Effect of antiplatelet therapy on thromboembolism after flow diversion with the Pipeline Embolization Device

Clinical article

View More View Less
  • 1 Cerebrovascular and Endovascular Division, Department of Neurosurgery, and
  • 2 Department of Radiology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object

Flow-diverting stents offer a novel treatment approach to intracranial aneurysms. Data regarding the incidence of acute procedure-related thromboembolic complications following deployment of the Pipeline Embolization Device (PED) remain scant. The authors sought to determine the rate of embolic events in a bid to identify potential risk factors and assess the role of platelet inhibition.

Methods

Data in all patients receiving a PED for treatment of an intracranial aneurysm were prospectively maintained in a database. Diffusion-weighted 3-T MRI was performed within 24 hours of PED deployment. The incident rate of procedural embolism was established, and univariate analysis was then performed to determine any associations of embolic events with measured variables. The degree of platelet inhibition in response to aspirin and clopidogrel was evaluated by challenging the platelet samples with arachidonic acid and adenosine diphosphate, respectively, and then performing formal light transmission platelet aggregometry.

Results

Twenty-three patients with 26 aneurysms were eligible for inclusion in the study. Thirty-one PEDs were deployed in 25 procedures. All ischemic lesions detected on diffusion-weighted 3-T MRI were identified as embolic based on their location and distribution, with none appearing to be due to perforator artery occlusion. Procedural embolic events were found in the target parent vessel territory in 13 (52%) of 25 procedures, with no patients harboring lesions contralateral to the deployed PED. The number of embolic events per procedure ranged from 3 to 16, with a mean of 5.4. There was no significant difference between cases with and without procedural embolism in platelet inhibition by aspirin (mean 15% vs 12% residual activation; p = 0.28), platelet inhibition by clopidogrel (mean 41% vs 41% residual activation; p = 0.98), or intraprocedural heparin-induced anticoagulation (mean activated clotting time 235 seconds vs 237 seconds; p = 0.81). By multivariate analysis, the authors identified larger aneurysm size (p = 0.03) as the single variable significantly associated with procedural embolism. There was no significant relationship between aneurysm size and the number of embolic events (p = 0.32) or the total burden of the embolism lesion area (p = 0.53).

Conclusions

Acute embolism following use of the PED for treatment of intracranial aneurysms is more common than hypothesized. The only identifiable risk factor for embolism appears to be greater aneurysm size, perhaps indicating significant disturbed flow across the aneurysm neck with ingress and egress through the PED struts. The strength of antiplatelet therapy, as measured by residual platelet aggregation, did not appear to be associated with cases of procedural embolism. Further work is needed to determine the implications of these findings and whether anticoagulation regimens can be altered to lower the rate of complications following PED deployment.

Abbreviations used in this paper:ACT = activated clotting time; ADP = adenosine diphosphate; ICA = internal carotid artery; LTA = light transmission aggregometry; PED = Pipeline Embolization Device; PRU = P2Y12 reaction units.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address correspondence to: Adel M. Malek, M.D., Ph.D., Department of Neurosurgery, Tufts Medical Center, 800 Washington St., Boston, MA 02111. email: amalek@tuftsmedicalcenter.org.

Please include this information when citing this paper: published online August 23, 2013; DOI: 10.3171/2013.7.JNS122178.

  • 1

    Bendszus M, , Koltzenburg M, , Burger R, , Warmuth-Metz M, , Hofmann E, & Solymosi L: Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet 354:15941597, 1999

    • Search Google Scholar
    • Export Citation
  • 2

    Bidet A, , Jais C, , Puymirat E, , Coste P, , Nurden A, & Jakubowski J, : VerifyNow and VASP phosphorylation assays give similar results for patients receiving clopidogrel, but they do not always correlate with platelet aggregation. Platelets 21:94100, 2010

    • Search Google Scholar
    • Export Citation
  • 3

    Blais N, , Pharand C, , Lordkipanidzé M, , Sia YK, , Merhi Y, & Diodati JG: Response to aspirin in healthy individuals. Crosscomparison of light transmission aggregometry, VerifyNow system, platelet count drop, thromboelastography (TEG) and urinary 11-dehydrothromboxane B(2). Thromb Haemost 102:404411, 2009

