ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 OC3.7

Thyroid dysfunction and clot structure: a mechanism for increased thrombotic risk in hyperthyroid individuals?

Jonathan Hooper1, Steve Orme2, Bregje van Zaane3, Katharina Hess1, Saad Alzahrani1, Kristina Standeven1, Simon Pearce4, Peter Grant1 & Ramzi Ajjan1,2


1Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, West Yorkshire, UK; 2Department of Endocrinology, Leeds Teaching Hospital NHS Trust, Leeds General Infirmary, Leeds, West Yorkshire, UK; 3Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands; 4Institute of Human Genetics, International Centre for Life, Newcastle-upon-Tyne, UK.


Hyperthyroidism is associated with increased thrombotic risk through mechanisms that are not fully understood. In contrast, a tendency to bleeding has been reported in hypothyroidism. Fibrin network structure has been shown to determine susceptibility to atherothrombosis and venous thrombotic events and therefore, this study investigates the effects of thyroid-dysfunction on clot structure and fibrinolysis using longitudinal interventional studies.

Seventeen hyperthyroid patients were recruited (mean age 39.41±2.6) and treated with antithyroid medication until euthyroid. Twenty hypothyroid subjects were also recruited (mean age 49.6±14.8) and treated with L-T4. In both groups, blood samples were taken at baseline and after normalisation of thyroid function. Coagulation-fibrinolysis characteristics were investigated ex vivo using a validated turbidimetric assay and the following parameters studied: i) lag phase (LP): indicating thrombotic tendency, ii) maximum absorbance (MA) measuring clot density, iii) time to 50% lysis (L50%), assessing fibrinolytic potential, iv) Lysis area (LA), measuring the balance between clot formation and lysis. Plasma levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP) and complement C3 were also measured.

LP was 612±21.1 in hyperthyroid subjects, increasing to 709±23 s after normalising thyroid function (P=0.001), whereas MA fell from 0.43±0.03 to 0.36±0.02 a.u. (P=0.009). LA was larger at baseline than post treatment (246±26.4 and to 164±22, respectively; P=0.02). Fibrinogen, PAI-1 and C3 levels were all higher in the hyperthyroid phase. In contrast, hypothyroid subjects had longer LP at baseline compared with post-normalisation of thyroid function (354±13 and 321±7 s, respectively; P=0.005), whereas MA increased from 0.32±0.02 to 0.36±0.02 (P=0.008).

Hyperthyroid patients have a procoagulant tendency, with short lag phase, compact clot structure and impaired-lysis, whilst the opposite is true in hypothyroidism. We suggest that altered clot structure in hyperthyroid subjects is responsible, at least in part, for increased thrombotic risk in this population.