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.