    • Search Google Scholar
    • Export Citation
  • 4

    Breet NJ, , van Werkum JW, , Bouman HJ, , Kelder JC, , Ruven HJ, & Bal ET, : Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 303:754762, 2010

    • Search Google Scholar
    • Export Citation
  • 5

    Briganti F, , Napoli M, , Tortora F, , Solari D, , Bergui M, & Boccardi E, : Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with periprocedural complications—a retrospective data analysis. Neuroradiology 54:11451152, 2012

    • Search Google Scholar
    • Export Citation
  • 6

    D'Urso PI, , Lanzino G, , Cloft HJ, & Kallmes DF: Flow diversion for intracranial aneurysms: a review. Stroke 42:23632368, 2011

  • 7

    De Miguel A, , Ibanez B, & Badimón JJ: Clinical implications of clopidogrel resistance. Thromb Haemost 100:196203, 2008

  • 8

    Delgado Almandoz JE, , Crandall BM, , Scholz JM, , Fease JL, , Anderson RE, & Kadkhodayan Y, : Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline Embolization Device. J Neurointerv Surg [epub ahead of print], 2013

    • Search Google Scholar
    • Export Citation
  • 9

    Fiorella D, , Woo HH, , Albuquerque FC, & Nelson PK: Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the pipeline embolization device. Neurosurgery 62:11151121, 2008

    • Search Google Scholar
    • Export Citation
  • 10

    Fischer S, , Vajda Z, , Aguilar Perez M, , Schmid E, , Hopf N, & Bäzner H, : Pipeline embolization device (PED) for neurovascular reconstruction: initial experience in the treatment of 101 intracranial aneurysms and dissections. Neuroradiology 54:369382, 2012

    • Search Google Scholar
    • Export Citation
  • 11

    Gaglia MA, , Torguson R, , Pakala R, , Xue Z, , Sardi G, & Suddath WO, : Correlation between light transmission aggregometry, VerifyNow P2Y12, and VASP-P platelet reactivity assays following percutaneous coronary intervention. J Interv Cardiol 24:529534, 2011

    • Search Google Scholar
    • Export Citation
  • 12

    Grove EL, , Hvas AM, , Johnsen HL, , Hedegaard SS, , Pedersen SB, & Mortensen J, : A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease. Thromb Haemost 103:12451253, 2010

    • Search Google Scholar
    • Export Citation
  • 13

    Heller RS, , Miele WR, , Do-Dai DD, & Malek AM: Crescent sign on magnetic resonance angiography revealing incomplete stent apposition: correlation with diffusion-weighted changes in stent-mediated coil embolization of aneurysms. Clinical article. J Neurosurg 115:624632, 2011

    • Search Google Scholar
    • Export Citation
  • 14

    Jakubowski JA, , Li YG, , Small DS, , Payne CD, , Tomlin ME, & Luo J, : A comparison of the VerifyNow P2Y12 point-of-care device and light transmission aggregometry to monitor platelet function with prasugrel and clopidogrel: an integrated analysis. J Cardiovasc Pharmacol 56:2937, 2010

    • Search Google Scholar
    • Export Citation
  • 15

    Kallmes DF, , Ding YH, , Dai D, , Kadirvel R, , Lewis DA, & Cloft HJ: A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 38:23462352, 2007

    • Search Google Scholar
    • Export Citation
  • 16

    Kallmes DF, , Ding YH, , Dai D, , Kadirvel R, , Lewis DA, & Cloft HJ: A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 30:11531158, 2009

    • Search Google Scholar
    • Export Citation
  • 17

    Kan P, , Siddiqui AH, , Veznedaroglu E, , Liebman KM, , Binning MJ, & Dumont TM, : Early postmarket results after treatment of intracranial aneurysms with the pipeline embolization device: a U.S. multicenter experience. Neurosurgery 71:10801088, 2012

    • Search Google Scholar
    • Export Citation
  • 18

    Lylyk P, , Miranda C, , Ceratto R, , Ferrario A, , Scrivano E, & Luna HR, : Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery 64:632643, 2009

