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DOI: 10.1055/s-0041-1732341
Global Thrombosis Test: Occlusion by Coagulation or SIPA?
Funding The study is funded by Atlanta Center for Microsystems Engineered Point-of-Care Technologies, ACME-POCT with funding number of NIH-5U54EB027690.![](https://www.thieme-connect.de/media/10.1055-s-00033990/202103/lookinside/thumbnails/10-1055-s-0041-1732341_210025-1.jpg)
Abstract
The global thrombosis test (GTT) is a point of care device that tests thrombotic and thrombolytic status. The device exposes whole blood flow to a combination of both high and low shear stress past and between ball bearings potentially causing thrombin and fibrin formation. The question arises as to whether thrombosis in the GTT is dominated by coagulation-triggered red clot or high shear-induced white clot. We investigated the nature of the thrombus formed in the GTT, the device efficacy, human factors use, and limitations. The GTT formed clots that were histologically fibrin-rich with trapped red blood cells. The occlusion time (OT) was more consistent with coagulation than high shear white clot and was strongly lengthened by heparin and citrate, two common anticoagulants. The clot was lysed by tissue plasminogen activator (tPA), also consistent with a fibrin-rich red clot. Changing the bead to a collagen-coated surface and eliminating the low shear zone between the beads induced a rapid OT consistent with a platelet-rich thrombus that was relatively resistant to heparin or tPA. The evidence points to the GTT as occluding primarily due to fibrin-rich red clot from coagulation rather than high shear platelet aggregation and occlusion associated with arterial thrombosis.
* V.C. and P.J.Y. contributed equally as co-first authors.
Publikationsverlauf
Eingereicht: 18. Februar 2021
Angenommen: 16. Juni 2021
Artikel online veröffentlicht:
19. September 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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References
- 1 Principle & technical details—How GTT works. Accessed July 18, 2020 at: https://www.thromboquest.com/newpage
- 2 Home—Global Thrombosis Test. Accessed July 18, 2020 at: https://www.thromboquest.com/
- 3 Cadroy Y, Horbett TA, Hanson SR. Discrimination between platelet-mediated and coagulation-mediated mechanisms in a model of complex thrombus formation in vivo. J Lab Clin Med 1989; 113 (04) 436-448
- 4 Dittman WA, Majerus PW. Structure and function of thrombomodulin: a natural anticoagulant. Blood 1990; 75 (02) 329-336
- 5 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85 (06) 958-965
- 6 Jesty J, Nemerson Y. The pathways of blood coagulation. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ. eds. Williams Hematology. 5th ed.. McGraw-Hill; 1995: 1222-1238 https://accessmedicine.mhmedical.com/content.aspx?bookid=2962§ionid=253249871
- 7 Mann KG, Nesheim ME, Church WR, Haley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood 1990; 76 (01) 1-16
- 8 Casa LDC, Ku DN. Thrombus formation at high shear rates. Annu Rev Biomed Eng 2017; 19 (01) 415-433
- 9 Kim D, Bresette C, Liu Z, Ku DN. Occlusive thrombosis in arteries. APL Bioeng 2019; 3 (04) 041502
- 10 Jackson SP. The growing complexity of platelet aggregation. Blood 2007; 109 (12) 5087-5095
- 11 Bark Jr DL, Ku DN. Wall shear over high degree stenoses pertinent to atherothrombosis. J Biomech 2010; 43 (15) 2970-2977
- 12 Ku DN, Flannery CJ. Development of a flow-through system to create occluding thrombus. Biorheology 2007; 44 (04) 273-284
- 13 Carstairs KC. The identification of platelets and platelet antigens in histological sections. J Pathol Bacteriol 1965; 90 (01) 225-231
- 14 Yamamoto J, Inoue N, Otsui K, Ishii H, Gorog DA. Global Thrombosis Test (GTT) can detect major determinants of haemostasis including platelet reactivity, endogenous fibrinolytic and thrombin generating potential. Thromb Res 2014; 133 (05) 919-926
- 15 Tamura N, Kitajima I, Kawamura Y. et al. Important regulatory role of activated platelet-derived procoagulant activity in the propagation of thrombi formed under arterial blood flow conditions. Circ J 2009; 73 (03) 540-548
