Download PDF
Semin Thromb Hemost 2018; 44(07): 676-682
DOI: 10.1055/s-0038-1666825
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thyroid Disorders and Hemostasis

Laura P.B. Elbers
1   Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, The Netherlands
,
Alessandro Squizzato
2   Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy
,
Victor E.A. Gerdes
1   Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Publication Date:
25 July 2018 (online)

    Permissions and Reprints

Abstract

Lower levels of free thyroxine (whether this is endogenous or exogenous) lead to a hypocoagulable state, and higher levels of free thyroxine lead to a hypercoagulable state. In this narrative review, the effects of different levels of thyroid hormones on clinical end points are described. Hypothyroidism is associated with an increased bleeding risk, whereas hyperthyroidism leads to an increased risk of venous thrombosis. Besides, effects of thyroid hormone on the heart may indirectly influence hemostasis. Hyperthyroidism leads to a higher incidence of atrial fibrillation and atrial flutter, and, at least partly by that mechanism, a higher risk of cerebral arterial thrombosis. In addition, compression effects of goiter on developing venous thrombosis are described. This is caused by local stasis of blood due to tumor expansion.

Keywords

thyroid hormones - coagulation - fibrinolysis - bleeding - venous thrombosis - goiter
 

  • References

  • 1 Doyle JB. Obstruction of the longitudinal sinus. Arch Neurol Psychiatry 1927; 29: 374-382
    PubMedGoogle Scholar
  • 2 Gullu S, Sav H, Kamel N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism. Eur J Endocrinol 2005; 152 (03) 355-361
    CrossrefPubMedGoogle Scholar
  • 3 Yango J, Alexopoulou O, Eeckhoudt S, Hermans C, Daumerie C. Evaluation of the respective influence of thyroid hormones and TSH on blood coagulation parameters after total thyroidectomy. Eur J Endocrinol 2011; 164 (04) 599-603
    CrossrefPubMedGoogle Scholar
  • 4 Myrup B, Bregengård C, Faber J. Primary haemostasis in thyroid disease. J Intern Med 1995; 238 (01) 59-63
    CrossrefPubMedGoogle Scholar
  • 5 Verkleij CJ, Stuijver DJ, van Zaane B. , et al. Thrombin-activatable fibrinolysis inhibitor in hypothyroidism and hyperthyroxinaemia. Thromb Haemost 2013; 109 (02) 214-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Stuijver DJ, van Zaane B, Romualdi E, Brandjes DP, Gerdes VE, Squizzato A. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Thromb Haemost 2012; 108 (06) 1077-1088
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Lippi G, Franchini M, Targher 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 (03) 362-365
    CrossrefPubMedGoogle Scholar
  • 8 Akinci B, Demir T, Comlekci A. , et al. Effect of levothyroxine suppression therapy on plasma thrombin activatable fibrinolysis inhibitor antigen levels in benign thyroid nodules. Med Princ Pract 2011; 20 (01) 23-28
    CrossrefPubMedGoogle Scholar
  • 9 Hooper JM, Stuijver DJ, Orme SM. , et al. Thyroid dysfunction and fibrin network structure: a mechanism for increased thrombotic risk in hyperthyroid individuals. J Clin Endocrinol Metab 2012; 97 (05) 1463-1473
    Google Scholar
  • 10 Debeij J, van Zaane B, Dekkers OM. , et al. High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study. J Thromb Haemost 2014; 12 (06) 839-846
    CrossrefPubMedGoogle Scholar
  • 11 Van Zaane B, Squizzato A, Debeij J. , et al. Alterations in coagulation and fibrinolysis after levothyroxine exposure in healthy volunteers: a controlled randomized crossover study. J Thromb Haemost 2011; 9 (09) 1816-1824
    CrossrefPubMedGoogle Scholar
  • 12 Engelmann B, Bischof J, Dirk AL. , et al. Effect of experimental thyrotoxicosis onto blood coagulation: a proteomics study. Eur Thyroid J 2015; 4 (Suppl. 01) 119-124
    CrossrefPubMedGoogle Scholar
  • 13 Debeij J, Cannegieter SC, VAN Zaane B. , et al. The effect of changes in thyroxine and thyroid-stimulating hormone levels on the coagulation system. J Thromb Haemost 2010; 8 (12) 2823-2826