    • Search Google Scholar
    • Export Citation
  • 19

    Madsen EH, , Saw J, , Kristensen SR, , Schmidt EB, , Pittendreigh C, & Maurer-Spurej E: Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention. Clin Chem 56:839847, 2010

    • Search Google Scholar
    • Export Citation
  • 20

    McAuliffe W, , Wycoco V, , Rice H, , Phatouros C, , Singh TJ, & Wenderoth J: Immediate and midterm results following treatment of unruptured intracranial aneurysms with the pipeline embolization device. AJNR Am J Neuroradiol 33:164170, 2012

    • Search Google Scholar
    • Export Citation
  • 21

    Nelson PK, , Lylyk P, , Szikora I, , Wetzel SG, , Wanke I, & Fiorella D: The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 32:3440, 2011

    • Search Google Scholar
    • Export Citation
  • 22

    Nesbitt WS, , Westein E, , Tovar-Lopez FJ, , Tolouei E, , Mitchell A, & Fu J, : A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15:665673, 2009

    • Search Google Scholar
    • Export Citation
  • 23

    Phillips TJ, , Wenderoth JD, , Phatouros CC, , Rice H, , Singh TP, & Devilliers L, : Safety of the pipeline embolization device in treatment of posterior circulation aneurysms. AJNR Am J Neuroradiol 33:12251231, 2012

    • Search Google Scholar
    • Export Citation
  • 24

    Price MJ, , Berger PB, , Teirstein PS, , Tanguay JF, , Angiolillo DJ, & Spriggs D, : Standard-vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:10971105, 2011. (Erratum in JAMA 305: 2174, 2011)

    • Search Google Scholar
    • Export Citation
  • 25

    Price MJ, , Endemann S, , Gollapudi RR, , Valencia R, , Stinis CT, & Levisay JP, : Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 29:9921000, 2008

    • Search Google Scholar
    • Export Citation
  • 26

    Puffer RC, , Kallmes DF, , Cloft HJ, & Lanzino G: Patency of the ophthalmic artery after flow diversion treatment of paraclinoid aneurysms. Clinical article. J Neurosurg 116:892896, 2012

    • Search Google Scholar
    • Export Citation
  • 27

    Shobayashi Y, , Tateshima S, , Kakizaki R, , Sudo R, , Tanishita K, & Vinuela F: Intra-aneurysmal hemodynamic alterations by a self-expandable intracranial stent and flow diversion stent: high intra-aneurysmal pressure remains regardless of flow velocity reduction. J Neurointerv Surg [epub ahead of print], 2012

    • Search Google Scholar
    • Export Citation
  • 28

    Szikora I, , Berentei Z, , Kulcsar Z, , Marosfoi M, , Vajda ZS, & Lee W, : Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the pipeline embolization device. AJNR Am J Neuroradiol 31:11391147, 2010

    • Search Google Scholar
    • Export Citation
  • 29

    van Rooij WJ, & Sluzewski M: Perforator infarction after placement of a pipeline flow-diverting stent for an unruptured A1 aneurysm. AJNR Am J Neuroradiol 31:E43E44, 2010

    • Search Google Scholar
    • Export Citation
  • 30

    Velat GJ, , Fargen KM, , Lawson MF, , Hoh BL, , Fiorella D, & Mocco J: Delayed intraparenchymal hemorrhage following pipeline embolization device treatment for a giant recanalized ophthalmic aneurysm. J Neurointerv Surg 4:e24, 2012

    • Search Google Scholar
    • Export Citation
  • 31

    Woo KS, , Kim BR, , Kim JE, , Goh RY, , Yu LH, & Kim MH, : Determination of the prevalence of aspirin and clopidogrel resistances in patients with coronary artery disease by using various platelet-function tests. Korean J Lab Med 30:460468, 2010

    • Search Google Scholar
    • Export Citation
  • 32

    Zimmermann N, & Hohlfeld T: Clinical implications of aspirin resistance. Thromb Haemost 100:379390, 2008

Metrics

All Time Past Year Past 30 Days
Abstract Views 544 343 29
Full Text Views 283 61 6
PDF Downloads 305 60 13
EPUB Downloads 0 0 0