FX06 is a naturally occurring
fibrin-derived
peptide demonstrated to confer cytoprotection in the setting of primary
percutaneous coronary intervention. Because the effect of FX06 on human platelet, coagulation, and fibrinolysis
biomarkers (PCFB) is unknown but is important for further clinical development, we evaluated how FX06 affects PCFB. The in vitro effects of the whole-blood pre-incubation with escalating concentrations of FX06 (4, 25, and 75 μg/mL) were assessed in
aspirin-naïve healthy volunteers (n = 10), those with multiple risk factors for
vascular disease (n = 10), and patients with documented
coronary artery disease (n = 10). The last two groups were treated with
aspirin (81 mg/daily). Thirty-two variables of PCFB were measured with the vehicle and for each chosen FX06 dose. Pretreatment of blood samples with FX06 resulted in a moderate but significant and mostly dose-dependent increases of platelet aggregation induced by
adenosine diphosphate and
collagen. Similarly, the closure time was reduced, suggesting share-induced activation,
PECAM-1, GP Ib,
GP IIb/IIIa activity, and
vitronectin receptors, which were also up-regulated. In contrast,
P-selectin and GPIIb
antigen expression were reduced after FX06. All other PCFB were predominantly unaffected by FX06, with the exception of the increased
plasminogen, decreased
protein C activity, and activated
von Willebrand factor. We conclude that in the therapeutic range, FX06 in vitro mildly affects hemostasis by way of mostly activating platelets. Applying moderate concomitant antiplatelet strategies should be considered for the adequate protection from vascular thrombotic events in patients treated with FX06. Similar ex vivo study in patients receiving
aspirin and
clopidogrel is warranted.