The incidence of venous thromboembolism in patients with overt hyperthyroidism

Summary

Hyperthyroidism is associated with several changes in the haemostatic system resulting in a hypercoagulable state. It is uncertain at this stage whether this leads to an increased risk of venous thromboembolism (VTE). The aim of this retrospective cohort study was to determine the risk of VTE in all patients with overt hyperthyroidism and to compare this to the risk of VTE in the general population. In three hospitals in the Netherlands, patients with biochemically confirmed hyperthyroidism caused by Graves’ disease, multinodular goiter or toxic adenoma were included. All available electronic and handwritten records were examined. Primary outcome was the occurrence of VTE within six months before and until six months after the diagnosis of hyperthyroidism. We included a total of 587 patients. Five patients experienced a VTE during the study period, resulting in an incidence rate of 8.7 (95% CI 2.8 – 20.2) per 1,000 person-years. Three of these five patients had a first VTE (incidence rate for first VTE was 5.3 [95% CI 1.1 – 15.6] per 1,000 person-years). Incidence rates of VTE in the general population are between 0.6 and 1.6 per 1,000 person-years for first VTE and 0.7 and 1.8 per 1,000 person-years for all VTE. In conclusion, the incidence rate of VTE in patients with hyperthyroidism appears to be high. Future prospective studies are needed to further explore this possible association and to address its clinical implications.

Keywords

Hyperthyroidism - epidemiology - risk factor - venous thromboembolism

• References

• 1 Cushman M. et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004; 117: 19-25.
• 2 Naess IA. et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 05: 692-699.
• 3 Heit JA. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
• 4 Isma N. et al. Prospective analysis of risk factors and distribution of venous thromboembolism in the population-based Malmo Thrombophilia Study (MATS). Thromb Res 2009; 124: 663-666.
• 5 Rosendaal FR. Venous thrombosis: the role of genes, environment, and behavior. Hematology Am Soc Hematol Educ Program 2005; 1-12.
• 6 Debeij J. et al. The effect of changes in thyroxine and thyroid-stimulating hormone levels on the coagulation system. J Thromb Haemost 2010; 08: 2823-2826.
• 7 Erem C. et al. Blood coagulation and fibrinolysis in patients with hyperthyroidism. J Endocrinol Invest 2002; 25: 345-350.
• 8 Homoncik M. et al. Altered platelet plug formation in hyperthyroidism and hypothyroidism. J Clin Endocrinol Metab 2007; 92: 3006-3012.
• 9 Marongiu F. et al. Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. J Endocrinol Invest 1988; 11: 723-725.
• 10 Rogers JS. et al. Factor VIII activity and thyroid function. Ann Intern Med 1982; 97: 713-716.
• 11 Lippi G. et al. Hyperthyroidism is associated with shortened APTT and increased fibrinogen values in a general population of unselected outpatients. J Thromb Thrombolysis 2009; 28: 362-365.
• 12 Van Zaane B. et al. Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. Blood 2010; 115: 4344-4349.
• 13 Danescu LG. et al. Venous thromboembolism in patients hospitalized with thyroid dysfunction. Clin Appl Thromb Hemost 2009; 15: 676-680.
• 14 Lin HC. et al. Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5-year follow-up study. J Thromb Haemost 2010; 08: 2176-2181.
• 15 Anderson Jr FA. et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151: 933-938.
• 16 Ho WK. et al. The incidence of venous thromboembolism: a prospective, community-based study in Perth, Western Australia. Med J Aust 2008; 189: 144-147.
• 17 Nordstrom M. et al. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med 1992; 232: 155-1560.
• 18 Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83: 657-660.
• 19 Silverstein MD. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
• 20 Dagenais P. et al. A family study of the antiphospholipid syndrome associated with other autoimmune diseases. J Rheumatol 1992; 19: 1393-1396.
• 21 Hofbauer LC. et al. Graves’ disease associated with the primary antiphospholipid syndrome. J Rheumatol 1996; 23: 1435-1437.
• 22 Khochtali I. et al. Graves’ disease associated with cerebrovascular disease and anti-phospholipid antibody syndrome. Int J Endocrinol. 2010 epub ahead of print
• 23 Nabriski D. et al. Autoimmune thyroid disease and antiphospholipid antibodies. Am J Hematol 2000; 64: 73-75.