A prospective study of G-CSF effects on hemostasis in allogeneic blood stem cell donors

Granulocyte colony-stimulating factor (G-CSF) is used in healthy donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. However, some data have recently suggested that G-CSF may induce a hypercoagulable state, prompting us to study prospectively 22 PBSC donors before and after G-CSF 5 mu g/kg twice daily. We sought evidence for changes in the followin g parameters: platelet count, von Willebrand factor antigen (vWF:Ag) and ac tivity (vWF activity), beta-thromboglobulin (beta-TG), platelet factor 4 (P F-4), platelet activation markers (GMP-140 and PAC-1), activated partial th romboplastin time (aPTT), prothrombin time (PT), coagulant factor Vm (FVIII :C), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), thrombomodulin (TM) and tissue plasminogen activator antigen (tPA:Ag) prior to G-CSF and immediately before leukapheresis, ADP-induced platelet aggreg ation studies were also performed. G-CSF administration produced only mild discomfort. We found a significant increase in vWF:Ag (from 0.99 +/- 0.32 U /ml to 1.83 +/- 0.69 U/ml; P < 0.001), in vWF activity (from 1.04 +/- 0.34 U/ml to 1.78 +/- 0.50 U/ml; P < 0.001) and in FVIII:C (from 1.12 +/- 0.37 U /ml to 1.73 +/- 0.57 U/ml; P < 0.001) after G-CSF, Of note, four donors wit h low baseline VWF had a two- to three-fold increase after receiving G-CSF, G-CSF had no impact on the platelet count, beta-TG, PF-4, GMP-140 or PAC-1 , The final% of platelet aggregation decreased from 73 +/- 22% to 37 +/- 26 % after G-CSF (P < 0.001), We found a significant decrease in aPTT after G- CSF (29.9 +/- 3.1 s to 28.3 +/- 3.3 s; P = 0.004), but the PT was unaffecte d. In addition, we also observed a significant increase in TAT, F1+2 and TM , but not in tPA:Ag, Our data suggest that G-CSF may possibly induce a hype rcoagulable state by increasing levels of FVIII:C and thrombin generation, In contrast to this information, we found reduced platelet aggregation afte r G-CSF administration, The clinical implications of these findings remain unclear and larger studies are definitely required.