Platelets and Blood Cells
© Schattauer 2011
Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration A randomised controlled trial Alexander O. Spiel1,2; Johann Bartko1; Michael Schwameis1; Christa Firbas1; Jolanta Siller-Matula1; Matthias Schuetz3; Manuela Weigl4; Bernd Jilma1 1Department
of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; 2Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria; of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; 4Department of Anaesthesiology, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria
3Department
Summary 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-metHuGCSF, 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 pla-
Correspondence to: Bernd Jilma, MD Medical University of Vienna Department of Clinical Pharmacology Waehringer Guertel 18–20, 1090 Vienna, Austria Tel.: +43 1 40400 2981, Fax: +43 1 40400 2998 E-mail:
[email protected]
Introduction Granulocyte colony-stimulating factor (G-CSF) is used for the treatment of neutropenic patients as well as the collection of peripheral blood stem cells. G-CSF stimulates the proliferation of the precursor cells specific to the granulocytic lineage and augments their functional activities (1–3). Specific G-CSF receptors have been demonstrated on myeloid cells, but also on platelets (4). Shimoda et al. identified high affinity platelet G-CSF receptors and demonstrated that G-CSF preincubation is able to augment adenosine diphosphate (ADP) -induced platelet aggregation. Two other studies (5, 6) found increased collagen- and ADP-induced platelet aggregation after ex vivo incubation with G-CSF. However, data on the in vivo effects of G-CSF on platelet function are limited
telet aggregation (all p
