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In-vitro thrombogenicity assessment of flow diversion and aneurysm bridging devices

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Abstract

Endoluminal devices such as metallic flow diversion (FD) and aneurysm bridging (AB) stents are used for treatment of intracranial aneurysms. Treatments are associated with thrombogenic events mandating the use of dual antiplatelet therapy in all cases. In the current in vitro study, we utilize a slow binding fluorogenic thrombin specific substrate to measure the thrombin generation potential of six devices: four FD devices (Pipeline™ Flex embolization device, Pipeline™ Flex embolization device with Shield Technology™, SILK+, FRED™) and two AB devices (Solitaire™ AB, LEO+). We show that the Pipeline™ Flex embolization device with Shield Technology™ has significantly lower peak thrombin and takes significantly longer time to achieve peak thrombin (time to peak) compared to the other three FD devices (p < 0.05), with statistically similar results to the less thrombogenic AB devices. We conclude that surface modification of endoluminal stents could be an effective method to mitigate thrombogenic complications.

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References

  1. Starke RM, Turk A, Ding D, Crowley RW, Liu KC, Chalouhi N, Hasan DM, Dumont AS, Jabbour P, Durst CR, Turner RD (2014) Technology developments in endovascular treatment of intracranial aneurysms. J Neurointerv Surg. doi:10.1136/neurintsurg-2014-011475

    Google Scholar 

  2. Zuckerman SL, Eli IM, Morone PJ, Dewan MC, Mocco J (2014) Novel technologies in the treatment of intracranial aneurysms. Neurol Res 36(4):368–382. doi:10.1179/1743132814y.0000000318

    Article  PubMed  Google Scholar 

  3. Alderazi YJ, Shastri D, Kass-Hout T, Prestigiacomo CJ, Gandhi CD (2014) Flow diverters for intracranial aneurysms. Stroke Res Treat 2014:415653. doi:10.1155/2014/415653

    PubMed Central  PubMed  Google Scholar 

  4. Jeong HW, Seo JH, Kim ST, Jung CK, Suh SI (2014) Clinical practice guideline for the management of intracranial aneurysms. Neurointervention 9(2):63–71. doi:10.5469/neuroint.2014.9.2.63

    Article  PubMed Central  PubMed  Google Scholar 

  5. Rahme RJ, Zammar SG, El Ahmadieh TY, El Tecle NE, Ansari SA, Bendok BR (2014) The role of antiplatelet therapy in aneurysm coiling. Neurol Res 36(4):383–388. doi:10.1179/1743132814y.0000000317

    Article  CAS  PubMed  Google Scholar 

  6. Murayama Y, Nien YL, Duckwiler G, Gobin YP, Jahan R, Frazee J, Martin N, Vinuela F (2003) Guglielmi detachable coil embolization of cerebral aneurysms: 11 years’ experience. J Neurosurg 98(5):959–966. doi:10.3171/jns.2003.98.5.0959

    Article  PubMed  Google Scholar 

  7. Kallmes DF, Hanel R, Lopes D, Boccardi E, Bonafe A, Cekirge S, Fiorella D, Jabbour P, Levy E, McDougall C, Siddiqui A, Szikora I, Woo H, Albuquerque F, Bozorgchami H, Dashti SR, Delgado Almandoz JE, Kelly ME, Turner R, Woodward BK, Brinjikji W, Lanzino G, Lylyk P (2015) International retrospective study of the pipeline embolization device: a multicenter aneurysm treatment study. Am J Neuroradiol 36(1):108–115. doi:10.3174/ajnr.A4111

    Article  CAS  PubMed  Google Scholar 

  8. Shapiro M, Becske T, Sahlein D, Babb J, Nelson PK (2012) Stent-supported aneurysm coiling: a literature survey of treatment and follow-up. Am J Neuroradiol 33(1):159–163. doi:10.3174/ajnr.A2719

    Article  CAS  PubMed  Google Scholar 

  9. Becske T, Kallmes DF, Saatci I, McDougall CG, Szikora I, Lanzino G, Moran CJ, Woo HH, Lopes DK, Berez AL, Cher DJ, Siddiqui AH, Levy EI, Albuquerque FC, Fiorella DJ, Berentei Z, Marosfoi M, Cekirge SH, Nelson PK (2013) Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 267(3):858–868. doi:10.1148/radiol.13120099

    Article  PubMed  Google Scholar 

  10. Lewis AL, Stratford PW (2002) Phosphorylcholine-coated stents. J Long Term Eff Med Implants 12(4):231–250

    Article  CAS  PubMed  Google Scholar 

  11. Whelan DM, van der Giessen WJ, Krabbendam SC, van Vliet EA, Verdouw PD, Serruys PW, van Beusekom HM (2000) Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries. Heart 83(3):338–345

