Skip to main content
SpringerLink
Log in

Thyroid, hemostasis and thrombosis

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The aim of this paper is to briefly review some practical aspects of the relationship between thyroid function and several disorders of the hemostatic system in terms of bleeding and thrombosis. Thrombocytopenia, acquired hemophilia, hypercoagulability, cardioembolism and other biochemical coagulative and fibrinolytic abnormalities have been described in the past years both in hyper- and hypothyroidism. Since most of hyper- and hypothyroid conditions are the consequence of autoimmune thyroid disease (1), either deranged immune function, altered circulating thyroid hormone concentration, or both may concur in the pathogenesis of hemostatic disorders of potential crucial clinical impact. These aspects will be outlined and discussed in an attempt to give answers to some questions, often arising in the clinical approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mariotti S, Pinna G. Autoimmune thyroid disease. In: Bravermam L ed. Diseases of the thyroid. Totowa: Humana Press. 2003, 107–60.

    Google Scholar 

  2. Marongiu F, Conti M, Murtas ML, Mameli G, Sorano GG, Martino E. What causes the increase in platelet mean volume in thyroid pathological conditions? Thromb Haemost 1990, 63: 323–4.

    PubMed  CAS  Google Scholar 

  3. Ford HC, Toomath RJ, Carter JM, Delahunt JW, Fagerstrom JN. Mean platelet volume is increased in hyperthyroidism. Am J Hematol 1988, 27: 190–3.

    Article  PubMed  CAS  Google Scholar 

  4. Panzer S, Haubenstock A, Minar E. Platelets in hyperthyroidism: studies on platelet counts, mean platelet volume, 111-indiumlabeled platelet kinetics, and platelet-associated immunoglobulins G and M. J Clin Endocrinol Metab 1990, 70: 491–6.

    Article  PubMed  CAS  Google Scholar 

  5. Stiegler G, Stohlawetz P, Brugger S, et al. Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis. Br J Haematol 1998, 101: 656–8.

    Article  PubMed  CAS  Google Scholar 

  6. Ford HC, Carter JM. Haemostasis in hypothyroidism. Postgrad Med J 1990, 66: 280–4.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Myrup B, Bregengard C, Faber J. Primary haemostasis in thyroid disease. J Intern Med 1995, 238: 59–63.

    Article  PubMed  CAS  Google Scholar 

  8. Michiels JJ, Schroyens W, Berneman Z, van der Planken M. Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after treatment with thyroxine. Clin Appl Thromb Hemost 2001, 7: 113–5.

    Article  PubMed  CAS  Google Scholar 

  9. Chadarevian R, Bruckert E, Leenhardt L, Giral P, Ankri A, Turpin G. Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism. J Clin Endocrinol Metab 2001, 86: 732–7.

    Article  PubMed  CAS  Google Scholar 

  10. Jenkins RC, Weetman AP. Disease associations with autoimmune thyroid disease. Thyroid 2002, 12: 977–88.

    Article  PubMed  Google Scholar 

  11. Hofbauer LC, Spitzweg C, Schmauss S, Heufelder AE. Graves disease associated with autoimmune thrombocytopenic purpura. Arch Intern Med 1997, 157: 1033–6.

    Article  PubMed  CAS  Google Scholar 

  12. Bizzaro N. Familial association of autoimmune thrombocytopenia and hyperthyroidism. Am J Hematol 1992, 39: 294–8.

    Article  PubMed  CAS  Google Scholar 

  13. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002, 346: 995–1008.

    Article  PubMed  Google Scholar 

  14. Hofbauer LC, Heufelder AE. Coagulation disorders in thyroid diseases. Eur J Endocrinol 1997, 136: 1–7.

    Article  PubMed  CAS  Google Scholar 

  15. Marongiu F, Cauli C, Mameli G, Usai B, Mariotti S. Apathetic Graves’ disease and acquired hemophilia due to factor VIIIc antibody. J Endocrinol Invest 2002, 25: 246–9.

    Article  PubMed  CAS  Google Scholar 

  16. Sievert R, Goldstein ML, Surks MI. Graves’ disease and autoimmune factor VIII deficiency. Thyroid 1996, 6: 245–7.

    PubMed  CAS  Google Scholar 

  17. Marongiu F, Conti M, Mameli G, et al. Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. J Endocrinol Invest 1988, 11: 723–5.

