Prothrombotic alterations in plasma fibrin clot properties in thyroid disorders and their post-treatment modifications

Abstract

Introduction: Available data on fibrin clot properties and fibrinolysis in hyperthyroidism and hypothyroidism are inconsistent. Our objective was to assess the impact of effective treatment of hyper- and hypothyroidism on fibrin clot characteristics.

Material and methods: In a case-control study, ex vivo plasma fibrin clot permeability (Ks) and efficiency of fibrinolysis were assessed in 35 consecutive hyperthyroid and 35 hypothyroid subjects versus 30 controls. All measurements were performed before and after 3months of thyroid function normalizing therapy.

Results: At baseline, hyperthyroid, but not hypothyroid, patients had lower Ks than controls (p<0.0001). Hyperthyroid and hypothyroid groups compared with controls had prolonged clot lysis time (CLT), and lower rate of D-dimer release from clots (D-Drate) (all p<0.05). The regression analysis adjusted for fibrinogen showed that in hyperthyroid patients, pre-treatment thyroid stimulating hormone (TSH) independently predicted Ks, while thrombin activatable fibrinolysis inhibitor (TAFI) antigen predicted CLT. In hypothyroid individuals a similar regression model showed that TSH independently predicts CLT. After 3months of thyroid function normalizing therapy, 32 (91.4%) hyperthyroid and 30 (85.7%) hypothyroid subjects achieved euthyroidism and had improved fibrin clot properties (all p<0.05), with normalization of Ks in hyperthyroid and lysability in hypothyroid patients.

Conclusions: Both hyper- and mild-to-moderate hypothyroidism are associated with prothrombotic plasma fibrin clot phenotype and restoration of euthyroidism improves clot phenotype. Abnormal fibrin clot phenotype might contribute to thromboembolic risk in thyroid disease.

Keywords: TAFI; fibrin clot; fibrinolysis; hyperthyroidism; hypothyroidism; thrombin activatable fibrinolysis inhibitor.