Effects of FX06 In Vitro on Platelet, Coagulation, and Fibrinolytic Biomarkers in Volunteers and Patients With Documented Coronary Artery Disease
Autor: | Jonas Hallén, Dan Atar, Victor L. Serebruany |
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Rok vydání: | 2014 |
Předmět: |
Adult
Blood Platelets Male Ticlopidine Platelet Aggregation medicine.medical_treatment Coronary Artery Disease In Vitro Techniques Pharmacology Fibrin Fibrinogen Degradation Products Coronary artery disease Young Adult Von Willebrand factor Fibrinolysis Humans Medicine Pharmacology (medical) Platelet Blood Coagulation Hemostasis Aspirin Dose-Response Relationship Drug biology business.industry General Medicine Middle Aged medicine.disease Clopidogrel Peptide Fragments Coagulation Case-Control Studies biology.protein Female business Biomarkers Platelet Aggregation Inhibitors medicine.drug |
Zdroj: | American Journal of Therapeutics. 21:91-98 |
ISSN: | 1075-2765 |
Popis: | 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. |
Databáze: | OpenAIRE |
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