    Article  PubMed  CAS  Google Scholar 

  18. Erem C, Ersoz HÖ, Karti SS, et al. Blood coagulation and fibrinolysis in patients with hyperthyroidism. J Endocrinol Invest 2002, 25: 345–50.

    Article  PubMed  CAS  Google Scholar 

  19. Rogers JS, Shane SR, Jencks FS. Factor VIII activity and thyroid function. Ann Intern Med 1982, 97: 713–6.

    Article  PubMed  Google Scholar 

  20. Rogers JS, Shane SR. Factor VIII activity in normal volunteers receiving oral thyroid hormone. J Lab Clin Med 1983, 102: 444–9.

    PubMed  CAS  Google Scholar 

  21. Hiller E, Roth W, Wahl R, Kallee E. Thromboplastin activity of extracts of human thyroid glands. Klin Wochenschr 1978, 53: 283–4.

    Article  PubMed  CAS  Google Scholar 

  22. Marongiu F, Conti M, Murtas ML, Mameli G, Sorano GG, Martino E. Activation of blood coagulation and fibrinolysis in Graves’ disease. Horm Metab Res 1991, 23: 609–11.

    Article  PubMed  CAS  Google Scholar 

  23. Matucci-Cerinic M, Valentini G, Sorano GG, et al. Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum 2003, 32: 285–95.

    Article  CAS  Google Scholar 

  24. Esmon CT, Esmon NL, Harris KW. Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J Biol Chem 1982, 257: 7944–7.

    PubMed  CAS  Google Scholar 

  25. de Groot PG. The role of von Willebrand factor in platelet function. Semin Thromb Hemost 2002, 28: 133–8.

    Article  PubMed  Google Scholar 

  26. Morikawa Y, Morikawa A, Makino I. Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves’ disease: TM, a possible new marker of the peripheral activity of thyroid hormones. J Clin Endocrinol Metab 1993, 76: 609–14.

    PubMed  CAS  Google Scholar 

  27. Burggraaf J, Lalezari S, Emeis JJ, et al. Endothelial function in patients with hyperthyroidism before and after treatment with propranolol and thiamazol. Thyroid 2001, 11: 153–60.

    Article  PubMed  CAS  Google Scholar 

  28. Marongiu F, Conti M, Murtas ML, et al. Anticardiolipin antibodies in Graves’ disease: relantionship with thrombin activity in vivo. Thromb Res 1991, 64: 745–9.

    Article  PubMed  CAS  Google Scholar 

  29. Paggi A, Caccavo D, Ferri GM, et al. Anti-cardiolipin antibodies in autoimmune thyroid diseases. Clin Endocrinol 1994, 40: 329–33.

    Article  CAS  Google Scholar 

  30. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002, 346: 752–63.

    Article  PubMed  CAS  Google Scholar 

  31. Takahashi A, Tamura A, Ishikawa O. Antiphospholipid antibody syndrome complicated by Grave’s disease. J Dermatol 2002, 29: 776–80.

    PubMed  Google Scholar 

  32. Hofbauer LC, Spitzweg C, Heufelder AE. Graves’ disease associated with the primary antiphospholipid syndrome. J Rheumatol 1996, 23: 1435–7.

    PubMed  CAS  Google Scholar 

  33. Brandt JT, Barna LK, Triplett DA. Laboratory identification of lupus anticoagulants: results of the Second International Workshop for Identification of Lupus Anticoagulants. On behalf of the Subcommittee on Lupus Anticoagulants/Antiphospholipid Antibodies of the ISTH. Thromb Haemost 1995, 74: 1597–603.

    PubMed  CAS  Google Scholar 

  34. Siegert CE, Smelt AH, de Bruin TW. Superior sagittal sinus thrombosis and thyrotoxicosis. Stroke 1995, 26: 496–7.

    Article  PubMed  CAS  Google Scholar 

  35. Dulli DA, Luzzio CC, Williams EC, Schutta HS. Cerebral venous thrombosis and activated protein C resistance. Stroke 1996, 27: 1731–3.

    Article  PubMed  CAS  Google Scholar 

  36. Schutta HS, Williams EC, Baranski BG, Sutula TP. Cerebral venous thrombosis with plasminogen deficiency. Stroke 1991, 22: 401–5.

