title: Thrombogenicity of flow diverters in an ex vivo shunt model: effect of phosphorylcholine surface modification.
abstract: BACKGROUND
  Flow diverters offer a promising treatment for cerebral aneurysms. However, they have associated thromboembolic risks, mandating chronic dual antiplatelet therapy (DAPT). Shield Technology is a phosphorylcholine surface modification of the Pipeline Embolization Device (PED) flow diverter, which has shown significant reductions in material thrombogenicity in vitro.
  
  
  OBJECTIVE
  To compare the thrombogenicity of PED, PED with Shield Technology (PED+Shield), and the Flow-Redirection Endoluminal Device (FRED)-with and without single antiplatelet therapy and DAPT-under physiological flow.
  
  
  METHODS
  An established non-human primate ex vivo arteriovenous shunt model of stent thrombosis was used. PED, PED+Shield, and FRED were tested without antiplatelet therapy, with acetylsalicylic acid (ASA) monotherapy, and with DAPT. Radiolabeled platelet deposition was quantified over 1 hour for each device and total fibrin deposition was also quantified.
  
  
  RESULTS
  Cumulative statistical analysis showed significantly lower platelet deposition on PED compared with FRED. The same statistical model showed significant decreases in platelet deposition when ASA, clopidogrel, or Shield Technology was used. Direct comparisons of device performances within antiplatelet conditions showed consistent significant decreases in platelet accumulation on PED+Shield relative to FRED. PED+Shield showed significant reductions in platelet deposition compared with unmodified PED without antiplatelet therapy and with DAPT. PED accumulated minimal fibrin with and without Shield Technology.
  
  
  CONCLUSIONS
  In this preclinical model, we have shown that the Shield Technology phosphorylcholine modification reduces the platelet-specific thrombogenicity of a flow diverter under physiologically relevant flow with and without DAPT. We have further identified increased fibrin-driven thrombogenicity associated with FRED relative to PED.
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA.
authors: Matthew W
authors: http://orcid.org/0000-0002-9812-2262
authors: MW
authors: Hagen
authors: Neurovascular R&D, Medtronic, Irvine, California, USA.
authors: Gaurav
authors: G
authors: Girdhar
authors: Neurovascular R&D, Medtronic, Irvine, California, USA.
authors: John
authors: J
authors: Wainwright
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA.
authors: Monica T
authors: MT
authors: Hinds
mesh_terms: D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects* / Q000379:methods; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000295:instrumentation*; D002532:Intracranial Aneurysm / Q000097:blood / Q000209:etiology / Q000628:therapy; D020767:Intracranial Thrombosis / Q000097:blood / Q000209:etiology / Q000628:therapy*; D008297:Male; D048530:Papio anubis; D010767:Phosphorylcholine; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D015607:Stents; D013499:Surface Properties; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D010767:Phosphorylcholine; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aneurysm; Flow Diverter; Platelets; Stenosis; Technology