{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:53:19Z","timestamp":1791643999782,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Administering intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) on direct oral anticoagulants (DOACs) remains a clinical challenge. Current guidelines restrict IVT within 48 h of DOAC intake unless anticoagulant activity can be confidently excluded. However, reliable medication histories are often unavailable, and conventional coagulation tests inadequately detect DOAC activity. This study evaluated whether viscoelastic point-of-care testing (ClotPro\u00ae) could identify the absence of anticoagulant effect in AIS patients on DOACs, thus enabling IVT administration and potentially improving clinical outcomes. Methods: We conducted a prospective observational cohort study of 40 AIS patients with documented DOAC use, admitted between February 2023 and May 2025. ClotPro\u00ae was performed at admission using the Russell\u2019s viper venom (RVV) assay for factor Xa inhibitors and the ecarin clotting time (ECT) assay for dabigatran. Subtherapeutic anticoagulation was defined as a clotting time (CT) of &lt;100 s for RVV and &lt;180 s for ECT, respectively. Patients identified as being subtherapeutic were assessed for IVT eligibility. To evaluate IVT effects, we performed propensity score-matched bootstrap resampling (1000 iterations), matching patients by age, admission National Institutes of Health Stroke Scale (NIHSS), and pre-stroke modified Rankin Scale (mRS). Primary endpoints were NIHSS-shift (change from admission to 72 h) and mRS-shift (change from pre-stroke mRS to 90-day mRS). Predictors of outcomes were analyzed using multivariate regression models. Results: ClotPro\u00ae identified 15\/40 patients (37.5%) as subtherapeutic, all on factor Xa inhibitors. Of these, seven received IVT. In matched analyses, IVT-treated patients showed a numerically greater neurological improvement than untreated patients (mean NIHSS-shift: \u22122.83 vs. 3.94; mean difference: \u22126.76, 95% confidence interval [CI]: \u221224.00 to 7.55; p = 0.495). Functional outcome by mRS-shift showed only minor differences between groups (2.74 vs. 2.10 mean difference: 0.64; 95% CI: \u22122.00 to 2.50; p = 0.510). IVT showed a favorable trend for early neurological recovery (p = 0.081) but was not independently associated with functional outcome (p = 0.380). Conclusions: ClotPro\u00ae identified a substantial subset of AIS patients on DOAC therapy without measurable anticoagulant activity, enabling IVT in cases that would otherwise have been excluded based on medication history. These findings support the feasibility of ClotPro\u00ae-guided decision-making in acute stroke care and highlight its potential to improve IVT selection by enabling real-time assessment of coagulation status at the bedside.<\/jats:p>","DOI":"10.3390\/neurolint17070103","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Viscoelastic Point-of-Care Testing (ClotPro\u00ae) to Guide Intravenous Thrombolysis in Acute Ischemic Stroke Patients on DOACs: Replacing History with Hemostasis in a Proof-of-Concept Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-0092","authenticated-orcid":false,"given":"Jessica","family":"Seetge","sequence":"first","affiliation":[{"name":"Stroke Unit, Department of Neurology, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Cs\u00e9ke","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia Nozomi","family":"Kar\u00e1di","sequence":"additional","affiliation":[{"name":"Stroke Unit, Department of Neurology, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edit","family":"Bosny\u00e1k","sequence":"additional","affiliation":[{"name":"Stroke Unit, Department of Neurology, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter Johanna","family":"Jozifek","sequence":"additional","affiliation":[{"name":"Stroke Unit, Department of Neurology, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Szap\u00e1ry","sequence":"additional","affiliation":[{"name":"Stroke Unit, Department of Neurology, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 13, P\u00e9cs, 7624 