    Article  PubMed  CAS  Google Scholar 

  37. Verberne HJ, Fliers E, Prummel MF, Stam J, Brandjes DP, Wiersinga WM. Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis. Thyroid 2000, 10: 607–10.

    Article  PubMed  CAS  Google Scholar 

  38. Page SR, Scott AR. Thyroid storm in a young woman resulting in bilateral basal ganglia infarction. Postgrad Med J 1993, 69: 813–5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001, 344: 501–9.

    Article  PubMed  CAS  Google Scholar 

  40. Nordyke RA, Gilbert FI Jr, Harada ASM. Graves’ disease. Influence of age on clinical findings. Arch Intern Med 1988, 148: 626–31.

    Article  PubMed  CAS  Google Scholar 

  41. Shimizu T, Koide S, Noh JY, Sugino K, Ito K, Nakazawa H. Hyperthyroidism and the management of atrial fibrillation. Thyroid 2002, 12: 489–93.

    Article  PubMed  Google Scholar 

  42. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994, 331: 1249–52.

    Article  PubMed  CAS  Google Scholar 

  43. Sawin CT. Subclinical hyperthyroidism and atrial fibrillation. Thyroid 2002, 12: 501–3.

    Article  PubMed  Google Scholar 

  44. Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001, 358: 861–5.

    Article  PubMed  CAS  Google Scholar 

  45. Auer J, Scheibner P, Mische T, Langsteger W, Eber O, Eber B. Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 2001, 142: 838–42.

    Article  PubMed  CAS  Google Scholar 

  46. Forfar JC, Miller HC, Toft AD. Occult thyrotoxicosis: a correctable cause of “idiopathic” atrial fibrillation. Am J Cardiol 1979, 44: 9–12.

    Article  PubMed  CAS  Google Scholar 

  47. Osman F, Gammage MD, Sheppard MC, Franklyn JA. Clinical review 142: cardiac dysrhythmias and thyroid dysfunction: the hidden menace? J Clin Endocrinol Metab 2002, 87: 963–7.

    Article  PubMed  CAS  Google Scholar 

  48. Staffurth JS, Gibberd MC, Fui SN. Arterial embolism in thyrotoxicosis with atrial fibrillation. Br Med J 1977, 2: 688–90.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Yuen RW, Gutteridge DH, Thompson PL, Robinson JS. Embolism in thyrotoxic atrial fibrillation. Med J Aust 1979, 1: 630–1.

    PubMed  CAS  Google Scholar 

  50. Hurley DM, Hunter AN, Hewett MJ, Stockigt JR. Atrial fibrillation and arterial embolism in hyperthyroidism. Aust N Z J Med 1981, 11: 391–3.

    Article  PubMed  CAS  Google Scholar 

  51. Bar-Sela S, Ehrenfeld M, Eliakim M. Arterial embolism in thyrotoxicosis with atrial fibrillation. Arch Intern Med 1981, 141: 1191–2.

    Article  PubMed  CAS  Google Scholar 

  52. Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988, 19: 15–8.

    Article  PubMed  CAS  Google Scholar 

  53. Lip GYH, Lowe GDO. ABC of atrial fibrillation: antithrombotic treatment for atrial fibrillation. BMJ 1996, 312: 45–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. A guide to oral anticoagulant treatment. Recommendations of the Italian Federation of Anticoagulation Clinics (FCSA). Haematologica 2003, 88 (Suppl 2): 1–52.

  55. Albers GW, Dalen JE, Laupacis A, Manning WJ, Petersen P, Singer DE. Antithrombotic therapy in atrial fibrillation. Chest 2001, 119: 194S–206S.

    Article  PubMed  CAS  Google Scholar 

  56. Nakazawa HK, Sakurai K, Hamada N, Nomotani N, Ito K. Management of atrial fibrillation in the post-thyrotoxic state. Am J Med 1982, 72: 903–6.

    Article  PubMed  CAS  Google Scholar 

  57. Kamp O, Verhorst PMJ, Visser CA. Transesophageal echocardiography for early cardioversion of atrial fibrillation. Am J Cardiol 2000, 86 (Suppl): 46G–50G.

