Review Article The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors A systematic review and meta-analysis Danka J. F. Stuijver 1,2 ; Bregje van Zaane 1,2 ; Erica Romualdi 3 ; Dees P. M. Brandjes 1,2 ; Victor E. A. Gerdes 1,2 ; Alessandro Squizzato 3 1 Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands; 2 Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; 3 Department of Clinical Medicine, University of Insubria, Varese, Italy Summary Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo. Data sources included MEDLINE (2006–2012), EMBASE (2006–2012), and reference lists. The sources were combined with our previous search containing studies from 1980–2006. Eligible studies were all observational or experimental studies. Two investigators inde- pendently extracted data and rated study quality. Weighted mean pro- portion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consist- ing of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after Correspondence to: Danka J. F. Stuijver Department of Internal Medicine Slotervaart Hospital Louwesweg 6, Amsterdam 1066 EC, The Netherlands Tel.: +31 20 5125194, Fax: +31 20 5124783 E-mail: d.j.stuijver@amc.uva.nl treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrino- lytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in en- dogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hy- perthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis. Keywords Thyrotoxicosis, hyperthyroidism, coagulation, fibrinolysis Received: July 18, 2012 Accepted: August 10, 2012 Prepublished online: September 26, 2012 doi:10.1160/TH12-07-0496 Thromb Haemost 2012; 108: 1077–1088 1077 © Schattauer 2012 Thrombosis and Haemostasis 108.6/2012 Introduction Hyperthyroidism is associated with a hypercoagulable state (1, 2). Several coagulation and fibrinolytic parameters appear to be af- fected by thyrotoxicosis; elevated plasma levels of factor VIII (FVIII), factor IX (FIX), von Willebrand factor (VWF), and fibri- nogen, and a reduced fibrinolytic activity due to increased levels of plasminogen activator inhibitor-1 (PAI-1) have been reported in both hyperthyroid patients and healthy subjects after taking thy- roid hormones (1, 3–9). However, in a previous systematic review, we found the majority of these studies to have major methodologi- cal flaws (1). This left the net effect of thyroid hormone excess on the haemostatic system unclear. Moreover, the question as to whether thyrotoxicosis enhances the risk of venous thrombosis, and to which extent, still remains controversial. In this review, we aimed to update our previous systematic re- view and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibri- nolytic system in vivo (1). For the interpretation of the results we will also discuss the recent studies on the relationship between (supra) physiological thyroid hormone levels and VTE. Methods Study identification A computer-assisted search of the MEDLINE and EMBASE elec- tronic databases from July 2006 to March 2012 was performed to identify published studies that evaluated the effect of thyroid hor- mone excess on the coagulation-fibrinolytic system. The following search terms were used for the MEDLINE search: “haemostasis, blood coagulation tests, blood coagulation, blood coagulation fac- For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.thrombosis-online.com on 2012-12-06 | ID: 1000467415 | IP: 128.104.209.210