{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:55:52Z","timestamp":1788184552159,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The contact system consists of coagulation factor XII (FXII), prekallikrein, and H-kininogen (HK) and plays important roles in many diseases. Plasma kallikrein (PKa) cleaved HK (cHK) is a marker of contact activation. Presently, we developed a specific and precise enzyme-linked immunosorbent assay (ELISA) for determination of cHK <jats:italic>in vitro<\/jats:italic> and <jats:italic>ex vivo.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cleaved HK specific mouse monoclonal antibodies (mAbs) were generated using a peptide corresponding to the PKa cleavage site on HK as immunogen. ELISA, surface plasmon resonance analysis, and immunoprecipitation established the specificity of the antibody, which subsequently was used in a sandwich ELISA. The analytical imprecision and the concentration of cHK in a reference population and in women receiving oral contraceptives (OC) were determined. cHK was assessed <jats:italic>in vitro<\/jats:italic> in plasma exposed to polytetrafluoroethylene, silicone, and glass tubes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The selected mAb showed excellent specificity towards cHK. The intra-assay and inter-assay CV of the ELISA were 3.6 and 6.0%, respectively. The reference population (60 women, 60 men) displayed a median cHK plasma concentration of 1.38 \u03bcg\/mL and a reference interval of 0.82 \u2013 2.56 \u03bcg\/mL. Women receiving OC had significantly higher concentrations, <jats:italic>p<\/jats:italic> &amp;lt; 0.001. cHK was significantly elevated in plasma exposed to polytetrafluoroethylene, <jats:italic>p<\/jats:italic> = 0.001, and glass, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ELISA showed excellent precision and specificity. cHK assessment <jats:italic>ex vivo<\/jats:italic> demonstrated ongoing contact activation in healthy individuals, augmented by OC. The cHK antibody and the ELISA could be promising tools in contact activation related diseases and <jats:italic>in vitro<\/jats:italic> investigations of the plasma compatibility of blood contacting biomaterials.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.873975","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T04:49:27Z","timestamp":1653022167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Plasma Kallikrein Cleaved H-kininogen: An End-Point Marker for Contact Activation in vitro and ex vivo"],"prefix":"10.3389","volume":"9","author":[{"given":"Yaseelan","family":"Palarasah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Thuy Duong","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen Brodersen","family":"Gram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas Heilskov","family":"Graversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Pilely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes Jakobsen","family":"Sidelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.3389\/fimmu.2019.02046","article-title":"Plasminflammation\u2014an emerging pathway to bradykinin production.","volume":"10","author":"Maas","year":"2019","journal-title":"Front Immunol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1055\/s-0036-1598003","article-title":"Factor XII contact activation.","volume":"43","author":"Naudin","year":"2017","journal-title":"Semin Thromb Hemost."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1182\/blood-2017-04-569111","article-title":"Coagulation factor XII in thrombosis and inflammation.","volume":"131","author":"Maas","year":"2018","journal-title":"Blood."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5144","DOI":"10.1016\/j.biomaterials.2007.07.035","article-title":"The catastrophe revisited: blood compatibility in the 21st century.","volume":"28","author":"Ratner","year":"2007","journal-title":"Biomaterials."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.actbio.2019.06.020","article-title":"The blood compatibility challenge. 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