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.
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands.
Jan
J
Debeij
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands ; Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands.
Suzanne C
SC
Cannegieter
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands ; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
Bregje
B
van Zaane
Department of Clinical Biochemistry, Slotervaart Hospital, Amsterdam, The Netherlands.
Anton P
AP
van Zanten
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands ; Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands ; Department of Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands.
Frits R
FR
Rosendaal
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands ; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
Victor E A
VE
Gerdes
Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands ; Department of Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands.
Pieter H
PH
Reitsma
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands ; Department of Endocrinology and Metabolism, Leiden University Medical Centre, Leiden, Amsterdam, The Netherlands.
Olaf M
OM
Dekkers
Coagulation; Epidemiology; Free thyroxine; Haemorrhage; Vitamin K antagonists