Single dose granulocyte colony-stimulating factor markedly enhances shear-dependent platelet function in humans.
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 microg/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 microg/kg G-CSF significantly enhances shear-dependent platelet function and strongly induces leukocyte TF-mRNA, which translates into shortened clotting times ex vivo.
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Alexander O
AO
Spiel
Jolanta
J
Siller-Matula
Christa
C
Firbas
Judith M
JM
Leitner
Guenter
G
Russmueller
Bernd
B
Jilma
D000328:Adult; D001782:Blood Donors; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D016179:Granulocyte Colony-Stimulating Factor