Jiri Horacek1, Jaroslav Maly2, Ioannis Svilias2, Lukas Smolej2, Jitka Cepkova2, Jaroslav Vizda2, Petr Sadilek2, Ilona Fatorova2, Pavel Zak2. 1. 4 Department of Internal Medicine - HaematologyDepartment of Nuclear MedicineCharles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic jiri.horacek@fnhk.cz. 2. 4 Department of Internal Medicine - HaematologyDepartment of Nuclear MedicineCharles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic.
Abstract
OBJECTIVE: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.
OBJECTIVE: With increasing freethyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.
Authors: Christina Ellervik; Samia Mora; Aleksander Kuś; Bjørn Åsvold; Eirini Marouli; Panos Deloukas; Rosalie B T M Sterenborg; Alexander Teumer; Stephen Burgess; Maria Sabater-Lleal; Jennifer Huffman; Andrew D Johnson; David-Alexandre Trégouet; Nicolas L Smith; Marco Medici; Paul S DeVries; Daniel I Chasman; Alisa D Kjaergaard Journal: Thyroid Date: 2021-08-05 Impact factor: 6.506