Thrombogenicity of flow diverters in an ex vivo shunt model

Effect of phosphorylcholine surface modification

Matthew W. Hagen, Gaurav Girdhar, John Wainwright, Monica Hinds

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 fibrindriven thrombogenicity associated with FRED relative to PED.

Original languageEnglish (US)
Pages (from-to)1006-1011
Number of pages6
JournalJournal of NeuroInterventional Surgery
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2017

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Phosphorylcholine
Equipment and Supplies
Blood Platelets
Technology
clopidogrel
Therapeutics
Fibrin
Aspirin

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Thrombogenicity of flow diverters in an ex vivo shunt model : Effect of phosphorylcholine surface modification. / Hagen, Matthew W.; Girdhar, Gaurav; Wainwright, John; Hinds, Monica.

In: Journal of NeuroInterventional Surgery, Vol. 9, No. 10, 01.10.2017, p. 1006-1011.

Research output: Contribution to journalArticle

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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 fibrindriven thrombogenicity associated with FRED relative to PED.",
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AU - Hinds, Monica

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N2 - 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 fibrindriven thrombogenicity associated with FRED relative to PED.

AB - 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 fibrindriven thrombogenicity associated with FRED relative to PED.

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