    Article  PubMed  CAS  Google Scholar 

  58. Palareti G, Leali N, Cocchieri S, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996, 348: 423–8.

    Article  PubMed  CAS  Google Scholar 

  59. Palareti G, Hirsh J, Legnani C, et al. Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study. Arch Intern Med 2000, 160: 470–8.

    Article  PubMed  CAS  Google Scholar 

  60. Barcellona D, Vannini ML, Fenu L, Balestrieri C, Marongiu F. Warfarin or acenocoumarol: which is better in the management of oral anticoagulants? Thromb Haemost 1998, 80: 899–902.

    PubMed  CAS  Google Scholar 

  61. Marongiu F, Sorano GG, Conti M, et al. Known vitamin K intake and management of poorly controlled oral anticoagulant therapy. Lancet 1992, 340: 545–6.

    Article  PubMed  CAS  Google Scholar 

  62. Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of warfarin with drugs and food. Ann Intern Med 1994, 121: 676–83.

    Article  PubMed  CAS  Google Scholar 

  63. Manotti C, Quintavalla R, Pattaccini C, Pini M. Seasonal variation of oral anticoagulant effect. Thromb Haemost 1994, 71: 802–3.

    PubMed  CAS  Google Scholar 

  64. Cortellazzo S, Finazzi G, Viero P, et al. Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. Thromb Haemost 1993, 69: 316–20.

    Google Scholar 

  65. Barcellona D, Contu P, Marongiu F. Patient education and oral anticoagulant therapy. Haematologica 2002, 87: 1081–6.

    PubMed  Google Scholar 

  66. Barcellona D, Contu P, Sorano GG, Pengo V, Marongiu F. The management of oral anticoagulant therapy: the patient’s point of view. Thromb Haemost 2000, 83: 49–53.

    PubMed  CAS  Google Scholar 

  67. Kellett HA, Sawers JS, Boulton FE, Cholerton S, Park BK, Toft AD. Problems of anticoagulation with warfarin in hyperthyroidism. Q J Med 1986, 58: 43–51.

    PubMed  CAS  Google Scholar 

  68. Self TH, Straughn AB, Weisburst MR. Effect of hyperthyroidism on hypoprothrombinemic response to warfarin. Am J Hosp Pharm 1976, 33: 387–9.

    PubMed  CAS  Google Scholar 

  69. Marongiu F, Biondi G, Conti M, et al. Is a hypercoagulable state present in hypothyroidism? Thromb Haemost 1992, 67: 729.

    PubMed  CAS  Google Scholar 

  70. Muller B, Tsakiris DA, Roth CB, Guglielmetti M, Staub JJ, Marbet GA. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur J Clin Invest 2001, 31: 131–7.

    Article  PubMed  CAS  Google Scholar 

  71. Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid 1999, 9: 1163–6.

    Article  PubMed  CAS  Google Scholar 

  72. Hussein WI, Green R, Jacobsen DW, Faiman C. Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism. Ann Intern Med 1999, 131: 348–51.

    Article  PubMed  CAS  Google Scholar 

  73. Nedrebo BG, Ericsson UB, Nygard O, et al. Plasma total homocysteine levels in hyperthyroid and hypothyroid patients. Metabolism 1998, 47: 89–93.

    Article  PubMed  CAS  Google Scholar 

  74. Tawakol A, Forgione MA, Stuehlinger M, et al. Homocysteine impairs coronary microvascular dilator function in humans. J Am Coll Cardiol 2002, 40: 1051–8.

    Article  PubMed  CAS  Google Scholar 

  75. Becker C. Hypothyroidism and atherosclerotic heart disease: pathogenesis, medical management, and the role of coronary artery bypass surgery. Endocr Rev 1985, 6: 432–40.

    Article  PubMed  CAS  Google Scholar 

  76. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 2000, 10: 665–79.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Policlinico Universitario di Monserrato, University of Cagliari, Cagliari, Italy, SS 554

    F. Marongiu MD (Chair of Internal Medicine), C. Cauli (Chair of Internal Medicine) & S. Mariotti (Chair of Endocrinology)

Authors
  1. F. Marongiu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Cauli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Mariotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Marongiu MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marongiu, F., Cauli, C. & Mariotti, S. Thyroid, hemostasis and thrombosis. J Endocrinol Invest 27, 1065–1071 (2004). https://doi.org/10.1007/BF03345311

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345311

Key-words

Search

Navigation