BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (<6 hours) with or without intravenous thrombolysis. Interventional procedure parameters, hemocoagulation markers, vWF, ADAMTS13, and histological examination of the extracted thrombi were performed. The National Institutes of Health Stroke Scale (NIHSS) score was used on hospital admission, after 24 hours, at day 7; the three-month modified Rankin Scale score was used. RESULTS Mechanical thrombectomy resulted in a Treatment in Cerebral Ischemia (TICI) score of 2-3, with recanalization in 89% of patients. Intravenous thrombolysis was used in 101 (78%). Patients with and without intravenous thrombolysis therapy had a good clinical outcome (score 0-2) in 47% of cases (P=0.459) using the three-month modified Rankin Scale. Patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥15 had significantly increased vWF levels (P=0.003), and a significantly increased vWF: ADAMTS13 ratio (P=0.038) on hospital admission. Significant correlation coefficients were found for plasma vWF and thrombo-embolus vWF (r=0.32), platelet (r=0.24), and fibrin (r=0.26) levels. In the removed thrombus, vWF levels were significantly correlated with platelet count (r=0.53), CD31-positive cells (r=0.38), and fibrin (r=0.48). CONCLUSIONS In patients with acute ischemic stroke, mechanical cerebral artery thrombectomy resulted in a good clinical outcome in 47% of cases, with and without intravenous thrombolysis therapy.

Blood Centre University Hospital Ostrava Ostrava Czech Republic

Department of Anesthesiology Resuscitation and Intensive Medicine Clinic University Hospital Ostrava Ostrava Czech Republic

Department of Applied Mathematics VŠB Technical University of Ostrava Ostrava Czech Republic

Department of Cell and Developmental Biology University of Pensylvania School of Medicine Philadelphia PA USA

Department of Clinical Hematology University Hospital Ostrava Ostrava Czech Republic

Department of Deputy Director of Science and Research University Hospital Ostrava Ostrava Czech Republic

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Department of Neurology University Hospital Ostrava Ostrava Czech Republic

Department of Pathology University Hospital Ostrava Ostrava Czech Republic

Department of Radiology University Hospital Ostrava Ostrava Czech Republic

SPADIA LAB Plc Ostrava Czech Republic

Zobrazit více v PubMed

Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20. PubMed

Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–30. PubMed

Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285–95. PubMed

Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009–18. PubMed

Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372:2296–306. PubMed

Heshmatollah A, Fransen PSS, Berkhemer OA, et al. Endovascular thrombectomy in patients with acute ischemic stroke and atrial fibrillation. A MR CLEAN subgroup analysis. EuroIntervention. 2017;13:996–1002. PubMed

Saver JL, Goyal M, Bonafe A, et al. Solitaire with the intention for thrombectomy as primary endovascular treatment for acute ischemic stroke (SWIFT PRIME) trial: Protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke. Int J Stroke. 2015;10:439–48. PubMed PMC

Kidwell CS, Jahan R, Alger JR, et al. Design and rationale of the mechanical retrieval and recanalization of stroke clots using embolectomy (MR RESCUE) Trial. Int J Stroke. 2014;9:110–16. PubMed PMC

Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: A meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387:1723–31. PubMed

Zaidi SF, Aghaebrahim A, Urra X, et al. Final infarct volume is a stronger predictor of outcome than recanalization in patients with proximal middle cerebral artery occlusion treated with endovascular therapy. Stroke. 2012;43:3238–44. PubMed

MacIsaac RL, Khatri P, Bendszus M, et al. A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: Statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration. Int J Stroke. 2015;10(Suppl A100):136–44. PubMed

Fargen KM, Neal D, Fiorella DJ, et al. A meta-analysis of prospective randomized controlled trials evaluating endovascular therapies for acute ischemic stroke. J Neurointerv Surg. 2015;7:84–89. PubMed

Elgendy IY, Kumbhani DJ, Mahmoud A, et al. Mechanical thrombectomy for acute ischemic stroke: A meta-analysis of randomized trials. J Am Coll Cardiol. 2015;66:2498–505. PubMed

Hernandez-Fernandez F, Rojas-Bartolome L, Garcia-Garcia J, et al. Histopathological and bacteriological analysis of thrombus material extracted during mechanical thrombectomy in acute stroke patients. Cardiovasc Intervent Radiol. 2017;40:1851–60. PubMed

Schuhmann MK, Gunreben I, Kleinschnitz C, Kraft P. Immunohistochemical analysis of cerebral thrombi retrieved by mechanical thrombectomy from patients with acute ischemic stroke. Int J Mol Sci. 2016;17:298. PubMed PMC

Iadecola C, Anrather J. The immunology of stroke: From mechanisms to translation. Nat Med. 2011;17:796–808. PubMed PMC

Wysokinski WE, Owen WG, Fass DN, et al. Atrial fibrillation and thrombosis: Immunohistochemical differences between in situ and embolized thrombi. J Thromb Haemost. 2004;2:1637–44. PubMed

Watson T, Arya A, Sulke N, Lip GY. Relationship of indices of inflammation and thrombogenesis to arrhythmia burden in paroxysmal atrial fibrillation. Chest. 2010;137:869–76. PubMed

Denorme F, Langhauser F, Desender L, et al. ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice. Blood. 2016;127:2337–45. PubMed

Kawecki C, Lenting PJ, Denis CV. von Willebrand factor and inflammation. J Thromb Haemost. 2017;15:1285–94. PubMed

Ruggeri ZM. The role of von Willebrand factor in thrombus formation. Thromb Res. 2007;120(Suppl 1):S5–9. PubMed PMC

