Major Haemorrhage during Vitamin K Antagonist Treatment: The Influence of Thyroid Hormone Levels

Background: Annually, approximately 1-3% of patients treated with vitamin K antagonists (VKA) suffer from major haemorrhage. Since high levels of free thyroxine (fT₄) are associated with increased thrombosis risk, the aim was to assess whether low levels of fT₄ contribute to major haemorrhage in patients under VKA treatment. Methods: The FACTORS (Factors in Oral Anticoagulant Safety) study is a case-control study on patients receiving VKA treatment, including 110 cases with major haemorrhage. Controls were 220 matched participants treated with VKA without major haemorrhage. Odds ratios (OR) and 95% confidence intervals (95% CI) for the association of fT₄ levels with major haemorrhage were calculated for different fT₄ cutoffs by conditional logistic regression. Results: In patients with an fT₄ level below 13 pmol/l, the risk of major haemorrhage was 5-fold increased (OR = 5.1; 95% CI: 0.9-28.6) compared with patients with an fT₄ level above 13 pmol/l. At a cutoff of 14 pmol/l, the risk was 3-fold increased (OR = 2.9; 95% CI: 1.0-8.5). High levels of fT₄ did not affect bleeding risk. No clear effect of thyroid-stimulating hormone and thyroid peroxidase antibodies was seen on the risk of major haemorrhage. Conclusions: These results indicate that fT₄ levels below 14 pmol/l play a role in the aetiology of major haemorrhage in VKA users.