Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Platelets. 2010;21(6):464-9. doi: 10.3109/09537104.2010.485255.
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.
粒细胞集落刺激因子（G-CSF）已被证明可诱导患者和外周血干细胞供者出现高凝状态。有趣的是，目前关于 G-CSF 对血小板和凝血激活的动力学的数据很少，并且尚不清楚 G-CSF 是否增强剪切依赖性血小板功能。本研究旨在探讨这两个问题。本研究共纳入 36 名健康志愿者。所有受试者均单次静脉注射 5μg/kg 非格司亭。通过血小板功能分析仪 PFA-100（胶原/肾上腺素（CEPI-CT）、胶原/ADP（CADP-CT）闭合时间）、血管性血友病因子活性（vWF：RiCO）ELISA、循环白细胞组织因子（TF）-mRNA 表达和旋转血栓弹性图（ROTEM）评估重组 G-CSF 对血小板和凝血功能的影响。G-CSF 呈时间依赖性增强剪切依赖性血小板功能，PFA-100：CEPI-CT 在 24 小时后下降 48%，CADP-CT 下降 31%，最低值（与基线相比，p<0.001），72 小时后接近基线值。相应地，vWF：RiCO 在 24 小时后增加 59%（p<0.001），48 小时后恢复至基线值。TF-mRNA 在 4 小时后达到峰值（增加 6 倍以上，p<0.001），24 小时后接近基线值。最低闭合时间出现在 24 小时后（-15%；p<0.001）。单次给予 5μg/kg G-CSF 可显著增强剪切依赖性血小板功能，并强烈诱导白细胞 TF-mRNA，导致体外凝血时间缩短。
