title: Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration. A randomised controlled trial.
abstract: Granulocyte colony-stimulating factor (G-CSF) stimulates the bone marrow to produce granulocytes and stem cells and is widely used to accelerate neutrophil recovery after chemotherapy. Interestingly, specific G-CSF receptors have been demonstrated not only on myeloid cells, but also on platelets. Data on the effects of G-CSF on platelet function are limited and partly conflicting. The objective of this study was to determine the effect of G-CSF on platelet aggregation and in vivo platelet activation. Seventy-eight, healthy volunteers were enrolled into this randomised, placebo-controlled trial. Subjects received 5 μg/kg methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) or placebo subcutaneously for four days. We determined platelet aggregation with a whole blood impedance aggregometer with various, clinically relevant platelet agonists (adenosine diphosphate [ADP], collagen, arachidonic acid [AA], ristocetin and thrombin receptor activating peptide 6 [TRAP]). Filgrastim injection significantly enhanced ADP (+40%), collagen (+60%) and AA (+75%)-induced platelet aggregation (all p<0.01 as compared to placebo and p<0.001 as compared to baseline). In addition, G-CSF enhanced ristocetin-induced platelet aggregation (+18%) whereas TRAP-induced platelet aggregation decreased slightly (-14%) in response to filgrastim. While baseline aggregation with all agonists was only slightly but insignificantly higher in women than in men, this sex difference was enhanced by G-CSF treatment, and became most pronounced for ADP after five days (p<0.001). Enhanced platelet aggregation translated into a 75% increase in platelet activation as measured by circulating soluble P-selectin. G-CSF enhances platelet aggregation and activation in humans. This may put patients suffering from cardiovascular disease and cancer at risk for thrombotic events.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Spiel
authors.forename: Johann
authors.initials: J
authors.lastname: Bartko
authors.forename: Michael
authors.initials: M
authors.lastname: Schwameis
authors.forename: Christa
authors.initials: C
authors.lastname: Firbas
authors.forename: Jolanta
authors.initials: J
authors.lastname: Siller-Matula
authors.forename: Matthias
authors.initials: M
authors.lastname: Schuetz
authors.forename: Manuela
authors.initials: M
authors.lastname: Weigl
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins; D012310:Ristocetin / Q000494:pharmacology; D012737:Sex Factors; D013927:Thrombosis / Q000209:etiology
chemical_list: D019007:P-Selectin; D010446:Peptide Fragments; D011994:Recombinant Proteins; C082835:thrombin receptor peptide (42-47); D012310:Ristocetin; D016179:Granulocyte Colony-Stimulating Factor; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate