Acute thrombus formation on phosphorilcholine surface modified flow diverters

Abstract

PurposeThromboembolic complications remain a limitation of flow diverting stents. We hypothesize that phosphorilcholine surface modified flow diverters (Pipeline Flex with Shield Technology, sPED) would have less acute thrombus formation on the device surface compared with the classic Pipeline Embolization device (cPED).MethodsElastase-induced aneurysms were created in 40 rabbits and randomly assigned to receive cPED or sPED devices with and without dual antiplatelet therapy (DAPT) (four groups, n=10/group). Angioplasty was performed to enhance apposition and create intimal injury for a pro-thrombotic environment. Both before and after angioplasty, the flow diverter was imaged with intravascular optical coherence tomography. The outcome measure was the number of predefined segments along the implant relative to the location of the aneurysm with a minimum of 0 (no clot formation) and maximum of 3 (all segments with thrombus). Clot formation over the device at ostia of branch arteries was assessed as either present or absent.ResultsFollowing angioplasty, the number of flow diverter segments with clots was significantly associated with the flow diverter (p<0.0001), but not with DAPT (p=0.3872) or aneurysm neck size (p=0.8555). The incidence rate for clots with cPED was 1.72 times more than with sPED. The clots on the flow diverter at the location corresponding to side branch ostia was significantly lower with sPED than with cPED (OR 0.180; 95% CI 0.044 to 0.734; p=0.0168), but was not associated with DAPT (p=0.3198).ConclusionIn the rabbit model, phosphorilcholine surface modified flow diverters are associated with less thrombus formation on the surface of the device.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model

“…We demonstrate that Pipeline Shield has the lowest thrombogenicity of all devices tested and is statistically comparable to negative control for TAT and βTG measurements. This additionally confirms our prior findings regarding the non-thrombogenic profile of Pipeline Shield with reference to platelet and fibrin adhesion to the device surface ex vivo 10 and in vivo 11 as well as reduced thrombin generation in vitro. 9 The combined effects of material and flow induced thrombogenicity becomes more apparent for dual-layer devices such as FRED, where separation between the two layers could potentially create a nidus for entrapment and growth of thrombus.…”

“…Species wide coagulation profile differences are apparent from previous reports . The result in showing reduced thrombogenicity with Shield Technology in this study with freshly drawn human blood and previous studies in nonhuman primate and rabbits confirm the hypothesis that although species wide differences in coagulation may exist, the overall thrombogenicity differences between Pipeline Shield and other flow diverter devices are clearly evident.…”

“…The device has a 3 nm phosphorylcholine‐based surface modification (Shield Technology™) that is covalently bound to the braid surface. The surface treatment imparts a non‐thrombogenic and biomimetic surface that has also been shown to reduce inflammation and increase early neointimal growth in preclinical studies, in addition to reducing material thrombogenicity and thrombus formation in several studies—in vitro, ex vivo, and in vivo . This is supplemented by recent clinical data supporting the safety of Pipeline Shield with no major stroke or neurological death at 30 days follow‐up .…”

Phosphorylcholine surface modified flow diverter associated with reduced intimal hyperplasia

“…The Pipeline embolization device with phosphorylcholine surface modification was recently developed in order to improve the hemocompatibility of this device, and reduced thrombogenicity has been demonstrated both in vitro3 and vivo 4. This surface modification has already demonstrated efficacy in reducing NIH on arterial grafts 5…”

“…Phosphorylcholine surface modified flow diverters (Pipeline Flex with Shield Technology, sPED) were recently developed and demonstrated reduced thrombogenicity both in vitro3 and vivo 4. We hypothesized that the improved thrombogenicity profile of the sPED5 may be associated with reduced NIH.…”