Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination

Abstract

Summary:Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen. Keywords: in vitro bleeding test; blood coagulation; recombinant human granulocyte colony-stimulating factor; transcranial Doppler ultrasound In the context of autologous and allogeneic stem cell transplantation rhG-CSF is routinely used as a growth factor to mobilize peripheral blood stem cells. 1,2 In patients with normal bone marrow function this leads to a significant increase of peripheral leukocyte counts, so that rheological changes and disturbances of blood flow are to be anticipated. To date, we have noted thrombotic complications of central venous lines in two out of 20 patients under rhG-CSF administration. Moreover, in vitro tests demonstrated an activation of platelets and the coagulation system. 3,4 As a growing number of healthy donors receive rhG-CSF for stem cell mobilization in our institution, we were interested

Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation – laboratory and clinical evidence

“…However, an in vitro model in support of these results demonstrated an induction of plasminogen activator in G-CSF stimulated endothelial cells [16]. Unlike in this study, slightly reduced protein C in healthy volunteers on G-CSF treatment has been recently reported [21]. As noted above, effects of marked neutrophilia on coagulation are conceivable and may yield an explanation.…”

“…G-CSF has been associated with increased platelet activation [1] and aggregation [11] as well as with elevated markers of endothelium or coagulation activation [6]. Söhngen et al [21] reported a shortening of bleeding time, and increased levels of fibrinogen and factor VIII, but reduced activities of proteins C and S in healthy volunteers. Similar results were found by Kuroiwa et al [17].…”

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

“…Leblanc et al [23] found increased levels of Factor VIII:C and thrombin generation in normal donors after rhG-CSF administration. Söhngen et al [26] detected increased Factor VIII and fibrinogen levels, while protein C and protein S activities were reduced. These data suggest that rhG-CSF may induce a transient prothrombotic or hypercoagulable state in some normal donors.…”

Granulocyte-Colony–Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke

“…[7][8][9] G-CSF does not appear to induce platelet aggregation or microembolism. 10,11 In experimental models of stroke (in mice and rats), G-CSF exhibited neuroprotective and regenerative activity, including recruiting neural progenitor cells, reducing cerebral edema, improving survival, and enhancing sensorimotor and functional recovery. [12][13][14][15][16][17][18] This multimodal behavior of G-CSF means that it is a candidate treatment for enhancing recovery after stroke, although no clinical studies addressing this treatment paradigm have been reported to date.…”