{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:04:26Z","timestamp":1791515066601,"version":"4.3.4"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,8,25]]},"abstract":"\n Background<\/jats:title>\n \n Patients with mechanical heart valves (\n MHV<\/jats:styled-content>\n ) require warfarin to prevent thromboembolism. Although dabigatran was as effective as warfarin for stroke prevention in atrial fibrillation when compared with warfarin in patients with\n MHV<\/jats:styled-content>\n , the study was stopped early because of more strokes and bleeding with dabigatran. To determine why dabigatran was less effective than warfarin, we compared their effects on thrombin generation induced by\n MHV<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Thrombin generation in the absence or presence of valve leaflets or sewing ring segments (\n SRS<\/jats:styled-content>\n ) was quantified. Studies were done in control plasma, plasma depleted of factors (F)\n XII<\/jats:styled-content>\n ,\n XI,<\/jats:styled-content>\n or\n VII<\/jats:styled-content>\n , plasma containing varying concentrations of dabigatran, or plasma from patients on dabigatran or warfarin with varying dabigatran concentrations or international normalized ratio (\n INR<\/jats:styled-content>\n ) values. Mean endogenous thrombin potential (\n ETP<\/jats:styled-content>\n ) increased 1.2\u2010, 1.5\u2010, and 1.8\u2010fold in the presence of leaflets, Teflon\n SRS<\/jats:styled-content>\n , and Dacron\n SRS<\/jats:styled-content>\n , respectively. Whereas\n ETP<\/jats:styled-content>\n in\n FVII<\/jats:styled-content>\n \u2010depleted and control plasma was similar,\n ETP<\/jats:styled-content>\n was reduced to background levels in\n FXII<\/jats:styled-content>\n \u2010depleted plasma and abrogated in\n FXI<\/jats:styled-content>\n \u2010depleted plasma. Dabigatran had little effect on\n ETP<\/jats:styled-content>\n at concentrations below 400\u00a0ng\/\n mL<\/jats:styled-content>\n , whereas in plasma from warfarin\u2010treated patients,\n ETP<\/jats:styled-content>\n was suppressed with\n INR<\/jats:styled-content>\n values over 1.5.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n MHV<\/jats:styled-content>\n induce thrombin generation via the intrinsic pathway and generate sufficient thrombin to overwhelm clinically relevant dabigatran concentrations. In contrast, warfarin is more effective than dabigatran at suppressing\n MHV<\/jats:styled-content>\n \u2010induced thrombin generation. These data explain why dabigatran failed in\n MHV<\/jats:styled-content>\n patients and suggest that strategies targeting\n FXII<\/jats:styled-content>\n or\n FXI<\/jats:styled-content>\n may suppress the root cause of thrombosis in such patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.002322","type":"journal-article","created":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T21:19:48Z","timestamp":1440451188000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Dabigatran is Less Effective Than Warfarin at Attenuating Mechanical Heart Valve\u2010Induced Thrombin Generation"],"prefix":"10.1161","volume":"4","author":[{"given":"Iqbal H.","family":"Jaffer","sequence":"first","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Surgery, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Stafford","sequence":"additional","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Fredenburgh","sequence":"additional","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Whitlock","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Surgery, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I.","family":"Weitz","sequence":"additional","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.2.635"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199507063330103"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199106273242606"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2305"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(89)80690-4"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_3_4_8_2","unstructured":"(Canada) B\u2010I . 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