Background: Hyperthyroidism is associated with an increased risk of atherothrombosis and venous thrombotic events by mechanisms that are not fully understood. Previous work has shown that blood clot structure determines the susceptibility to thrombosis and therefore the aim of this study was to investigate the effects of hyperthyroidism on clot structure and fibrinolysis.
Methods: Six patients with hyperthyroidism were included in a pilot longitudinal study. Blood samples were collected in the hyperthyroid phase and after rendering the patients euthryoid. All patients received carbimazole treatment and one patient was also treated with radioactive iodine. Clotting of plasma samples was triggered ex vivo by the addition of thrombin and clot structure was subsequently investigated by permeation and turbidity analyses. Fibrinolysis was studied using turbidity analysis by adding tissue plasminogen activator and plasminogen to the clotting reaction.
Results: On presentation, mean free T4 (95% CI) was 67.6 pmol/L (43.092.3), falling to 17.9 pmol/L (15.919.9) post-treatment. Permeation was calculated using the Darcy constant (Ks), which represents the surface of the clot that allows flow through a fibrin network. Mean Ks of samples during the hyperthyroid phase was 4.2×10−9 cm2 (3.64.9) compared with post treatment Ks of 5.2×10−9 cm2 (4.55.9; P=0.002). Clots formed during hyperthyroidism were associated with higher maximum absorbance of 0.66 (0.600.72) compared with clots formed during euthyroidism [0.58 (0.550.60); P=0.045]. In the hyperthyroid phase, clots took 638 seconds (515761) to achieve 50% lysis compared with 510 seconds (435585; P=0.026) when patients were euthyroid.
Conclusions: The lower Ks, higher final turbidity and resistance to lysis indicate the formation of compact and tight fibrin clot networks in hyperthyroidism.
This study demonstrates, for the first time, a prothrombotic clot structure in patients with hyperthyroidism, which may explain, at least in part, the increased thrombotic risk seen in these individuals.