- 16 Saraf S, Christopoulos C, Salha IB, Stott DJ, Gorog DA. Impaired endogenous thrombolysis in acute coronary syndrome patients predicts cardiovascular death and nonfatal myocardial infarction. J Am Coll Cardiol 2010; 55 (19) 2107-2115
- 17 Spinthakis N, Farag M, Gue YX, Srinivasan M, Wellsted DM, Gorog DA. Effect of P2Y12 inhibitors on thrombus stability and endogenous fibrinolysis. Thromb Res 2019; 173: 102-108
- 18 Casa LDC, Deaton DH, Ku DN. Role of high shear rate in thrombosis. J Vasc Surg 2015; 61 (04) 1068-1080
- 19 Johar RS, Smith RP. Assessing gravimetric estimation of intraoperative blood loss. J Gynecol Surg 1993; 9 (03) 151-154
- 20 Mehrabadi M, Casa LDC, Aidun CK, Ku DN. A predictive model of high shear thrombus growth. Ann Biomed Eng 2016; 44 (08) 2339-2350
- 21 Movat HZ. Demonstration of all connective tissue elements in a single section; pentachrome stains. AMA Arch Pathol 1955; 60 (03) 289-295
- 22 Roman N, Perkins SF, Perkins Jr EM, Dolnick EH. Orcein-hematoxylin in iodized ferric chloride as a stain for elastic fibers, with metanil yellow counterstaining. Stain Technol 1967; 42 (04) 199-202
- 23 Para A, Bark D, Lin A, Ku D. Rapid platelet accumulation leading to thrombotic occlusion. Ann Biomed Eng 2011; 39 (07) 1961-1971
- 24 Para AN, Ku DN. A low-volume, single pass in-vitro system of high shear thrombosis in a stenosis. Thromb Res 2013; 131 (05) 418-424
- 25 Kim DA, Ashworth KJ, Di Paola J, Ku DN. Platelet α-granules are required for occlusive high-shear-rate thrombosis. Blood Adv 2020; 4 (14) 3258-3267
- 26 Neeves KB, Onasoga AA, Hansen RR. et al. Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays. PLoS One 2013; 8 (01) e54680
- 27 Griffin MT, Kim D, Ku DN. Shear-induced platelet aggregation: 3D-grayscale microfluidics for repeatable and localized occlusive thrombosis. Biomicrofluidics 2019; 13 (05) 054106
- 28 Gorog D, Becker R. Point-of-care platelet function tests: relevance to arterial thrombosis and opportunities for improvement. J Thromb Thrombolysis 2021; 51: 1-11
- 29 Siedlecki CA. ed. Hemocompatibility of Biomaterials for Clinical Applications. Elsevier; 2018. https://doi.org/10.1016/C2014-0-04140-8 (https://www.elsevier.com/books/hemocompatibility-of-biomaterials-for-clinical-applications/siedlecki/978-0-08-100497-5)
- 30 Taomoto K, Ohnishi H, Kuga Y. et al. Platelet function and spontaneous thrombolytic activity of patients with cerebral infarction assessed by the global thrombosis test. Pathophysiol Haemost Thromb 2010; –10 37 (01) 43-48
- 31 Suehiro A, Wakabayashi I, Uchida K, Yamashita T, Yamamoto J. Impaired spontaneous thrombolytic activity measured by global thrombosis test in males with metabolic syndrome. Thromb Res 2012; 129 (04) 499-501
- 32 Suehiro A, Wakabayashi I, Yamashita T, Yamamoto J. Attenuation of spontaneous thrombolytic activity measured by the global thrombosis test in male habitual smokers. J Thromb Thrombolysis 2014; 37 (04) 414-418
- 33 Otsui K, Gorog DA, Yamamoto J. et al. Global Thrombosis Test—a possible monitoring system for the effects and safety of dabigatran. Thromb J 2015; 13 (01) 39
- 34 Rosser G, Tricoci P, Morrow D. et al. PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease. J Thromb Thrombolysis 2014; 38 (04) 423-429
- 35 Yamamoto J, Yamashita T, Ikarugi H. et al. Görög Thrombosis Test: a global in-vitro test of platelet function and thrombolysis. Blood Coagul Fibrinolysis 2003; 14 (01) 31-39
- 36 Ikarugi H, Yamashita T, Aoki R, Ishii H, Kanki K, Yamamoto J. Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test. Blood Coagul Fibrinolysis 2003; 14 (08) 781-784
- 37 Nishida H, Murata M, Miyaki K, Omae K, Watanabe K, Ikeda Y. Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation. Blood Coagul Fibrinolysis 2006; 17 (03) 203-207
- 38 Saraf S, Wellsted D, Sharma S, Gorog DA. Shear-induced global thrombosis test of native blood: pivotal role of ADP allows monitoring of P2Y12 antagonist therapy. Thromb Res 2009; 124 (04) 447-451