THE ADMINISTRATION OF GRANULOCYTE COLONY-STIMULATING FACTOR TO HEALTHY DONORS FOR ALLOGENEIC PERIPHERAL BLOOD PROGENITOR CELL COLLECTİON MAY INDUCE THE TISSUE FACTOR DEPENDENT PATHWAY
Abstract
The hypercoagulable state caused by the use of rhG-CSF has been cited in several case reports. Since tissue factor (TF) is the main initlator of the coagulation protease cascade, we examined whether or not rhG-CSF had an inductive effect on the TF-dependent pathway. We reasured plasma TF antigen (TF Ag) and TF
procoagulant activity (TF PCA), TF expression on peripheral biood monocytes and neutrophils and plasma coagulation factor activities in 18 healthy donors (8F/10M; aged 17-52) receiving 10yg/kg/day rhG-CSF for five days in the aim of peripheral blood progenitor cell mobilization. Blood samples were collected before starting G-CSF and on the first day of stem'celi apheresis. There were significant Increases in TF Ag (p<0.05) and TF PCA (p>0.06) levels. Flow cytometric evaluation revealed a significant increase in TF expression on CD33 (4) celis (p-0.04). Mean plasma FVİİİ activity and vWWF activity also increased significantiy. Thrombin time was slightiy prolonged (p-0.06) due to significant increases in plasma D-dimer levels (p<0.05). in addition, while FIX activity remained stable, there were marked decreases in mean plasma FX and Fil activities and a slight decrease in FV activity that resulted in significant prolongation of prothrombin time. The administration of rhG-CSF in healthy stem cell donors increased the mean TF Ag and TF PCA in plasma and TF expression on celis, decreased extrinsic pathway factor activity, increased D-dimer levels and endothelial markers and prolonged PT. in conclusion, the administration of rhG-CSF led to a 'prothrombotic state” via stimulation of TF and increased endothelia| markers such as F Vili and vWF. in light of these findings, the use of rhG-CSF for stem cell mobilization should be undertaken cautiousiy in healthy donors with underiying thrombotic risk factors.
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