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 microg/kg twice daily. We sought evidence for changes in the following parameters: platelet count, von Willebrand factor antigen (vWF:Ag) and activity (vWF activity), beta-thromboglobulin (beta-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, 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 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.
LeBlanc
R
R
St Sacrement Hospital, Laval University, Quebec City, Quebec, Canada.
Roy
J
J
Demers
C
C
Vu
L
L
Cantin
G
G
D000328:Adult; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D015331:Cohort Studies; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D013917:Thrombin / Q000096:biosynthesis; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000378:metabolism
D011994:Recombinant Proteins; D014841:von Willebrand Factor; D016179:Granulocyte Colony-Stimulating Factor; D005169:Factor VIII; D013917:Thrombin; D000069585:Filgrastim