title: Alterations in coagulation and fibrinolysis after levothyroxine exposure in healthy volunteers: a controlled randomized crossover study.
abstract: BACKGROUND
  Several hemostatic abnormalities have been reported in hyperthyroidism, but the overall effect of thyroid hormone excess on coagulation and fibrinolysis is unclear.
  
  
  OBJECTIVE
  Our aim was to assess whether the use of supraphysiological doses of levothyroxine leads to coagulation activation and inhibition of fibrinolysis.
  
  
  METHODS
  Healthy volunteers were randomized to receive levothyroxine or no medication for 14 days with a washout period of at least 28 days in a crossover design. To study the effects of different degrees of thyroid hormone excess, 16 participants received levothyroxine in a dose of 0.3 mg per day, and 12 received levothyroxine 0.45 or 0.6 mg per day depending on body weight. Several variables of coagulation and fibrinolysis were measured.
  
  
  RESULTS
  Levels of von Willebrand factor activity (VWF:RiCo) and antigen (VWF:Ag), factor (F) VIII, plasminogen activator inhibitor-1 (PAI-1) and clot-lysis time were slightly higher after levothyroxine 0.3 mg per day than after the control situation, but only levels of VWF showed a significant increase from baseline. After levothyroxine 0.45 or 0.6 mg per day, levels of fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, FVIII by 19%, FIX by 14%, FX by 7%, PAI-1 by 116% and clot-lysis time by 14%, and activated partial thromboplastin time decreased by 3%; all were significant changes compared with the control situation. We did not observe clear evidence of coagulation activation.
  
  
  CONCLUSIONS
  Our data suggest that thyroid hormone excess increases coagulation factor levels and inhibits fibrinolysis in a dose-dependent fashion. This implies an increased risk of venous thrombosis during hyperthyroidism.
authors: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands. b.vanzaane@amc.uva.nl
authors: B
authors: B
authors: Van Zaane
authors: A
authors: A
authors: Squizzato
authors: J
authors: J
authors: Debeij
authors: O M
authors: OM
authors: Dekkers
authors: J C M
authors: JC
authors: Meijers
authors: A P
authors: AP
authors: Van Zanten
authors: H R
authors: HR
authors: Büller
authors: V E A
authors: VE
authors: Gerdes
authors: S C
authors: SC
authors: Cannegieter
authors: D P M
authors: DP
authors: Brandjes
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000150:complications; D008297:Male; D012307:Risk Factors; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage / Q000009:adverse effects*; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D001779:Blood Coagulation Factors; D013963:Thyroid Hormones; D013974:Thyroxine