Impaired release of tissue plasminogen activator from the endothelium in Graves' disease - indicator of endothelial dysfunction and reduced fibrinolytic capacity

Background Patients with hyperthyroidism have increased plasma levels of vo n Willebrand factor (vWF). Changes in tissue plasminogen activator (t-PA) a nd plasminogen activator inhibitor (PAI-I), another two endothelium-derived proteins and modulators of blood fibrinolytic activity, have not been repo rted in hyperthyroidism. Methods The release of t-PA by vascular endothelial cells after venous occl usion, basal blood concentrations of t-PA, PAI-1 and vWF were studied in 33 patients with hyperthyroidism, with most of them followed up 30 days after iodine radiotherapy. Results Compared with control subjects, both the basal t-PA levels in plasm a and the increase in t-PA levels with venous occlusion were significantly decreased in patients (P < 0 . 001), whereas plasma PAI-1 and vWF levels we re increased greatly (P < 0 . 001). At follow-up, patients with normal plas ma free thyroxine (T-4) and total tri-iodothyronine (T-3) showed similar pl asma levels of t-PA, PAI-1, vWF and release of t-PA from endothelial cells as the control subjects (P > 0 . 05). In those with persistent elevated T-4 or T-3 levels, however, the basal plasma t-PA level and the released t-PA from endothelial cells during venous occlusion were significantly lower tha n in the control subjects (P < 0 . 001 and P < 0 . 005), and blood concentr ations of PAI-1 and vWF did not return to the normal range (P < 0 . 001 and P < 0 . 001). In all patients, serum thyroid hormone concentrations were i nversely correlated with basal plasma t-PA (T-4: r = -0 . 549, P < 0 . 001; T-3: r = -0 . 463, P < 0 . 001) and released t-PA by endothelial cells (T- 4: r= -0 . 505, P < 0 . 001; T-3: r= -0 . 450, P < 0 . 001) but strongly co rrelated with plasma PAI-1 (T-4: r = 0 . 613, P < 0 . 001; T-3: r = 0 . 577 , P < 0 . 001) and vWF (T-4: r = 0 . 457, P < 0 . 001; T-3: r = 0 . 564, P < 0 . 001). Conclusion Hyperthyroid patients may experience vascular endothelial dysfun ction and reduced fibrinolytic activity in blood.