Alterations in Coagulation and Fibrinolysis after Levothyroxine Exposure in Healthy Volunteers: A Controlled Randomized Crossover Study.
J Thromb Haemost. 2011 Jul 5. Epub 2011 Jul 5. PMID: 21729238
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands Department of Vascular Medicine, Academic Medical Center, Amsterdam,
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. Patients/Methods: Healthy volunteers were randomized to receive levothyroxine or no medication for 14 days with a wash-out 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/day, and 12 received levothyroxine 0.45 or 0.6 mg/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/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/day, levels of fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, factor VIII by 19%, factor IX by 14%, factor X by 7%, PAI-1 by 116%, clot-lysis time by 14%, and activated partial thromboplastin time decreased by 3%; all significant changes compared to 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.