    CrossrefPubMedGoogle Scholar
  • 14 Horacek J, Maly J, Svilias I. , et al. Prothrombotic changes due to an increase in thyroid hormone levels. Eur J Endocrinol 2015; 172 (05) 537-542
    CrossrefPubMedGoogle Scholar
  • 15 Demir T, Akinci B, Comlekci A. , et al. Levothyroxine (LT4) suppression treatment for benign thyroid nodules alters coagulation. Clin Endocrinol (Oxf) 2009; 71 (03) 446-450
    CrossrefPubMedGoogle Scholar
  • 16 Stuijver DJ, Piantanida E, van Zaane B. , et al. Acquired von Willebrand syndrome in patients with overt hypothyroidism: a prospective cohort study. Haemophilia 2014; 20 (03) 326-332
    CrossrefPubMedGoogle Scholar
  • 17 Manfredi E, van Zaane B, Gerdes VE, Brandjes DP, Squizzato A. Hypothyroidism and acquired von Willebrand's syndrome: a systematic review. Haemophilia 2008; 14 (03) 423-433
    CrossrefPubMedGoogle Scholar
  • 18 Debeij J, Cannegieter SC, van Zaane B. , et al. Major haemorrhage during vitamin K antagonist treatment: the influence of thyroid hormone levels. Eur Thyroid J 2014; 3 (01) 32-37
    CrossrefPubMedGoogle Scholar
  • 19 Elbers LP, Boon HA, Moes MI. , et al. Plasma levels of free thyroxine and risk of major bleeding in bariatric surgery. Eur Thyroid J 2016; 5 (02) 139-144
    CrossrefPubMedGoogle Scholar
  • 20 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353 (9159): 1167-1173
    CrossrefPubMedGoogle Scholar
  • 21 Dekkers OM, Horváth-Puhó E, Cannegieter SC, Vandenbroucke JP, Sørensen HT, Jørgensen JO. Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study. Eur J Endocrinol 2017; 176 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 22 Kootte RS, Stuijver DJ, Dekkers OM. , et al. The incidence of venous thromboembolism in patients with overt hyperthyroidism: a retrospective multicentre cohort study. Thromb Haemost 2012; 107 (03) 417-422
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Kim DD, Chunilal S, Young S, Cutfield R. A study of venous thrombosis incidence in patients with acute hyperthyroidism. Intern Med J 2013; 43 (04) 361-365
    CrossrefPubMedGoogle Scholar
  • 24 Lin HC, Yang LY, Kang JH. Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5-year follow-up study. J Thromb Haemost 2010; 8 (10) 2176-2181
    CrossrefPubMedGoogle Scholar
  • 25 Ramagopalan SV, Wotton CJ, Handel AE, Yeates D, Goldacre MJ. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study. BMC Med 2011; 9: 1
    CrossrefPubMedGoogle Scholar
  • 26 Zöller B, Li X, Sundquist J, Sundquist K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 2012; 379 (9812): 244-249
    CrossrefPubMedGoogle Scholar
  • 27 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. ; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
    CrossrefPubMedGoogle Scholar
  • 28 Debeij J, Dekkers OM, Asvold BO. , et al. Increased levels of free thyroxine and risk of venous thrombosis in a large population-based prospective study. J Thromb Haemost 2012; 10 (08) 1539-1546
    CrossrefPubMedGoogle Scholar
  • 29 van Zaane B, Squizzato A, Huijgen R. , et al. Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. Blood 2010; 115 (22) 4344-4349
    CrossrefPubMedGoogle Scholar
  • 30 Verberne HJ, Fliers E, Prummel MF, Stam J, Brandjes DP, Wiersinga WM. Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis. Thyroid 2000; 10 (07) 607-610
    CrossrefPubMedGoogle Scholar
  • 31 Bensalah M, Squizzato A, Ould Kablia S, Menia H, Kemali Z. Cerebral vein and sinus thrombosis and hyperthyrodism: a case report and a systematic review of the literature. Thromb Res 2011; 128 (01) 98-100
    CrossrefPubMedGoogle Scholar
  • 32 Franchini M, Lippi G, Targher G. Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review. Clin Appl Thromb Hemost 2011; 17 (04) 387-392
    CrossrefPubMedGoogle Scholar
  • 33 Dai A, Wasay M, Dubey N, Giglio P, Bakshi R. Superior sagittal sinus thrombosis secondary to hyperthyroidism. J Stroke Cerebrovasc Dis 2000; 9 (02) 89-90
    CrossrefPubMedGoogle Scholar
