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

Area of Science:

• Hematology
• Pharmacology
• Thrombosis Research

Background:

• Granulocyte colony-stimulating factor (G-CSF) is linked to hypercoagulability in patients and stem cell donors.
• Limited data exist on G-CSF's impact on platelet and coagulation kinetics, particularly shear-dependent platelet function.

Purpose of the Study:

• To investigate the time-dependent effects of a single G-CSF dose on platelet activation and coagulation.
• To determine if G-CSF augments shear-dependent platelet function.

Main Methods:

• Thirty-six healthy volunteers received a single intravenous dose of filgrastim (5 microg/kg).
• Assessed platelet function (PFA-100: CEPI-CT, CADP-CT), von Willebrand factor activity (vWF:RiCO), leukocyte tissue factor mRNA expression, and rotation thrombelastography (ROTEM).

Main Results:

• G-CSF significantly enhanced shear-dependent platelet function, with closure times decreasing by 48% (CEPI-CT) and 31% (CADP-CT) at 24 hours (p < 0.001).
• von Willebrand factor activity increased by 59% (p < 0.001) at 24 hours.
• Leukocyte tissue factor mRNA peaked at 4 hours (>6-fold increase, p < 0.001).
• Ex vivo clotting times were shortened, indicating enhanced coagulation.

Conclusions:

• Single-dose G-CSF administration significantly enhances shear-dependent platelet function and induces leukocyte tissue factor mRNA expression.
• These effects translate into shortened ex vivo clotting times, suggesting a transient hypercoagulable state.
• Further research is warranted to understand the clinical implications in patients and donors receiving G-CSF.