{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:32:28Z","timestamp":1762299148687},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007602","name":"Programme Grants for Applied Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Protein C (PC) deficiency results in dysregulated thrombin generation and increases thrombosis risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In order to investigate the potential effects of anticoagulant drugs in PC deficiency, we evaluated the pharmacodynamic effect of selective direct factor (F) IIa inhibitors (dabigatran and argatroban), selective direct FXa inhibitors (rivaroxaban and apixaban) and an indirect FXa\/FIIa inhibitor (enoxaparin) in commercial PC\u2010deficient plasma using thrombin generation and viscoelastometry assays modified to reflect PC anticoagulant activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endogenous thrombin potential (ETP) and peak thrombin concentration (PTC) were increased in PC\u2010deficient plasma but this corrected completely with PC concentrate. Inhibition of FIIa and FXa with the selective inhibitors also corrected the increased ETP and PTC but required high drug concentrations. There was sustained low\u2010level thrombin generation in PC\u2010deficient plasma with FXa inhibitors but not with FIIa inhibitors. Adding PC concentrate to PC\u2010deficient plasma anticoagulated with dabigatran had little additional effect on ETP or PTC. In contrast, addition of even small quantities of PC concentrate to PC\u2010deficient plasma anticoagulated with rivaroxaban further diminished ETP, primarily by abolishing sustained thrombin generation. In the viscoelastometry assay, the coagulation time was shortened and \u03b1\u2010angle increased in PC\u2010deficient plasma. These abnormalities reversed with both dabigatran and rivaroxaban.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The selective direct FXa and FIIa inhibitors at high concentrations both counteracted the abnormal thrombin generation and clot formation observed in PC\u2010deficient plasma, but with qualitative differences in their effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13126","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T16:16:33Z","timestamp":1574439393000},"page":"126-133","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential effects of direct factor IIa and factor Xa inhibitors in protein C\u2010deficient plasma detected using thrombin generation and viscoelastometry assays"],"prefix":"10.1111","volume":"42","author":[{"given":"Riyaad","family":"Aungraheeta","sequence":"first","affiliation":[{"name":"School of Cellular 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