Effects of thyroid function on hemostasis, coagulation, and fibrinolysis: a Mendelian Randomization study

BACKGROUND: Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on hemostasis, coagulation, and fibrinolysis are unknown. METHODS: In a two sample Mendelian Randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism (N=134,641), normal-range TSH (N=54,288) and fT4 (N=49,269), hyperthyroidism (N=51,823), and thyroid peroxidase antibody positivity (TPOAb) (N=25,821) on coagulation (APTT, VWF, factor VIII, PT, factor VII, fibrinogen) and fibrinolysis (D-dimer, TPA, PAI1) from the CHARGE Hemostasis Consortium (N=2,583-120,246). Inverse-variance-weighted random effects was the main MR analysis followed by sensitivity analyses. Two-sided p<0.05 was nominally significant and p