“Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke

  • Kevin P. Bliden
  • Gabe Raviv
  • Udaya S. Tantry
  • Rahul Chaudhary
  • John W. Cochran
  • Eliano P. Navarese
  • Tricia Brannan
  • Ankit Vyas
  • Paul A. GurbelEmail author


Early assessment of thrombogenicity and antithrombotic drug effects may be important for therapeutic decision making in patients presenting with acute stroke. In this prospective, single center, pilot study, a bedside thrombelastography assay (TEG6s) was used to measure thrombogenicity and antithrombotic drug response in serial patients presenting emergently with symptoms of acute stroke (n = 90). TEG6s measures were compared against diagnosis obtained by NIH Stroke Scale/Score and imaging. Acute ischemic stroke (AIS) was diagnosed in 30 patients, intracerebral hemorrhage (ICH) in 19, transient ischemic attack (TIA) in 10 and stroke mimic (SM) in 31. Patients with AIS had a higher prevalence of A-Fib (33.3% vs. 11.6%, p = 0.01), and ACE inhibitor use (56.3% vs. 21.6%, p < 0.001) compared to combined non-AIS group. Time to initial clot formation (R) was shorter in AIS vs. TIA, ICH, and SM (p < 0.05). Comparing patients with AIS and combined non-AIS group the AUC for R was 0.83 (cut point of ≤ 4.8, sensitivity = 67%; specificity = 84%, p < 0.001). In AIS patients, 46% had suboptimal response (< 30% MAAA inhibition) to aspirin and 80% of patients on P2Y12 therapy had high platelet reactivity (> 50% ADP-induced platelet aggregation). Patients receiving tissue plasminogen activator had significant reduction in clot strength and near complete lysis at 30 min which normalized within 2 h after treatment (p < 0.001 for both). The rapid bedside measurement of thrombogenicity and antithrombotic drug effects is feasible in patients presenting with symptoms of acute stroke. Our preliminary data suggest that AIS is associated with faster ex-vivo clot formation, and poor antiplatelet response. Future study of the TEG6s to “blueprint” hemostasis is warranted in the stroke population.


Stroke Point-of-care Thrombelastography Hemostasis Thrombosis Platelet function test Antiplatelet therapy Anticoagulation therapy 


Author contributions

KPB, GR, UST, JWC, TB, PAG: concept and design. KPB, UST, RC, AV, EPN, PAG: analysis and/or interpretation of data. KPB, GR, UST, JWC, RC, EPN, TB, AV: critical writing or revising the intellectual content. PAG: final approval of the version to be published.


This study was funded by a grant from Coramed Technologies, LLC and Haemonetics Corporation.

Compliance with ethical standards

Conflict of interest

Dr Gurbel reports serving as a consultant or receiving honoraria for lectures, consultations, including service on speakers’ bureaus from Bayer, Merck, Janssen, Medicure, and World Medical; receiving grants from the National Institutes of Health, Janssen, Bayer, Haemonetics, Instrumentation Labs, Coramed Technologies, LLC and Amgen. Dr. Gurbel is holding stock or stock options in Merck, Medtronic, and Pfizer; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Cochran serves on speakers bureau and does consulting for Merck, Avanir and Amgen. Dr. Raviv reports serving as a consultant for Haemonetics. Other authors report no disclosures.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethical committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11239_2019_1813_MOESM1_ESM.docx (398 kb)
Supplementary material 1 (DOCX 398 KB)


