Background and Purpose: The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. Methods: We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. Results: One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (p < 0.001), low percentage of red blood cells (p < 0.001), and lower rHU (p < 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (p ≤ 0.001) and low percentage of red blood cells (p ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (p ≤ 0.001), whereas thrombi with high amounts of erythrocytes correlated with shorter intervention times (p ≤ 0.001). ROC analysis revealed reliable prediction of secondary embolisms for low rHU (AUC = 0.746; p ≤ 0.0001), low amounts of RBC (AUC = 0.764; p ≤ 0.0001), and high amounts of fibrin (AUC = 0.773; p ≤ 0.0001). Conclusions: Fibrin-rich thrombi with low erythrocyte percentage are significantly associated with longer intervention times. Embolisms in the thrombectomy process occur more often in thrombi with a small fraction of red blood cells and a low CT-density, suggesting a higher fragility of these thrombi.

Sporns PB, Hanning U, Schmidt R, Schwindt W, Heindel W, Zoubi T, et al: Ischemic Stroke: what does the histological composition tell us about the origin of the thrombus? Stroke 2017; 48: 2206–2210.
Liebeskind DS, Sanossian N, Yong WH, Starkman S, Tsang MP, Moya AL, et al: CT and MRI early vessel signs reflect clot composition in acute stroke. Stroke 2011; 42: 1237–1243.
Marder VJ, Chute DJ, Starkman S, Abolian AM, Kidwell C, Liebeskind D, et al: Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 2006; 37: 2086–2093.
Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, et al: Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation 1989; 79: 920–928.
Kirchhof K, Sikinger M, Welzel T, Zoubaa S, Sartor K: [Does the result of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in rabbits depend on the erythrocyte- and fibrin-content of a thrombus?] Rofo 2004; 176: 98–105.
Boeckh-Behrens T, Schubert M, Forschler A, Prothmann S, Kreiser K, Zimmer C, et al: The impact of histological clot composition in embolic stroke. Clin Neuroradiol 2016; 26: 189–197.
Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, et al: Thrombus histology suggests cardioembolic cause in cryptogenic stroke. Stroke 2016; 47: 1864–1871.
Almekhlafi MA, Hu WY, Hill MD, Auer RN: Calcification and endothelialization of thrombi in acute stroke. Ann Neurol 2008; 64: 344–348.
Simons N, Mitchell P, Dowling R, Gonzales M, Yan B: Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval. J Neuroradiol 2015; 42: 86–92.
Brekenfeld C, Gralla J, Zubler C, Schroth G: Mechanical thrombectomy for acute ischemic stroke. Rofo 2012; 184: 503–512.
Roth C, Papanagiotou P, Behnke S, Walter S, Haass A, Becker C, et al: Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions. Stroke 2010; 41: 2559–2567.
Hashimoto T, Hayakawa M, Funatsu N, Yamagami H, Satow T, Takahashi JC, et al: Histopathologic analysis of retrieved thrombi associated with successful reperfusion after acute stroke thrombectomy. Stroke 2016; 47: 3035–3037.
De Meyer SF, Andersson T, Baxter B, Bendszus M, Brouwer P, Brinjikji W, et al: Analyses of thrombi in acute ischemic stroke: a consensus statement on current knowledge and future directions. Int J Stroke 2017; 12: 606–614.
Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, et al: Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 2003; 34:e109–e137.
Velasco A, Buerke B, Stracke CP, Berkemeyer S, Mosimann PJ, Schwindt W, et al: Comparison of a balloon guide catheter and a non-balloon guide catheter for mechanical thrombectomy. Radiology 2016; 280: 169–176.
Wohner N: Role of cellular elements in thrombus formation and dissolution. Cardiovasc Hematol Agents Med Chem 2008; 6: 224–228.
Moftakhar P, English JD, Cooke DL, Kim WT, Stout C, Smith WS, et al: Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke. Stroke 2013; 44: 243–245.
Mokin M, Morr S, Natarajan SK, Lin N, Snyder KV, Hopkins LN, et al: Thrombus density predicts successful recanalization with Solitaire stent retriever thrombectomy in acute ischemic stroke. J Neurointerv Surg 2015; 7: 104–107.
Froehler MT, Tateshima S, Duckwiler G, Jahan R, Gonzalez N, Vinuela F, et al: The hyperdense vessel sign on CT predicts successful recanalization with the merci device in acute ischemic stroke. J Neurointerv Surg 2013; 5: 289–293.
Niesten JM, van der Schaaf IC, van Dam L, Vink A, Vos JA, Schonewille WJ, et al: Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation. PLoS One 2014; 9:e88882.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.