An Increase in Thyroid Hormone Levels Is Associated with a Pro-Coagulation Shift in Hemostatic Balance

Presentation Number: SAT-0555
Date of Presentation: June 21st, 2014

Jiri Horacek*, Jaroslav Maly, Ioannis Svilias, Jaroslav Vizda and Pavel Zak
Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic


With increasing free T4 levels, a gradually rising risk of venous thromboembolism has been described in case-control studies (1,2). However, the reports on the influence of thyroid hormones on coagulation and fibrinolysis, while suggesting a hypercoagulable state in thyrotoxicosis, have only been rare and often of low methodological quality (3). In hyperthyroidism, an increase in fibrinogen (FBG), von Willebrand factor (VWF), factor VIII (FVIII) and plasminogen activator inhibitor (PAI) as well as a decrease in tissue type-plasminogen activator (t-PA), have repeatedly been described, while for other factors the results were inconclusive.

We analyzed multiple markers of hemostasis in a cohort of patients shifting from severe hypothyroidism to mild hyperthyroidism during their differentiated thyroid cancer treatment. As cancer itself influences the coagulation system we excluded those with possible residual disease (i.e. a measurable thyroglobulin level during follow up). In 90 patients following total thyroidectomy for cancer, multiple tests were performed on two occasions: (a) before radioiodine remnant ablation, i.e. in hypothyroidism (TSH, median 109.6 mIU/L; interquartile range (IQR) 78.6-141.9, reference range (RR) 0.15-5.0 ), and (b) 6 to 8 weeks later on levothyroxine treatment, with low-normal to suppressed TSH (median 0.14 mIU/L; IQR 0.04-0.50). Wilcoxon test for paired data was used for comparisons.

During levothyroxine treatment, a significant increase in FBG from median 3.4 to 3.8 g/L (p<0,001; RR 2.0-4.0), in VWF from median 85 to 127 % (p<0,001; RR 50-160), in FVIII from median 111 to 148 % (p<0,001; RR 60-150), and in PAI from median 6.5 to 13.9 ug/L (p<0,001; RR 1.0-25.0) was observed. As a novel finding, the activation times of primary hemostasis (i.e. platelet adhesion and aggregation), evaluated by the PFA-100 System after stimulation with collagen and epinephrine or ADP, were significantly shortened; for epinephrine from median 148 to 117 s (p<0,001; RR 75-145) and for ADP from median 95 to 80 s (p<0,001; RR 62-104). We did not confirm a significant decrease in t-PA (2.1 to 2.0 ug/L; p = 0.380, RR 1.0-10.0) or an increase in D-dimer (0.32 to 0.30 mg/L; p = 0.463, RR 0.0-0.5).

Still, these results together suggest that an increase in thyroid hormones shifts the hemostatic balance towards a hypercoagulable and hypofibrinolytic state. This may contribute to the increased cardiovascular mortality observed in (even mild) thyrotoxicosis (4).


Nothing to Disclose: JH, JM, IS, JV, PZ