{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:47:06Z","timestamp":1787237226620,"version":"build-2736575974"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000801","name":"Bayer HealthCare","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000801","id-type":"DOI","asserted-by":"crossref"}]},{"name":"van de Laar Stichting"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>Background\u2003Hemophilia A (HA) is characterized by decreased or absent factor VIII (FVIII) activity. Current FVIII assays are based on clotting time and thus only provide information about the initiation of coagulation. In contrast, thrombin generation assays (TGAs) can be used to measure the full coagulation spectrum of initiation, propagation, and termination that provide information on the whole course of thrombin generation and inhibition. However, the commercially available TG kits lack sensitivity for measurements of hemophilia plasma within lower FVIII ranges, which is essential for explaining differences in bleeding phenotypes in hemophiliacs at clinically low levels of FVIII.<\/jats:p>\n                  <jats:p>Aims\u2003Optimization of the TGA for measurements of low FVIII levels in severe HA patients.<\/jats:p>\n                  <jats:p>Methods\u2003TGA measurements were performed in severe HA pooled plasma (n\u2009=\u200910). Investigations of several preanalytical and analytical variables of the assay were performed in a stepwise process and adjusted based on sensitivity toward intrinsic coagulation activation.<\/jats:p>\n                  <jats:p>Results\u2003TGA initiated by tissue factor (TF) alone at varying concentrations was unable to significantly differentiate between FVIII levels below 20%. In contrast, TGA activation with low concentrations of TF in presence of FXIa appeared to be highly sensitive for FVIII changes both in high and low ranges. In addition, a representative TGA curve at trough levels could only be produced using the dual TF\/FXIa TGA.<\/jats:p>\n                  <jats:p>Conclusion\u2003We propose a critical optimization for the setup of the TGA for measurements in severe HA plasma. The dual TF\/FXIa TGA shows increased sensitivity, especially in lower FVIII ranges, which allows for better individual characterization at baseline, prediction of interventions, and follow-up.<\/jats:p>","DOI":"10.1055\/a-2101-7961","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T19:03:44Z","timestamp":1685127824000},"page":"1034-1041","source":"Crossref","is-referenced-by-count":7,"title":["Sensitive Measurement of Clinically Relevant Factor VIII Levels in Thrombin Generation Assays Requires Presence of Factor XIa"],"prefix":"10.1055","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-7590","authenticated-orcid":false,"given":"Tom W.","family":"van de Berg","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands"},{"name":"Department of Hematology, Division of Internal Medicine, Maastricht UMC\u2009+\u2009, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A. M.","family":"Beckers","sequence":"additional","affiliation":[{"name":"Department of Hematology, Division of Internal Medicine, Maastricht UMC\u2009+\u2009, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor C. J. I.","family":"Heubel-Moenen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Division of Internal Medicine, Maastricht UMC\u2009+\u2009, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M. C.","family":"Henskens","sequence":"additional","affiliation":[{"name":"Central Diagnostics Laboratory, Maastricht UMC\u2009+\u2009, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Christella L. G. D.","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman M.","family":"Hackeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/jth.12672","article-title":"Definitions in hemophilia: communication from the SSC of the ISTH","volume":"12","author":"V S Blanchette","year":"2014","journal-title":"J Thromb 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