Is a Hypercoagulable State Present in Hypothyroidism?

Haemostasis in hypothyroidism has been widely investigated as far as regards a mild bleeding tendency. In fact several papers on the abnormalities of platelet function and coagulant factors have been published in this field (1). However, apparently in contrast, the question of whether hypothyroidism predisposes to ischaemic heart disease has been debated. In fact autopic findings have shown a significantly higher incidence of coronary artery disease in either overt or subclinical hypothyroidism, although the incidence of myocardial infarction did not increase proportionately (2). Howev er, a definitive study examining the incidence of atherosclerosis in myxedematous patients before and after treatment is still lacking (3). For this reason we decided to investigate thrombin and plasmin activity in hypothyroid patients in the attempt to determine whether an unbalance between coagulation and fibrinolysis could be present in hypothyroid patients. For this purpose we assayed Fibrinopeptide A (FPA) and Fibrinopeptide Bp 15-42 (BB), sensitive indicators of thrombin and plasmin activity in vivo respectively. Particularly, FPA is a product of thrombin action upon the A chains of fibrinogen (4) while BB is cleaved by plasmin from the N-terminal end of the fibrin(ogen) BB chains (5). Moreover we calculated the ratio between BB and FPA (BB/FPAr), which is thought to be a reliable index of the balance between coagulation and fibrinolysis (6). We studied 27 patients (24 F and 3 M, mean age 48.4 + 12.8 years) with overt untreated hypothyroidism, recognized on the basis of clinical grounds and a decrease in total serum thyroid hormone concentration (TI3, TT4, Spac T3 and Spac T4, Byk Mallinckrodt, Milan, Italy) and an increase in serum TSH values (Becton Dickinson SpA, Milan, Italy). Diagnoses were as follows: Hashimoto's thyroiditis: n_ 15; Idiopathic Thyroid Atrophy: n 9; Thyroidectomy: n 3. Patients were not affected by cardiovascular, hepatic or renal disease and had not taken drugs affecting haemostasis for at least 2 weeks. TSH values ranged from 4.6 to 108 pU/l (reference range 0.2-4 pu/l). FPA and BB 15-42 levels were measured by radioimmunoassay (4, 5) (Mallinckrodt, usA and IMCO, Sweden) on plasma from which fibrinogen had been absorbed with bentonite for the FPA assay (7) or with ethanol for the BB 15-42 assay (5). Radioiodination (t"I) of BB 15-42 was carried out by Sorin Biomedica (Saluggia, Italy). The patients were carefully compared to 23 apparently healthy subjects sexand age-matched. For statistical evaluation of the data the Mann-Whitney U-test was employed; values are expressed as median and 95% confidence intervals of the median. The results are shown in Thble 1. FPA and BB levels were higher in hypothyroid patients than in controls (p 0.0001). Bp/ FPAr values were higher in controls than in hypothyroid patients (p 0.00e). In our patients we found an increased thrombin activity, which may be responsible for an excessive intravascular fibrin formation. Plasmin activity was also increased in our patients, confirmirg previous findings (8, 9, 10), probably as a homoeostatic mechanism, in which fibrin deposition due to enhanced thrombin activity is counterbalanced by fibrin dissolution secondary to increased plasmin activity (11) . However, in our patients increased plasmin activity does not seem to counterbalance