  1. 1.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics, Stroke Statistics Subcommitee (2017) Heart disease and stroke statistics-2017 update: a report from the american heart association. Circulation 135:e146–e603. CrossRefGoogle Scholar
  2. 2.
    Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H, American Heart Association Stroke, Council on Cardiovascular and Stroke Nursing, Council on Peripheral Vascular, Council on Clinical Cardiology (2013) Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870–947. CrossRefGoogle Scholar
  3. 3.
    Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke C (2018) 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49:e46–e110. CrossRefGoogle Scholar
  4. 4.
    Spanos K, Kouvelos G, Matsagkas M, Giannoukas AD (2017) Antiplatelet resistance in ischaemic stroke patients. Eur J Vasc Endovasc Surg 54:3–4. CrossRefGoogle Scholar
  5. 5.
    Oh MS, Yu KH, Lee JH, Jung S, Kim C, Jang MU, Lee J, Lee BC (2016) Aspirin resistance is associated with increased stroke severity and infarct volume. Neurology 86:1808–1817. CrossRefGoogle Scholar
  6. 6.
    Kim JT, Heo SH, Lee JS, Choi MJ, Choi KH, Nam TS, Lee SH, Park MS, Kim BC, Kim MK, Cho KH (2015) Aspirin resistance in the acute stages of acute ischemic stroke is associated with the development of new ischemic lesions. PLoS ONE 10:e0120743. CrossRefGoogle Scholar
  7. 7.
    Bliden KP, Chaudhary R, Mohammed N, Muresan AA, Lopez-Espina CG, Cohen E, Raviv G, Doubleday M, Zaman F, Mathew B, Tantry US, Gurbel PA (2017) Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6 s system. J Thromb Thrombolysis 43:437–445. CrossRefGoogle Scholar
  8. 8.
    Gurbel PA, Bliden KP, Tantry US, Monroe AL, Muresan AA, Brunner NE, Lopez-Espina CG, Delmenico PR, Cohen E, Raviv G, Haugen DL, Ereth MH (2016) First report of the point-of-care TEG: a technical validation study of the TEG-6S system. Platelets 27:642–649. CrossRefGoogle Scholar
  9. 9.
    Gurbel PA, Bliden KP, Navickas IA, Mahla E, Dichiara J, Suarez TA, Antonino MJ, Tantry US, Cohen E (2010) Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events. Am Heart J 160:346–354. CrossRefGoogle Scholar
  10. 10.
    Cocho D, Borrell M, Marti-Fabregas J, Montaner J, Castellanos M, Bravo Y, Molina-Porcel L, Belvis R, Diaz-Manera JA, Martinez-Domeno A, Martinez-Lage M, Millan M, Fontcuberta J, Marti-Vilalta JL (2006) Pretreatment hemostatic markers of symptomatic intracerebral hemorrhage in patients treated with tissue plasminogen activator. Stroke 37:996–999. CrossRefGoogle Scholar
  11. 11.
    Zakai NA, Olson NC, Judd SE, Kleindorfer DO, Kissela BM, Howard G, Cushman M (2017) Haemostasis biomarkers and risk of intracerebral haemorrhage in the reasons for geographic and racial differences in stroke study. Thromb Haemost 117:1808–1815. CrossRefGoogle Scholar
  12. 12.
    Maas MB, Furie KL (2009) Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med 3:363–383. CrossRefGoogle Scholar
  13. 13.
    Shen J, Li X, Li Y, Wu B (2017) Comparative accuracy of CT perfusion in diagnosing acute ischemic stroke: a systematic review of 27 trials. PLoS ONE 12:e0176622. CrossRefGoogle Scholar
  14. 14.
    Bustamante A, Lopez-Cancio E, Pich S, Penalba A, Giralt D, Garcia-Berrocoso T, Ferrer-Costa C, Gasull T, Hernandez-Perez M, Millan M, Rubiera M, Cardona P, Cano L, Quesada H, Terceno M, Silva Y, Castellanos M, Garces M, Reverte S, Ustrell X, Mares R, Baiges JJ, Serena J, Rubio F, Salas E, Davalos A, Montaner J (2017) Blood biomarkers for the early diagnosis of stroke: the stroke-chip study. Stroke 48:2419–2425. CrossRefGoogle Scholar
  15. 15.
    Sahlas DJ, Gould L, Swartz RH, Mohammed N, McNicoll-Whiteman R, Naufal F, Oczkowski W (2014) Tissue plasminogen activator overdose in acute ischemic stroke patients linked to poorer functional outcomes. J Stroke Cerebrovasc Dis 23:155–159. CrossRefGoogle Scholar
  16. 16.
    Nedelman CB, Glenn LL (2014) Effect of tissue plasminogen activator dose and interval on stroke severity. J Stroke Cerebrovasc Dis 23:197–198. CrossRefGoogle Scholar
  17. 17.
    Testa S, Legnani C, Tripodi A, Paoletti O, Pengo V, Abbate R, Bassi L, Carraro P, Cini M, Paniccia R, Poli D, Palareti G (2016) Poor comparability of coagulation screening test with specific measurement in patients receiving direct oral anticoagulants: results from a multicenter/multiplatform study. J Thromb Haemost 14:2194–2201. CrossRefGoogle Scholar
  18. 18.
    Tobin WO, Kinsella JA, Collins DR, Coughlan T, O’Neill D, Egan B, Tierney S, Feeley TM, Murphy RP, McCabe DJ (2011) Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study. Br J Haematol 152:640–647. CrossRefGoogle Scholar
  19. 19.
    McCabe DJ, Harrison P, Mackie IJ, Sidhu PS, Lawrie AS, Purdy G, Machin SJ, Brown MM (2005) Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA. Platelets 16:269–280. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kevin P. Bliden
    • 1
  • Gabe Raviv
    • 3
  • Udaya S. Tantry
    • 1
  • Rahul Chaudhary
    • 1
  • John W. Cochran
    • 2
  • Eliano P. Navarese
    • 1
  • Tricia Brannan
    • 2
  • Ankit Vyas
    • 1
  • Paul A. Gurbel
    • 1
    Email author
  1. 1.Inova Center for Thrombosis Research and Drug DevelopmentInova Heart and Vascular InstituteFalls ChurchUSA
  2. 2.Inova Neuroscience and Spine InstituteInova Fairfax HospitalFalls ChurchUSA
  3. 3.Coramed TechnologiesGlenviewUSA

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