Prothrombotic changes due to an increase in thyroid hormone levels

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 (LT 4 ) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. Results: During LT 4 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 mg/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.

The influence of thyroid function on the coagulation system and its clinical consequences

“…Concomitantly, plasminogen, the main enzyme promoting fibrinolysis, was decreased. Others investigated patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment and showed in vitro that during levothyroxine treatment, the activation times of platelet adhesion and aggregation after stimulation with collagen and epinephrine/adenosine‐diphosphate were significantly shortened . The previously shown effects of increasing levels of thyroid hormone on VWF and FVIII were confirmed in this study.…”

“…These effects of FT 4 on fibrinogen and PAI‐1 were also observed in the study of Horacek et al . . In Fig.…”

Cerebral Venous Thrombosis Associated With Graves Hyperthyroidism

“…Increased thyroid hormones may enhance coagulation factor synthesis or secretion (13), or they may inhibit fibrinolysis. Case reports have described associations of hyperthyroidism with various hypercoagulable conditions, including low levels of protein S (14) or antithrombin III (10,14), and increased levels of fibrinogen (15,16), von Willebrand factor (15,16), factor VIII (15)(16)(17), factor IX (16), and plasminogen activator inhibitor-1 (15,16). Antiphospholipid antibody syndrome, a hypercoagulable condition, has also been associated with hyperthyroidism (18,19).…”

Should We Screen Patients with Unprovoked Venous Thromboembolism for Hyperthyroidism? Report of Several Paradigmatic Clinical Cases from the RIETE Registry

“…Hyperthyroidism, in fact, has been already associated to several abnormalities of coagulation and fi brinolysis [18][19][20][21] with a trend to hypercoagulation thus suggesting a potential role in pathophysiology of VTE.…”