title: Interactions of bexarotene (LGD1069, Targretin) with the coagulation system.
abstract: OBJECTIVE
  Bexarotene, (LGD1069, Targretin), is an antitumoral agent used as chemotherapy in the treatment of cutaneous T-cell lymphoma. Therapy with bexarotene is accompanied by adverse events, such as, bleeding, hemorrhage, and coagulopathy
  
  
  OBJECTIVE
  In order to design applications for bexarotene, it was very important to gain an understanding of how bexarotene inhibits blood clotting
  
  
  METHODS
  We investigated the interaction between bexarotene or vehicle alone, and coagulation factors or blood cells. We used both in vitro and in vivo assays. Anticoagulant activity of bexarotene or vehicle was assessed by clotting time tests (TT, RT, APTT, and PT). Coagulation factors activity was measured by adding diluted test plasma to artificially prepared factor-deficient plasma. Direct interactions between bexarotene and factor Xa were studied by chromogenic substrate assay. A mouse model was used to investigate in vivo effects of the drug on blood system and for evaluation of clinical hematology and organ pathology.
  
  
  RESULTS
  Increases in clotting times (prothrombin time and activated thromboplastin time) occurred with bexarotene in in vitro and in vivo experiments. We detected no significant influence of bexarotene on factors II, V, VII, VIII, XI and XII, while factor IX and factors X were affected. Bexarotene exerts anticoagulant effects and acts mainly as a direct factor IX and factor X inhibitor. On the contrary, the vehicle is remarkably inert toward the coagulation system. The number of blood cells was unaffected in mice treated with bexarotene or with the vehicle.
  
  
  CONCLUSIONS
  Monitoring of the coagulation factors profile should be considered in cancer patients receiving bexarotene, particularly those with a known diagnosis of coagulation factors deficient.
authors.affiliation: Laboratoire de Recherches sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires UMR CNRS 7149, Université Paris Val de Marne, Avenue du Général de Gaulle, 94010, Créteil cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Hespel
authors.forename: Najet
authors.initials: N
authors.lastname: Mejdoubi-Charef
authors.forename: Said
authors.initials: S
authors.lastname: Yous
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: Dulce
authors.initials: D
authors.lastname: Papy-Garcia
authors.forename: Said
authors.initials: S
authors.lastname: Charef
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D000077610:Bexarotene; D001777:Blood Coagulation / Q000187:drug effects*; D016903:Drug Monitoring; D005164:Factor IX / Q000037:antagonists & inhibitors*; D005170:Factor X / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D051379:Mice; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D013764:Tetrahydronaphthalenes / Q000633:toxicity*
chemical_list: D016588:Anticarcinogenic Agents; D013764:Tetrahydronaphthalenes; D005164:Factor IX; D005170:Factor X; D000077610:Bexarotene