Effects of FX06 In vitro on platelet, coagulation, and fibrinolytic biomarkers in volunteers and patientswith documented coronary artery disease

Jonas Hallén, Dan Atar, Victor Serebruany

Research output: Contribution to journalArticle

Abstract

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 preincubation 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 dosedependent 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.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalAmerican Journal of Therapeutics
Volume21
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Coagulation
  • Fibrin-derived peptide
  • Fibrinolysis
  • FX06
  • Platelets
  • Reperfusion injury
  • ST-elevation myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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