Journal of Thrombosis and Thrombolysis

, Volume 40, Issue 4, pp 437–443 | Cite as

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

  • Gaurav Girdhar
  • Junwei Li
  • Larisa Kostousov
  • John Wainwright
  • Wayne L. Chandler


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.


Thrombin generation Flow diversion devices Aneurysm bridging devices 


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.


  1. 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. 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 CrossRefPubMedGoogle Scholar
  3. 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 PubMedCentralPubMedGoogle Scholar
  4. 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 PubMedCentralCrossRefPubMedGoogle Scholar
  5. 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 CrossRefPubMedGoogle Scholar
  6. 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 CrossRefPubMedGoogle Scholar
  7. 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 CrossRefPubMedGoogle Scholar
  8. 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 CrossRefPubMedGoogle Scholar
  9. 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 CrossRefPubMedGoogle Scholar
  10. 10.
    Lewis AL, Stratford PW (2002) Phosphorylcholine-coated stents. J Long Term Eff Med Implants 12(4):231–250CrossRefPubMedGoogle Scholar
  11. 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):338–345PubMedCentralCrossRefPubMedGoogle Scholar
  12. 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):261–268CrossRefPubMedGoogle Scholar
  13. 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 CrossRefPubMedGoogle Scholar
  14. 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 CrossRefPubMedGoogle Scholar
  15. 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 CrossRefPubMedGoogle Scholar
  16. 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 CrossRefGoogle Scholar
  17. 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 CrossRefPubMedGoogle Scholar
  18. 18.
    Hemker HC, Beguin S (1995) Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 74(1):134–138PubMedGoogle Scholar
  19. 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):4–15CrossRefPubMedGoogle Scholar
  20. 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):9–17PubMedGoogle Scholar
  21. 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 CrossRefPubMedGoogle Scholar
  22. 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 PubMedCentralCrossRefPubMedGoogle Scholar
  23. 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 PubMedGoogle Scholar
  24. 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 CrossRefPubMedGoogle Scholar
  25. 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 CrossRefPubMedGoogle Scholar
  26. 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 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gaurav Girdhar
    • 1
  • Junwei Li
    • 2
  • Larisa Kostousov
    • 3
  • John Wainwright
    • 2
  • Wayne L. Chandler
    • 4
  1. 1.Venous Vascular R&DMedtronicMansfieldUSA
  2. 2.Neurovascular R&DMedtronicIrvineUSA
  3. 3.Houston Methodist HospitalHoustonUSA
  4. 4.Department of LaboratoriesSeattle Children’s HospitalSeattleUSA

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