Single dose granulocyte colony-stimulating factor markedly enhances shear-dependent platelet function in humans

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been associated with the induction of a hypercoagulable state in patients as well as peripheral blood stem donors. Interestingly, sparse data exist on the kinetics of platelet and coagulation activation in response to G-CSF and it is unknown if G-CSF augments shear-dependent platelet function. These two issues are addressed in the current trial. Thirty-six healthy volunteers were enrolled into this study. All subjects received a single-dose of 5 µg/kg filgrastim intravenously. The effects of recombinant G-CSF on platelet and coagulation function were assessed by the platelet function analyzer PFA-100 (collagen/epinephrine (CEPI-CT), collagen/ADP (CADP-CT) closure times), von Willebrand factor activity (vWF : RiCO) ELISA, tissue factor (TF)-mRNA expression on circulating leukocytes and rotation thrombelastography (ROTEM). G-CSF time-dependently enhanced shear dependent platelet function measured by the PFA-100: CEPI-CT declined by 48% and CADP-CT by 31% with nadir values after 24 h (p < 0.001 as compared to baseline) and returned to near-baseline values after 72 hours. In accordance, VWF : RiCO increased by 59% after 24 h (p < 0.001) and returned to baseline 48 h later. TF-mRNA peaked after 4 hours (>6 fold increase p < 0.001) and reached near-baseline values after 24 hours. Nadir closure times were seen after 24 hours (−15%; p < 0.001). Single-dose administration of 5 µg/kg G-CSF significantly enhances shear-dependent platelet function and strongly induces leukocyte TF-mRNA, which translates into shortened clotting times ex vivo.

• G-CSF, platelets, vWF:RiCO, thrombelastography, tissue factor