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Thromb Haemost 2011; 105(04): 655-662
DOI: 10.1160/TH10-08-0530
Platelets and Blood Cells
Schattauer GmbH

Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration

A randomised controlled trial
Alexander O. Spiel
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
2   Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
,
Johann Bartko
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Michael Schwameis
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Christa Firbas
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Jolanta Siller-Matula
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Matthias Schuetz
3   Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
,
Manuela Weigl
4   Department of Anaesthesiology, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria
,
Bernd Jilma
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received: 16 August 2010

Accepted after major revision: 25 January 2011

Publication Date:
28 November 2017 (online)

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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-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.

Keywords

G-CSF - platelets - whole blood aggregometry - randomised controlled trial - gender difference
 

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