{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:27:33Z","timestamp":1786750053175,"version":"build-2736575974"},"reference-count":17,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Perosphere Technology, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:p>Currently, no sensitive, widely available, rapid turnaround assays to measure the effect on coagulation of direct oral anticoagulants exist.<\/jats:p>\n                  <jats:p>The point-of-care ClotChek (Perosphere Technologies Inc.) coagulometer was developed to address this unmet need with high sensitivity and precision. This proof-of-concept study aimed to determine normal clotting time in healthy, non-anticoagulated subjects; summarize clotting times at trough and peak drug concentrations in patients taking apixaban and rivaroxaban; and identify cut-points that maximize both sensitivity and specificity for predicting whether an individual is meaningfully anticoagulated.<\/jats:p>\n                  <jats:p>In 141 normal subjects, the mean clotting time was 244.2\u2009\u00b1\u200925.8\u2009seconds (median 244.0\u2009seconds; range 183\u2013296\u2009seconds). In 39 patients on apixaban, mean clotting times were 293.9\u2009\u00b1\u200932.5\u2009seconds at trough and 323.1\u2009\u00b1\u200927.9\u2009seconds at peak. In 42 patients on rivaroxaban, mean clotting times were 287.8\u2009\u00b1\u200944.9\u2009seconds at trough and 380.4\u2009\u00b1\u200941.2\u2009seconds at peak. Strong positive correlations are seen between the anticoagulant drug response determined by the assay and anticoagulant drug levels for apixaban (Spearman's rho\u2009=\u20090.74, p\u2009&lt;\u20090.0001) and for rivaroxaban (Spearman's rho\u2009=\u20090.82, p\u2009&lt;\u20090.0001). ClotChek clotting times showed good sensitivity and specificity to identify meaningful anticoagulation (&gt;75\u2009ng\/mL) among patients taking apixaban (AUC\u2009=\u20090.91, 83% sensitivity, 86% specificity) or rivaroxaban (AUC\u2009=\u20090.96, 91% sensitivity, 90% specificity). Similar results were seen using the lower threshold of &gt;30\u2009ng\/mL.<\/jats:p>\n                  <jats:p>These results require clinical validation in further studies but suggest that the ClotChek assay could aid physicians at the point of care in making therapeutic decisions in patients with adverse events associated with oral factor Xa inhibitors.<\/jats:p>","DOI":"10.1055\/a-2930-1041","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T22:50:57Z","timestamp":1785970257000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical Validation of a Point-of-Care Whole Blood Coagulometer in Patients on Factor Xa Inhibitors"],"prefix":"10.1055","clinical-trial-number":[{"clinical-trial-number":"nct04868214","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Sasha","family":"Bakhru","sequence":"additional","affiliation":[{"name":"Perosphere Technologies, Connecticut, United States","place":["Danbury"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Connors","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Massachusetts, United States","place":["Boston"],"department":["Hematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Massachusetts, United States","place":["Boston"]},{"name":"Brigham and Women's Hospital, Massachusetts, United States","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dardan","family":"Osmani","sequence":"additional","affiliation":[{"name":"Perosphere Technologies, Connecticut, United States","place":["Danbury"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Keenan","sequence":"additional","affiliation":[{"name":"Biomedical Statistical Consulting, LLC, Pennsylvania, United States","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Chen","sequence":"additional","affiliation":[{"name":"Perosphere Technologies, Connecticut, United States","place":["Danbury"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Perosphere Technologies, Connecticut, United States","place":["Danbury"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-9797","authenticated-orcid":false,"given":"Jack","family":"Ansell","sequence":"additional","affiliation":[{"name":"Hofstra Northwell Zucker School of Medicine, New Jersey, United States","place":["Long Branch"],"department":["Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/ijlh.14483","article-title":"Measuring direct oral anticoagulant (DOAC) levels: applications, limitations, and future directions","volume":"48","author":"S Mithoowani","year":"2026","journal-title":"Int J Lab Hematol"},{"issue":"19","key":"ref2","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1182\/blood-2018-04-791541","article-title":"Testing and monitoring direct oral anticoagulants","volume":"132","author":"J M Connors","year":"2018","journal-title":"Blood"},{"issue":"03","key":"ref3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1055\/s-0038-1676317","article-title":"A novel whole blood point-of-care coagulometer to measure the effect of direct oral anticoagulants and heparins","volume":"45","author":"J Ansell","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"7355","DOI":"10.1038\/s41598-025-92201-7","article-title":"Validation of a whole blood coagulometer sensitive to the direct oral anticoagulants","volume":"15","author":"S H Bakhru","year":"2025","journal-title":"Sci Rep"},{"issue":"08","key":"ref5","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/rth2.12418","article-title":"Andexanet versus prothrombin complex concentrates: differences in reversal of factor Xa inhibitors in in vitro thrombin generation","volume":"4","author":"G Lu","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"14","key":"ref6","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1056\/NEJMoa1814051","article-title":"Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors","volume":"380","author":"S J Connolly","year":"2019","journal-title":"N Engl J 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Limitations and solutions","volume":"48","author":"M Ebner","year":"2017","journal-title":"Stroke"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1111\/jth.13486","article-title":"Poor comparability of coagulation screening test with specific measurement in patients receiving direct oral anticoagulants: results from a multicenter\/multiplatform study","volume":"14","author":"S Testa","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref11","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1016\/j.jtha.2026.05.016","article-title":"A light in the dark-reframing direct oral anticoagulant pharmacokinetics and pharmacodynamics for near-patient decision-making","volume":"24","author":"J R Shaw","year":"2026","journal-title":"J Thromb Haemost"},{"issue":"18","key":"ref12","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1161\/CIRCULATIONAHA.118.033933","article-title":"Linking endogenous factor Xa activity, a biologically relevant pharmacodynamic marker, to edoxaban plasma concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 Trial","volume":"138","author":"O QP Yin","year":"2018","journal-title":"Circulation"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/jth.14001","article-title":"Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants","volume":"16","author":"S Testa","year":"2018","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref14","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/jth.14457","article-title":"Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants","volume":"17","author":"S Testa","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jacc.2013.07.104","article-title":"The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy)","volume":"63","author":"P A Reilly","year":"2014","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"ref16","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1111\/jth.15901","article-title":"Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure","volume":"20","author":"J R Shaw","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1055\/a-2521-0923","article-title":"Influence of direct oral anticoagulant levels and thrombin generation on postoperative bleeding [SONAR]: a nested case-control study","volume":"125","author":"J R Shaw","year":"2025","journal-title":"Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2930-1041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:11:18Z","timestamp":1786749078000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2930-1041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":17,"URL":"https:\/\/doi.org\/10.1055\/a-2930-1041","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8,5]]},"published":{"date-parts":[[2026,8,5]]}}}