title: Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients.
abstract: Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Schaefer
authors.forename: Robert D
authors.initials: RD
authors.lastname: McBane
authors.forename: David F
authors.initials: DF
authors.lastname: Black
authors.forename: Lindsy N
authors.initials: LN
authors.lastname: Williams
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Moder
authors.affiliation: Waldemar E. Wysokinski, MD, Division of Cardiovascular Medicine, Mayo Clinic and Foundation for Education and Research, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 266 7231, Fax: +1 507 266 1617, E-mail: wysokinski.waldemar@mayo.edu.
authors.forename: Waldemar E
authors.initials: WE
authors.lastname: Wysokinski
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000150:complications*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000097:blood / Q000209:etiology; D000069604:Dabigatran; D057915:Drug Substitution; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D008642:Mesenteric Veins; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D011169:Portal Vein; D012008:Recurrence; D012189:Retrospective Studies; D000069552:Rivaroxaban; D013162:Splenic Vein; D020521:Stroke / Q000097:blood / Q000209:etiology*; D013876:Thiophenes / Q000627:therapeutic use*; D013923:Thromboembolism / Q000517:prevention & control; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology; D017211:Treatment Failure; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: Direct oral anticoagulants; antiphospholipid syndrome; thromboembolic complications; warfarin