{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:02:14Z","timestamp":1747184534685,"version":"3.40.5"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Absolute or relative protein (P)C pathway abnormalities (PC deficiency, PS deficiency, antiphospholipid syndrome (APS), factor (F)V\u2010abnormality, and high FVIII level) cause thrombophilia. Although screening assays for these thrombophilias are available, one utilizing clot waveform analysis (CWA) remains unknown. We aimed to establish a CWA\u2010based screening assay to distinguish PC pathway abnormality\u2010related thrombophilia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Samples were reacted with tissue factor (TF)\/phospholipids and recombinant thrombomodulin (rTM; optimal 20\u2009nM), followed by CWA measurement. The peak ratio (with\/without rTM) of the first derivative curve of clot waveform was calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The peak ratio in healthy plasmas (<jats:italic>n<\/jats:italic>\u00a0=\u00a035) was 0.36\u2009\u00b1\u20090.13; hence, the cutoff value was set to 0.49. The peak ratios in plasmas with PC deficiency, PS deficiency, high\u2010FVIII (spiked 300\u2009IU\/dl), and APS were higher than the cutoff values (0.79\/0.97\/0.50\/0.93, respectively). PC\u2010deficient plasma or PS\u2010deficient plasma mixed with normal plasma (25%\/50%\/75%\/100% PC or PS level) showed dose\u2010dependent decreases in the peak ratios (PC deficient: 0.85\/0.64\/0.44\/0.28; PS deficient: 0.69\/0.53\/0.40\/0.25), suggesting that the peak ratio at \u226450% of PC or PS level exceeded the cutoff value. The peak ratio in FV deficiency with FV \u226425% was higher than the cutoff value. FV\u2010deficient plasma spiked with 40\u2009IU\/dl rFV\u2010R506Q (FV<jats:sub>Leiden<\/jats:sub>) or rFV\u2010W1920R (FV<jats:sub>Nara<\/jats:sub>) showed &gt;90% peak ratios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>rTM\u2010mediated TF\u2010triggered CWA might be useful for screening PC pathway abnormality\u2010related thrombophilia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13777","type":"journal-article","created":{"date-parts":[[2022,4,17]],"date-time":"2022-04-17T16:04:15Z","timestamp":1650211455000},"page":"100-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Screening of the protein C pathway abnormality\u2010related thrombophilia by using thrombomodulin\u2010mediated tissue factor\u2010triggered clot waveform analysis"],"prefix":"10.1111","volume":"109","author":[{"given":"Naoki","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Department of 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