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Kuiper KK, Robinson KA, Chronos NA, Cui J, Palmer SJ, Nordrehaug JE (1998) Phosphorylcholine-coated metallic stents in rabbit iliac and porcine coronary arteries. Scand Cardiovasc J 32(5):261–268

    Article  CAS  PubMed  Google Scholar 

  13. Chen C, Lumsden AB, Ofenloch JC, Noe B, Campbell EJ, Stratford PW, Yianni YP, Taylor AS, Hanson SR (1997) Phosphorylcholine coating of ePTFE grafts reduces neointimal hyperplasia in canine model. Ann Vasc Surg 11(1):74–79. doi:10.1007/s100169900013

    Article  CAS  PubMed  Google Scholar 

  14. Besser M, Baglin C, Luddington R, van Hylckama Vlieg A, Baglin T (2008) High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 6(10):1720–1725. doi:10.1111/j.1538-7836.2008.03117.x

    Article  CAS  PubMed  Google Scholar 

  15. Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA (2006) Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 296(4):397–402. doi:10.1001/jama.296.4.397

    Article  CAS  PubMed  Google Scholar 

  16. van Hylckama Vlieg A, Christiansen SC, Luddington R, Cannegieter SC, Rosendaal FR, Baglin TP (2007) Elevated endogenous thrombin potential is associated with an increased risk of a first deep venous thrombosis but not with the risk of recurrence. Br J Haematol 138(6):769–774. doi:10.1111/j.1365-2141.2007.06738.x

    Article  Google Scholar 

  17. Chandler WL, Roshal M (2009) Optimization of plasma fluorogenic thrombin-generation assays. Am J Clin Pathol 132(2):169–179. doi:10.1309/AJCP6AY4HTRAAJFQ

    Article  CAS  PubMed  Google Scholar 

  18. Hemker HC, Beguin S (1995) Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 74(1):134–138

    CAS  PubMed  Google Scholar 

  19. Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Beguin S (2003) Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 33(1):4–15

    Article  CAS  PubMed  Google Scholar 

  20. Hemker HC, Willems GM, Beguin S (1986) A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemost 56(1):9–17

    CAS  PubMed  Google Scholar 

  21. Girdhar G, Read M, Sohn J, Shah C, Shrivastava S (2014) In-vitro thrombogenicity assessment of polymer filament modified and native platinum embolic coils. J Neurol Sci 339(1–2):97–101. doi:10.1016/j.jns.2014.01.030

    Article  CAS  PubMed  Google Scholar 

  22. Young G, Sorensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS (2013) Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood 121(11):1944–1950. doi:10.1182/blood-2012-08-378935

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D (2011) The pipeline embolization device for the intracranial treatment of aneurysms trial. Am J Neuroradiol 32(1):34–40. doi:10.3174/ajnr.A2421

    CAS  PubMed  Google Scholar 

  24. Krischek O, Miloslavski E, Fischer S, Shrivastava S, Henkes H (2011) A comparison of functional and physical properties of self-expanding intracranial stents [Neuroform3, Wingspan, Solitaire, Leo+, Enterprise]. Minim Invasive Neurosurg 54(1):21–28. doi:10.1055/s-0031-1271681

    Article  CAS  PubMed  Google Scholar 

  25. Heller RS, Dandamudi V, Lanfranchi M, Malek AM (2013) Effect of antiplatelet therapy on thromboembolism after flow diversion with the pipeline embolization device. J Neurosurg 119(6):1603–1610. doi:10.3171/2013.7.jns122178

    Article  PubMed  Google Scholar 

  26. Delgado Almandoz JE, Crandall BM, Scholz JM, Fease JL, Anderson RE, Kadkhodayan Y, Tubman DE (2014) Last-recorded P2Y12 reaction units value is strongly associated with thromboembolic and hemorrhagic complications occurring up to 6 months after treatment in patients with cerebral aneurysms treated with the pipeline embolization device. Am J Neuroradiol 35(1):128–135. doi:10.3174/ajnr.A3621

    Article  CAS  PubMed  Google Scholar 

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Compliance with ethical standards

This study was funded through a contract with Medtronic plc. Gaurav Girdhar, Junwei Li and John Wainwright all are employed by Medtronic plc. Wayne Chandler has full control of all primary data and agrees to allow the journal to review the data if requested.

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Correspondence to Wayne L. Chandler.

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Girdhar, G., Li, J., Kostousov, L. et al. In-vitro thrombogenicity assessment of flow diversion and aneurysm bridging devices. J Thromb Thrombolysis 40, 437–443 (2015). https://doi.org/10.1007/s11239-015-1228-0

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  • DOI: https://doi.org/10.1007/s11239-015-1228-0

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