Baranya, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1161\/STR.0000000000000158","article-title":"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","volume":"49","author":"Powers","year":"2018","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Berge, E., Whiteley, W., Audebert, H., De Marchis, G., Fonseca, A.C., Padiglioni, C., P\u00e9rez de la Ossa, N., Strbian, D., Tsivgoulis, G., and Turc, G. (2021). European Stroke Organisation (ESO) Guidelines on Intravenous Thrombolysis for Acute Ischaemic Stroke. Eur. Stroke J., 6.","DOI":"10.1177\/2396987321989865"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wu, C., Qin, Y., Lin, Z., Yi, X., Wei, X., Ruan, Y., and He, J. (2020). Prevalence and Impact of Aphasia among Patients Admitted with Acute Ischemic Stroke. J. Stroke Cerebrovasc. Dis., 29.","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.104764"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dro\u015b, J., Kowalska, K., Pasi\u0144ska, P., and Klimkowicz-Mrowiec, A. (2023). Transient Cognitive Impairment in the Acute Phase of Stroke\u2014Prevalence, Risk Factors and Influence on Long-Term Prognosis in Population of Patients with Stroke (Research Study\u2014Part of the PROPOLIS Study). BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03120-x"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, J., Zhang, P., Wu, S., Yuan, R., Liu, J., Tao, W., Wang, D., and Liu, M. (2020). Impaired Consciousness at Stroke Onset in Large Hemisphere Infarction: Incidence, Risk Factors and Outcome. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-70172-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1136\/heartjnl-2016-310672","article-title":"Early Non-Persistence with Dabigatran and Rivaroxaban in Patients with Atrial Fibrillation","volume":"103","author":"Jackevicius","year":"2017","journal-title":"Heart"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/bcp.12366","article-title":"Coagulation Assays and Plasma Fibrinogen Concentrations in Real-world Patients with Atrial Fibrillation Treated with Dabigatran","volume":"78","author":"Chin","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1345\/aph.1R179","article-title":"Dabigatran Effects on the International Normalized Ratio, Activated Partial Thromboplastin Time, Thrombin Time, and Fibrinogen: A Multicenter, In Vitro Study","volume":"46","author":"Dager","year":"2012","journal-title":"Ann. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1160\/TH10-05-0328","article-title":"Clinical Laboratory Measurement of Direct Factor Xa Inhibitors: Anti-Xa Assay Is Preferable to Prothrombin Time Assay","volume":"104","author":"Barrett","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1309\/AJCPQ2NJD3PXFTUG","article-title":"Laboratory Measurements of the Oral Direct Factor Xa Inhibitor Edoxaban","volume":"143","author":"Morishima","year":"2015","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s00228-013-1550-4","article-title":"Evaluation of Coagulation Assays versus LC-MS\/MS for Determinations of Dabigatran Concentrations in Plasma","volume":"69","author":"Antovic","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1111\/jth.12308","article-title":"Performance of Coagulation Tests in Patients on Therapeutic Doses of Dabigatran: A Cross-sectional Pharmacodynamic Study Based on Peak and Trough Plasma Levels","volume":"11","author":"Hawes","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.thromres.2014.11.017","article-title":"Comparison of Methods to Determine Rivaroxaban Anti-Factor Xa Activity","volume":"135","author":"Rathbun","year":"2015","journal-title":"Thromb. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.thromres.2015.04.030","article-title":"Clinical Evaluation of Laboratory Methods to Monitor Apixaban Treatment in Patients with Atrial Fibrillation","volume":"136","author":"Skeppholm","year":"2015","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1016\/j.thromres.2011.07.026","article-title":"In Vitro Study of the Anticoagulant Effects of Edoxaban and Its Effect on Thrombin Generation in Comparison to Fondaparinux","volume":"129","author":"Samama","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000081506","article-title":"Ecarin Chromogenic Assay\u2014A New Method for Quantitative Determination of Direct Thrombin Inhibitors Like Hirudin","volume":"33","author":"Lange","year":"2003","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1097\/CCM.0b013e3182281af5","article-title":"Functional