BACKGROUND AND PURPOSE: The ANNEXA-4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. METHODS: Thirty patients were randomly selected from the ANNEXA-4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty-eight different ANNEXA-4 subjects were also randomly selected to assess intra-rater reliability of total ICrH volume measurement change at baseline and 12-h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA-4. RESULTS: Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. CONCLUSION: Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Biopharmaceuticals R and D AstraZeneca Mölndal Sweden

Czech National Centre for Evidence Based Healthcare and Knowledge Translation Faculty of Medicine Masaryk University Brno Czech Republic

Department of Clinical Neurosciences University of Calgary Calgary Canada

Department of Medicine Division of Neurology Royal Columbian Hospital New Westminster Canada

Department of Medicine Division of Neurology University of Alberta Edmonton Canada

Department of Medicine McMaster University Hamilton Ontario Canada

Department of Neurology Kyoto Prefectural University of Medicine Kyoto Japan

Department of Neurology University Hospital Ostrava Ostrava Czech Republic

Department of Radiology Seoul Medical Center Seoul South Korea

Department of Radiology University of Calgary Calgary Canada

Faculty of Medicine Masaryk University Brno Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Unit of Neurology San Jacopo Hospital Pistoia Italy

University Hospital Carl Gustav Carus Dresden Dresden Germany

Zobrazit více v PubMed

Brouwers, H. B. , Chang, Y. , Falcone, G. J. , Cai, X. , Ayres, A. M. , Battey, T. W. K. , Vashkevich, A. , Mcnamara, K. A. , Valant, V. , Schwab, K. , Orzell, S. C. , Bresette, L. M. , Feske, S. K. , Rost, N. S. , Romero, J. M. , Viswanathan, A. , Chou, S. H.‐Y. , Greenberg, S. M. , Rosand, J. , & Goldstein, J. N. (2014). Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurology, 71, 158–164. PubMed PMC

Christensen, M. C. , Mayer, S. , & Ferran, J.‐M. (2009). Quality of life after intracerebral hemorrhage: Results of the factor seven for acute hemorrhagic stroke (fast) trial. Stroke; A Journal of Cerebral Circulation, 40, 1677–1682. PubMed

Connolly, S. J. , Milling, T. J. , Eikelboom, J. W. , Gibson, C. M. , Curnutte, J. T. , Gold, A. , Bronson, M. D. , Lu, G. , Conley, P. B. , Verhamme, P. , Schmidt, J. , Middeldorp, S. , Cohen, A. T. , Beyer‐Westendorf, J. , Albaladejo, P. , Lopez‐Sendon, J. , Goodman, S. , Leeds, J. , Wiens, B. L. , … Crowther, M. (2016). Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. New England Journal of Medicine, 375, 1131–1141. PubMed PMC

Davis, S. M. , Broderick, J. , Hennerici, M. , Brun, N. C. , Diringer, M. N. , Mayer, S. A. , Begtrup, K. , & Steiner, T. (2006). Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology, 66, 1175–1181. PubMed

Demchuk, A. M. , Dowlatshahi, D. , Rodriguez‐Luna, D. , Molina, C. A. , Blas, Y. S. , Dzialowski, I. , Kobayashi, A. , Boulanger, J.‐M. , Lum, C. , Gubitz, G. , Padma, V. , Roy, J. , Kase, C. S. , Kosior, J. , Bhatia, R. , Tymchuk, S. , Subramaniam, S. , Gladstone, D. J. , Hill, M. D. , & Aviv, R. I. (2012). Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT‐angiography spot sign (predict): A prospective observational study. Lancet Neurology, 11, 307–314. PubMed

Dontje, M. L. , Dall, P. M. , Skelton, D. A. , Gill, J. M. R. , & Chastin, S. F. M. (2018). Reliability, minimal detectable change and responsiveness to change: Indicators to select the best method to measure sedentary behaviour in older adults in different study designs. PLoS ONE, 13, e0195424. PubMed PMC

Fogelholm, R. (2005). Long term survival after primary intracerebral haemorrhage: A retrospective population based study. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 1534–1538. PubMed PMC

