title: The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate.
abstract: Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 ± 10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients' HTI levels were very variable (DE110, 10-90th percentile: 20.5-223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan-Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels.
authors.affiliation: aDivision of Cardiology, Department of Medicine, Taipei Veterans General HospitalbInstitute of Clinical Medicine and Cardiovascular Research Institute, National Yang-Ming UniversitycDepartment of Neurology, Taipei Veterans General HospitaldDepartment of Critical Care Medicine, Taipei Veterans General HospitaleDivision of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Hu
authors.forename: Jo-Nan
authors.initials: JN
authors.lastname: Liao
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Chern
authors.forename: Yenn-Jiang
authors.initials: YJ
authors.lastname: Lin
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.forename: Cheng-Hsueh
authors.initials: CH
authors.lastname: Wu
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Sung
authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Wang
authors.forename: Tse-Min
authors.initials: TM
authors.lastname: Lu
authors.forename: Tze-Fan
authors.initials: TF
authors.lastname: Chao
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.forename: Li-Chi
authors.initials: LC
authors.lastname: Hsu
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chung
authors.forename: Peter M-H
authors.initials: PM
authors.lastname: Chang
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Chuen-Wang
authors.initials: CW
authors.lastname: Chiou
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001777:Blood Coagulation / Q000187:drug effects*; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D016016:Proportional Hazards Models; D011517:Prothrombin Time; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D000991:Antithrombins; D000069604:Dabigatran