Definition and Characterization of Acute Traumatic Coagulopathy","volume":"39","author":"Davenport","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Navar, A.M., Kolkailah, A.A., Overton, R., Shah, N.P., Rousseau, J.F., Flaker, G.C., Pignone, M.P., and Peterson, E.D. (2022). Trends in Oral Anticoagulant Use Among 436\u2009864 Patients with Atrial Fibrillation in Community Practice, 2011 to 2020. J. Am. Heart Assoc., 11.","DOI":"10.1161\/JAHA.122.026723"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bhandari, M., Pradhan, A., Vishwakarma, P., Di Renzo, L., Iellamo, F., Ali, W., and Perrone, M.A. (2025). Direct Oral Anticoagulant Use in Older Adults with Atrial Fibrillation: Challenges and Solutions. Eur. Cardiol. Rev., 20.","DOI":"10.15420\/ecr.2024.17"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/ijlh.12744","article-title":"Impact of Four Direct Oral Anticoagulants on Rotational Thromboelastometry (ROTEM)","volume":"40","author":"Seyve","year":"2018","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/00365513.2017.1408138","article-title":"The Anticoagulant Effect of Therapeutic Levels of Dabigatran in Atrial Fibrillation Evaluated by Thrombelastography (TEG\u00ae), Hemoclot Thrombin Inhibitor (HTI) Assay and Ecarin Clotting Time (ECT)","volume":"78","author":"Solbeck","year":"2018","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"ref_22","unstructured":"Enicor GmbH ClotPro\u00ae (2025, June 19). The New Generation of Viscoelastic Testing. Available online: https:\/\/santair.gr\/wp-content\/uploads\/2021\/04\/flyer_enicor_EN_2020-04_with-.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Okada, T., Yoshimoto, T., Wada, S., Yoshimura, S., Chiba, T., Egashira, S., Kimura, S., Shiozawa, M., Inoue, M., and Ihara, M. (2022). Intravenous Thrombolysis with Alteplase at 0.6\u2009Mg\/Kg in Patients with Ischemic Stroke Taking Direct Oral Anticoagulants. J. Am. Heart Assoc., 11.","DOI":"10.1161\/JAHA.122.025809"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ghannam, M., AlMajali, M., Galecio-Castillo, M., Al Qudah, A., Khasiyev, F., Dibas, M., Ghazaleh, D., Vivanco-Suarez, J., Mor\u00e1n-Mari\u00f1os, C., and Farooqui, M. (2023). Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis. J. Am. Heart Assoc., 12.","DOI":"10.1161\/JAHA.123.031669"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1177\/23969873241252751","article-title":"Intravenous Thrombolysis in Patients with Recent Intake of Direct Oral Anticoagulants: A Target Trial Analysis after the Liberalization of Institutional Guidelines","volume":"9","author":"Jung","year":"2024","journal-title":"Eur. Stroke J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sahli, S.D., Castellucci, C., Roche, T.R., R\u00f6ssler, J., Spahn, D.R., and Kaserer, A. (2022). The Impact of Direct Oral Anticoagulants on Viscoelastic Testing\u2014A Systematic Review. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.991675"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12959-024-00659-8","article-title":"Monitoring the Efficiency of Reversal on Anti-Xa Direct Oral Anticoagulants Using Point-of-Care Viscoelastic Testing","volume":"22","author":"Heubner","year":"2024","journal-title":"Thromb. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1055\/a-1869-7853","article-title":"Point-of-Care Assessment of Direct Oral Anticoagulation in Acute Ischemic Stroke: Protocol for a Prospective Observational Diagnostic Accuracy Study","volume":"122","author":"Sedghi","year":"2022","journal-title":"Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Doeppner, T.R., Olbricht, L., Maxhuni, T., Alhaj Omar, O., Sachs, U.J., Juenemann, M.B., Huttner, H.B., and Gerner, S.T. (2023). Urine-Based Point-of-Care Testing for Factor-Xa-Inhibitors in Acute Ischemic Stroke Patients: A Feasibility Study. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1330421"}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/7\/103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:15Z","timestamp":1760032935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/7\/103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["neurolint17070103"],"URL":"https:\/\/doi.org\/10.3390\/neurolint17070103","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}