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

Abstract

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 μg/kg twice daily. We sought evidence for changes in the following parameters: platelet count, von Willebrand factor antigen (vWF:Ag) and activity (vWF activity), β-thromboglobulin (β-TG), platelet factor 4 (PF-4), platelet activation markers (GMP-140 and PAC-1), activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulant factor VIII (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 aggregation 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 with low baseline vwf had a two- to three-fold increase after receiving g-csf. g-csf had no impact on the platelet count, β-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 unaffected. 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 hypercoagulable state by increasing levels of FVIII:C and thrombin generation. In contrast to this information, we found reduced platelet aggregation after G-CSF administration. The clinical implications of these findings remain unclear and larger studies are definitely required.