on the TF-dependent pathway in 18 healthy donors receiving rhG-CSF (10 microg/kg/day x 5 days) for peripheral blood progenitor cell mobilization. After rhG-CSF, there were increases both in TF antigen (TF:Ag) (P=0.01) and TF procoagulant activity (TF:PCA) (P=0.06) plasma levels and in TF:Ag cytofluorimetric expression on CD33 (+) cells (P=0.04). Mean activities of FVIII and vWF also increased significantly. Thrombin time was slightly prolonged (P=0.06) due to significant increases in plasma D-dimer levels. In addition, while FIX activity remained stable, there were marked reductions in mean plasma FX and FII activities and a slight decrease in FVII activity that resulted in a significant prolongation of prothrombin time within normal ranges. In conclusion, the administration of rhG-CSF led to a "prothrombotic state" via stimulation of TF and increased endothelial markers, such as F VIII and vWF. In the light of these findings, the use of rhG-CSF for stem cell mobilization should be undertaken cautiously in healthy donors with underlying thrombotic risk factors.
Topcuoglu
P
P
Department of Hematology, Ankara University School of Medicine, Ibni Sina Hospital, Sihhiye-Ankara 06100, Turkey.
Arat
M
M
Dalva
K
K
Ozcan
M
M
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D005164:Factor IX / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism; D011994:Recombinant Proteins; D013918:Thrombin Time; D013925:Thromboplastin / Q000378:metabolism*; D014019:Tissue Donors
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D013925:Thromboplastin