Gavrielides, M. A. , Li, Q. , Zeng, R. , Myers, K. J. , Sahiner, B. , & Petrick, N. (2013). Minimum detectable change in lung nodule volume in a phantom CT study. Academic Radiology, 20, 1364–1370. PubMed

Hemphill, J. C. , Bonovich, D. C. , Besmertis, L. , Manley, G. T. , & Johnston, S. C. (2001). The ICH score: A simple, reliable grading scale for intracerebral hemorrhage. Stroke; A Journal of Cerebral Circulation, 32, 891–897. PubMed

Katajapuu, N. , Heinonen, A. , & Saltychev, M. (2020). Minimal clinically important difference and minimal detectable change of the world health organization disability assessment schedule 2.0 (whodas 2.0) amongst patients with chronic musculoskeletal pain. Clinical Rehabilitation, 34, 1506–1511. PubMed PMC

Kosior, J. C. , Idris, S. , Dowlatshahi, D. , Alzawahmah, M. , Eesa, M. , Sharma, P. , Tymchuk, S. , Hill, M. D. , Aviv, R. I. , Frayne, R. , Demchuk, A. M. , & PREDICT/Sunnybrook CTA ICH Study Investigators . (2011). Quantomo: Validation of a computer‐assisted methodology for the volumetric analysis of intracerebral haemorrhage. International Journal of Stroke, 6, 302–305. PubMed

Oda, S. , Awai, K. , Murao, K. , Ozawa, A. , Yanaga, Y. , Kawanaka, K. , & Yamashita, Y. (2010). Computer‐aided volumetry of pulmonary nodules exhibiting ground‐glass opacity at MDCT. AJR, American Journal of Roentgenology, 194, 398–406. PubMed

Oxnard, G. R. , Zhao, B. , Sima, C. S. , Ginsberg, M. S. , James, L. P. , Lefkowitz, R. A. , Guo, P. , Kris, M. G. , Schwartz, L. H. , & Riely, G. J. (2011). Variability of lung tumor measurements on repeat computed tomography scans taken within 15 minutes. Journal of Clinical Oncology, 29, 3114–3119. PubMed PMC

Piedrahita‐Alonso, E. , Valverde‐Megias, A. , Martin‐Garcia, B. , Hernandez‐Garcia, E. , & Gomez‐de‐Liano, R. (2021). Minimal detectable change of the disc‐fovea angle for ocular torsion assessment. Ophthalmic & Physiological Optics, 42(1), 133–139. PubMed

Rodriguez‐Luna, D. , Boyko, M. , Subramaniam, S. , Klourfeld, E. , Jo, P. , Diederichs, B. J. , Kosior, J. C. , Dowlatshahi, D. , Aviv, R. I. , Molina, C. A. , Hill, M. D. , & Demchuk, A. M. (2016). Magnitude of hematoma volume measurement error in intracerebral hemorrhage. Stroke; A Journal of Cerebral Circulation, 47, 1124–1126. PubMed

Rost, N. S. , Smith, E. E. , Chang, Y. , Snider, R. W. , Chanderraj, R. , Schwab, K. , Fitzmaurice, E. , Wendell, L. , Goldstein, J. N. , Greenberg, S. M. , & Rosand, J. (2008). Prediction of functional outcome in patients with primary intracerebral hemorrhage: The FUNC score. Stroke; A Journal of Cerebral Circulation, 39, 2304–2309. PubMed

Sacco, S. , Marini, C. , Toni, D. , Olivieri, L. , & Carolei, A. (2009). Incidence and 10‐year survival of intracerebral hemorrhage in a population‐based registry. Stroke; A Journal of Cerebral Circulation, 40, 394–399. PubMed

Zahuranec, D. B. , Lisabeth, L. D. , Sánchez, B. N. , Smith, M. A. , Brown, D. L. , Garcia, N. M. , Skolarus, L. E. , Meurer, W. J. , Burke, J. F. , Adelman, E. E. , & Morgenstern, L. B. (2014). Intracerebral hemorrhage mortality is not changing despite declining incidence. Neurology, 82, 2180–2186. PubMed PMC

Initial intraventricular involvement and early intracerebral hematoma retraction: The "ventricular washout"