title: Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome.
abstract: BACKGROUND
  Long-term anticoagulation is recommended in antiphospholipid syndrome with thrombosis in order to prevent recurrences. While the current mainstay relies on vitamin K antagonists, their long-term maintenance may remain challenging.
  
  
  OBJECTIVE
  To report on the safety and the efficacy of oral direct inhibitors of thrombin and factor Xa (ODIs) in antiphospholipid syndrome (APS).
  
  
  METHODS
  We performed a descriptive analysis of patients with APS enrolled in a French multicentre observational cohort between January 2012 and March 2014 and receiving ODIs. The main outcomes were the occurrence of a thrombotic recurrence or bleeding events.
  
  
  RESULTS
  Twenty-six patients with APS (primary in 12) received ODIs. Twenty patients had been previously treated with VKA (n=19), or fondaparinux (n=1) for a median duration of 3years. ODIs were introduced as second-line therapy because of INR lability/therapeutic simplification (n=17), recurrent thrombosis (n=1), VKA's associated bleeding event (n=1), and atrial fibrillation (n=1). Six patients received ODIs as first-line therapy. After a median [IQR] follow-up of 19 [8-29] months, one relapse of arterial thrombosis, two bleeding events (hypermenorrhea and rectal bleeding under rivaroxaban) and one recurrent migraine were reported, leading to discontinuation of therapy in these 4 patients.
  
  
  CONCLUSIONS
  ODIs might be an alternative therapeutic option in APS. Prospective studies are warranted to evaluate their safety in this condition.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaire Paris Sud, CHU Bicêtre, Service de Médecine Interne et Immunologie Clinique, Le Kremlin Bicêtre, France; Université Paris Sud, UMR 1184, Le Kremlin Bicêtre, France.
authors: Nicolas
authors: N
authors: Noel
authors: Hôpital d'Instruction des Armées Percy, Service de Médecine Interne, Clamart, France.
authors: Fabien
authors: F
authors: Dutasta
authors: AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Service de Médecine Interne Pôle médecine, Paris, France; Université René Descartes, Paris 5, France. Electronic address: nathalie.costedoat@gmail.com.
authors: Nathalie
authors: N
authors: Costedoat-Chalumeau
authors: CHRU de Caen, Service de Médecine Interne, Caen, France.
authors: Boris
authors: B
authors: Bienvenu
authors: Université Paris Sud, UMR 1184, Le Kremlin Bicêtre, France; AP-HP, Hôpitaux Universitaires Paris Sud, CHU Bicêtre, Service de Rhumatologie, Le Kremlin Bicêtre, France.
authors: Xavier
authors: X
authors: Mariette
authors: CH Lisieux, Service de Médecine Interne, Lisieux, France.
authors: Loik
authors: L
authors: Geffray
authors: AP-HP, Groupe Hospitalier Lariboisière-Fernand Widal, Service de Médecine Interne 2, Paris, France.
authors: Damien
authors: D
authors: Sene
authors: CHU Poitiers, Service de Médecine Interne, Poitiers, France.
authors: Rafik Bekhadj
authors: RB
authors: Chaidi
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaire Paris Sud, CHU Bicêtre, Service de Médecine Interne et Immunologie Clinique, Le Kremlin Bicêtre, France.
authors: Jean-Marie
authors: JM
authors: Michot
authors: AP-HP, CHU Saint Antoine, Service de Médecine Interne, France.
authors: Olivier
authors: O
authors: Fain
authors: AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
authors: Luc
authors: L
authors: Darnige
authors: AP-HP, Hôpital Pitié-Salpétrière, Service d'Hématologie Biologique, France.
authors: Annick
authors: A
authors: Ankri
authors: AP-HP, Hôpital Pitié-Salpêtrière, Centre national de référence maladies auto-immunes systémiques rares, Département de Médecine Interne et Immunologie Clinique, Paris, France; DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, Faculté Paris 6, France.
authors: Patrice
authors: P
authors: Cacoub
authors: AP-HP, Hôpital Pitié-Salpêtrière, Centre national de référence maladies auto-immunes systémiques rares, Département de Médecine Interne et Immunologie Clinique, Paris, France; DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, Faculté Paris 6, France.
authors: Jean-Charles
authors: JC
authors: Piette
authors: AP-HP, Hôpital Pitié-Salpêtrière, Centre national de référence maladies auto-immunes systémiques rares, Département de Médecine Interne et Immunologie Clinique, Paris, France; DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, Faculté Paris 6, France. Electronic address: david.saadoun@psl.aphp.fr.
authors: David
authors: D
authors: Saadoun
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000188:drug therapy*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D013917:Thrombin; D015951:Factor Xa
keywords: Antiphospholipid syndrome; Dabigatran; Oral direct inhibitors; Rivaroxaban; Thrombosis