Outcomes and Risks of Granulocyte Colony-Stimulating Factor in Patients With Coronary Artery Disease

Abstract

Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.

Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis

“…Studies have reported endothelial cell dysfunction, clotting activation, an increase in blood oxidative status, platelet aggregation, and neutrophil activation in healthy donors during treatment with G-CSF (31,44). Despite this, most of the G-CSF-treated healthy subjects do not experience thrombotic events (13,44,45), and G-CSF is considered a safe mobilizing agent. The prothrombotic effects that have been associated with G-CSF have been linked to its use in the treatment of inflammatory or already-prothrombotic states, such as acute myocardial infarction, through mobilization of autologous stem cells (45,46).…”

“…Despite this, most of the G-CSF-treated healthy subjects do not experience thrombotic events (13,44,45), and G-CSF is considered a safe mobilizing agent. The prothrombotic effects that have been associated with G-CSF have been linked to its use in the treatment of inflammatory or already-prothrombotic states, such as acute myocardial infarction, through mobilization of autologous stem cells (45,46). This is in accordance with our results suggesting that, in the presence of G-CSF, neutrophils may be more sensitive to NET formation, in particular, upon encountering a "second hit," such as low-grade infection.…”

Granulocyte Colony Stimulating Factor in the Treatment of Cardiac Ischemic Disease. A Decade has Passed: Is it Time to Give Up?

“…Encouraged by pre-clinical data, the first clinical trials to evaluate the feasibility and safety of G-CSF appeared in 2004/2005. G-CSF was utilized to mobilize stem cells and/or treat patients after percutaneous coronary intervention (PCI) [22][23][24] and confirmed that this new type of treatment could be tested with a minimum of security, although some adverse effects were proposed [25].…”

“…1b). Initially, as requested, clinical investigations were performed with a limited number of patients, with or without a placebo group and in an openlabel or single-blind design [22][23][24][25][26][27]. All confirmed the safety and feasibility of G-CSF treatment.…”

“…We cannot exclude the possible negative effect of a large fibrotic tissue production reported by others [19] after G-CSF injections since scar tissue could reduce the conduction of electrical impulse and promote the re-entry of arrhythmic events. In clinical trials, although there are few reports of adverse effects like incidence of re-stenosis and coronary neointima growth [25], phase I/II studies with G-CSF administration after MI and percutaneous coronary intervention (reperfusion) demonstrated that this approach is feasible and safe. Furthermore, G-CSF neither enhanced nor diminished ventricular arrhythmia.…”