Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism

T-4 levels are determinant of several components of the fibrinolytic system . However, relationships between hypothyroidism and alteration of fibrinoly tic capacity are not well established, and published data remain conflictin g. As the impact of hypothyroidism on both degradation and synthesis of pro teins may vary according to the severity of the disease, we measured fibrin olytic activity across varying states of hypothyroidism. We measured fibrin ogen, D-dimers (DDI), alpha (2)-antiplasmin activity, tissue plasminogen ac tivator antigen (t-PA Ag), plasminogen, plasminogen activator inhibitor ant igen (PAI-1 Ag), and factor XII (FXII) of the coagulation. We prospectively included 76 middle-aged female subjects: 25 controls, 24 patients displayi ng moderate hypothyroidism (TSH, 10-50 mU/L), and 27 patients with severe h ypothyroidism (TSH, >50 mU/L). Blood pressure, body mass index, smoking hab its, total cholesterol as well as high and low density lipoprotein subfract ions, triglyceride, fasting glycemia, and insulinemia were recorded. We found a different pattern of fibrinolytic abnormalities according to the severity of hypothyroidism. Compared with controls, patients with moderate hypothyroidism displayed a decreased fibrinolytic activity, as reflected b y lower DDI levels, higher alpha (2)-antiplasmin activities, and higher lev els of t-PA and PAI-1 Ag. In sharp contrast, patients with severe hypothyro idism exhibited higher DDI levels, lower alpha (2)-antiplasmin activities, and lower t-PA and PAI-1 Ag levels. These results were not accounted for by confounding factors such as age, smoking, and components of the insulin re sistance syndrome. Free T-4 was significantly associated with fibrinogen, a lpha (2)-antiplasmin, PAI-1 Ag, total cholesterol, and triglyceride and was negatively associated with DDI. The main hypotheses underlying the mechani sms by which thyroid status may affect the fibrinolytic system remain to be established. In conclusion, patients with moderate hypothyroidism, who were consistently shown to be at high risk for cardiovascular disease, have decreased fibrin olytic activity. Subjects with severe hypothyroidism have a tendency toward increased fibrinolytic activity, and these modifications may participate t o the bleeding tendency observed in such patients.