Bongers TN, de Maat MP, van Goor ML, et al. High von Willebrand factor levels increase the risk of first ischemic stroke: Influence of ADAMTS13, inflammation, and genetic variability. Stroke. 2006;37:2672–77. PubMed

Khan MM, Motto DG, Lentz SR, Chauhan AK. ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice. J Thromb Haemost. 2012;10:1665–71. PubMed PMC

Ammash N, Konik EA, McBane RD, et al. Left atrial blood stasis and Von Willebrand factor-ADAMTS13 homeostasis in atrial fibrillation. Arterioscler Thromb Vasc Biol. 2011;31:2760–66. PubMed

Dong JF. Cleavage of ultra-large von Willebrand factor by ADAMTS13 under flow conditions. J Thromb Haemost. 2005;3:1710–16. PubMed

Xu H, Cao Y, Yang X, et al. ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery. Blood. 2017;130:11–22. PubMed PMC

De Meyer SF, Stoll G, Wagner DD, Kleinschnitz C. von Willebrand factor: An emerging target in stroke therapy. Stroke. 2012;43:599–606. PubMed PMC

Luo GP, Ni B, Yang X, Wu YZ. von Willebrand factor: More than a regulator of hemostasis and thrombosis. Acta Haematol. 2012;128:158–69. PubMed

Gragnano F, Sperlongano S, Golia E, et al. The role of von Willebrand factor in vascular inflammation: From pathogenesis to targeted therapy. Mediators Inflamm. 2017;2017:5620314. PubMed PMC

Striz I, Trebichavsky I. Calprotectin – a pleiotropic molecule in acute and chronic inflammation. Physiol Res. 2004;53:245–53. PubMed

De Meyer SF, Andersson T, Baxter B, et al. Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions. Int J Stroke. 2017;12:606–14. PubMed

Simons N, Mitchell P, Dowling R, et al. Thrombus composition in acute ischemic stroke: A histopathological study of thrombus extracted by endovascular retrieval. J Neuroradiol. 2015;42:86–92. PubMed

Sousa NC, Anicchino-Bizzacchi JM, Locatelli MF, et al. The relationship between ABO groups and subgroups, factor VIII and von Willebrand factor. Haematologica. 2007;92:236–39. PubMed

Conway DS, Pearce LA, Chin BS, et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation. 2003;107:3141–45. PubMed

Fukuchi M, Watanabe J, Kumagai K, et al. Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage. J Am Coll Cardiol. 2001;37:1436–42. PubMed

Hyseni A, Kemperman H, de Lange DW, et al. Active von Willebrand factor predicts 28-day mortality in patients with systemic inflammatory response syndrome. Blood. 2014;123:2153–56. PubMed

Groot E, de Groot PG, Fijnheer R, Lenting PJ. The presence of active von Willebrand factor under various pathological conditions. Curr Opin Hematol. 2007;14:284–89. PubMed

Tita-Nwa F, Bos A, Adjei A, et al. Correlates of D-dimer in older persons. Aging Clin Exp Res. 2010;22:20–23. PubMed PMC

Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J. 2007;37:607–13. PubMed

Christersson C, Wallentin L, Andersson U, et al. D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation – observations from the ARISTOTLE trial. J Thromb Haemost. 2014;12:1401–12. PubMed

Habara S, Dote K, Kato M, et al. Prediction of left atrial appendage thrombi in non-valvular atrial fibrillation. Eur Heart J. 2007;28:2217–22. PubMed

Mahe I, Drouet L, Chassany O, et al. A characteristic of the coagulation state of each patient with chronic atrial fibrillation. Thromb Res. 2002;107:1–6. PubMed

Brill A, Fuchs TA, Chauhan AK, et al. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011;117:1400–7. PubMed PMC

Almekhlafi MA, Hu WY, Hill MD, Auer RN. Calcification and endothelialization of thrombi in acute stroke. Ann Neurol. 2008;64:344–48. PubMed

Liebeskind DS, Sanossian N, Yong WH, et al. CT and MRI early vessel signs reflect clot composition in acute stroke. Stroke. 2011;42:1237–43. PubMed PMC

Marder VJ, Chute DJ, Starkman S, et al. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke. 2006;37:2086–93. PubMed

Niesten JM, van der Schaaf IC, van Dam L, et al. Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation. PLoS One. 2014;9:e88882. PubMed PMC

Gosk-Bierska I, McBane RD, Wu Y, et al. Platelet factor XIII gene expression and embolic propensity in atrial fibrillation. Thromb Haemost. 2011;106:75–82. PubMed

von Bruhl ML, Stark K, Steinhart A, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209:819–35. PubMed PMC

Downing LJ, Strieter RM, Kadell AM, et al. Neutrophils are the initial cell type identified in deep venous thrombosis induced vein wall inflammation. ASAIO J. 1996;42:M677–82. PubMed

Longstaff C, Varju I, Sotonyi P, et al. Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones. J Biol Chem. 2013;288:6946–56. PubMed PMC

Oklu R, Albadawi H, Watkins MT, et al. Detection of extracellular genomic DNA scaffold in human thrombus: Implications for the use of deoxyribonuclease enzymes in thrombolysis. J Vasc Interv Radiol. 2012;23:712–18. PubMed

Laridan O, Denorme F, Desender L, et al. Neutrophil extracellular traps in ischemic stroke thrombi. Ann Neurol. 2017;82:223–32. PubMed

Comparison of Mechanical Thrombectomy with Contact Aspiration, Stent Retriever, and Combined Procedures in Patients with Large-Vessel Occlusion in Acute Ischemic Stroke