  • 34 Mouton S, Nighoghossian N, Berruyer M. , et al. Hyperthyroidism and cerebral venous thrombosis. Eur Neurol 2005; 54 (02) 78-80
    CrossrefPubMedGoogle Scholar
  • 35 Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol 2014; 10 (10) 582-591
    CrossrefPubMedGoogle Scholar
  • 36 Traube E, Coplan NL. Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature. Tex Heart Inst J 2011; 38 (03) 225-228
    PubMedGoogle Scholar
  • 37 Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med 2004; 164 (15) 1675-1678
    CrossrefPubMedGoogle Scholar
  • 38 Selmer C, Olesen JB, Hansen ML. , et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ 2012; 345: e7895
    CrossrefPubMedGoogle Scholar
  • 39 Sheu JJ, Kang JH, Lin HC, Lin HC. Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010; 41 (05) 961-966
    CrossrefPubMedGoogle Scholar
  • 40 Siu CW, Pong V, Zhang X. , et al. Risk of ischemic stroke after new-onset atrial fibrillation in patients with hyperthyroidism. Heart Rhythm 2009; 6 (02) 169-173
    CrossrefPubMedGoogle Scholar
  • 41 Martin SS, Daya N, Lutsey PL. , et al. Thyroid function, cardiovascular risk factors, and incident atherosclerotic cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study. J Clin Endocrinol Metab 2017; 102 (09) 3306-3315
    CrossrefPubMedGoogle Scholar
  • 42 Diao M, Kane A, Diop IB, Sarr M, Ba SA, Diouf SM. Cardiac thyrotoxicosis and left ventricular thrombosis, a case report [in French]. Dakar Méd 1998; 43 (02) 243-244
    PubMedGoogle Scholar
  • 43 Duntas LH, Brenta G. The effect of thyroid disorders on lipid levels and metabolism. Med Clin North Am 2012; 96 (02) 269-281
    CrossrefPubMedGoogle Scholar
  • 44 Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995; 155 (14) 1490-1495
    CrossrefPubMedGoogle Scholar
  • 45 Sjouke B, Langslet G, Ceska R. , et al. Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study. Lancet Diabetes Endocrinol 2014; 2 (06) 455-463
    CrossrefPubMedGoogle Scholar
  • 46 Elbers LP, Kastelein JJ, Sjouke B. Thyroid hormone mimetics: the past, current status and future challenges. Curr Atheroscler Rep 2016; 18 (03) 14
    CrossrefPubMedGoogle Scholar
  • 47 Elbers LP, Moran C, Gerdes VE. , et al. The hypercoagulable state in hyperthyroidism is mediated via the thyroid hormone β receptor pathway. Eur J Endocrinol 2016; EJE-15-1249
    PubMedGoogle Scholar
  • 48 Park HS, Gye HJ, Kim JM, Lee YJ. A patient with branch retinal vein occlusion accompanied by superior ophthalmic vein thrombosis due to severe superior ophthalmic vein enlargement in a patient with graves ophthalmopathy. J Craniofac Surg 2014; 25 (04) e322-e324
    CrossrefPubMedGoogle Scholar
  • 49 Anders HJ. Compression syndromes caused by substernal goitres. Postgrad Med J 1998; 74 (872) 327-329
    CrossrefPubMedGoogle Scholar
  • 50 Aasted A, Bertelsen S. Superior vena caval syndrome in benign mediastinal goitre. Acta Chir Scand 1981; 147 (06) 405-408
    PubMedGoogle Scholar
  • 51 Kucher N. Clinical practice. Deep-vein thrombosis of the upper extremities. N Engl J Med 2011; 364 (09) 861-869
    CrossrefPubMedGoogle Scholar
  • 52 Hyer SL, Dandekar P, Newbold K. , et al. Thyroid cancer causing obstruction of the great veins in the neck. World J Surg Oncol 2008; 6: 36
    CrossrefPubMedGoogle Scholar
  • 53 Tiede DJ, Tefferi A, Kochhar R, Thompson GB, Hay ID. Paraneoplastic cholestasis and hypercoagulability associated with medullary thyroid carcinoma. Resolution with tumor debulking. Cancer 1994; 73 (03) 702-705
    CrossrefPubMedGoogle Scholar
  • 54 Raveh E, Cohen M, Shpitzer T, Feinmesser R. Carcinoma of the thyroid: a cause of hypercoagulability?. Ear Nose Throat J 1995; 74 (02) 110-112
    CrossrefPubMedGoogle Scholar
  • 55 Lal G, Brennan TV, Hambleton J, Clark OH. Coagulopathy, marantic endocarditis, and cerebrovascular accidents as paraneoplastic features in medullary thyroid cancer--case report and review of the literature. Thyroid 2003; 13 (06) 601-605
    CrossrefPubMedGoogle Scholar