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Semin Thromb Hemost 2009; 35(3): 288-294
DOI: 10.1055/s-0029-1222607
© Thieme Medical Publishers

Thyroid Dysfunction and Hemostasis: An Issue Still Unresolved

Massimo Franchini1 , Martina Montagnana2 , Franco Manzato3 , Pier Paolo Vescovi4
  • 1Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
  • 2Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Verona, Italy
  • 3Laboratorio di Patologia Clinica, Ospedale “Carlo Poma,” Mantova, Italy
  • 4Dipartimento di Medicina, Struttura Complessa di Medicina Interna, Ospedale “Carlo Poma,” Mantova, Italy
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Publication History

Publication Date:
18 May 2009 (online)

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ABSTRACT

Thyroid hormones exert various effects on the hemostatic system, as documented by the fact that subclinical or overt thyroid dysfunctions may be associated with hypocoagulable or hypercoagulable states. In this review, the hemostatic balance (primary hemostasis, coagulation factors, and fibrinolytic system) in different thyroid disorders is analyzed from a laboratory, pathogenic, and clinical point of view. Although limited, the published studies suggest that patients with hyperthyroidism or subclinical hypothyroidism have an increased thrombotic risk, whereas patients with overt hypothyroidism have a bleeding tendency. Further trials on larger series of patients are needed to confirm these preliminary findings and to elucidate the pathogenic mechanisms regulating the complex interaction between thyroid disorders and hemostasis.

KEYWORDS

Thyroid - hemostasis - bleeding - thrombosis - hypothyroidism - hyperthyroidism

REFERENCES

  • 1 Squizzato A, Romualdi E, Büller H R, Gerdes V EA. Clinical review: thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review.  J Clin Endocrinol Metab. 2007;  92 2415-2420
    CrossrefPubMedGoogle Scholar
  • 2 Simone J V, Abildgaard C F, Schulman I. Blood coagulation in thyroid dysfunction.  N Engl J Med. 1965;  273 1057-1061
    CrossrefPubMedGoogle Scholar
  • 3 Myrup B, Bregengård C, Faber J. Primary haemostasis in thyroid disease.  J Intern Med. 1995;  238 59-63
    CrossrefPubMedGoogle Scholar
  • 4 Hofbauer L C, Heufelder A E. Coagulation disorders in thyroid diseases.  Eur J Endocrinol. 1997;  136 1-7
    CrossrefPubMedGoogle Scholar
  • 5 Squizzato A, Gerdes V EA, Ageno W, Büller H R. The coagulation system in endocrine disorders: a narrative review.  Intern Emerg Med. 2007;  2 76-83
    CrossrefPubMedGoogle Scholar
  • 6 Franchini M. Hemostasis and thyroid diseases revisited.  J Endocrinol Invest. 2004;  27 886-892
    PubMedGoogle Scholar
  • 7 Marongiu F, Cauli C, Mariotti S. Thyroid, hemostasis and thrombosis.  J Endocrinol Invest. 2004;  27 1065-1071
    PubMedGoogle Scholar
  • 8 Ford H C, Carter J M. Haemostasis in hypothyroidism.  Postgrad Med J. 1990;  66 280-284
    CrossrefPubMedGoogle Scholar
  • 9 Erem C, Kavgaci H, Ersöz H O et al.. Blood coagulation and fibrinolytic activity in hypothyroidism.  Int J Clin Pract. 2003;  57 78-81
    PubMedGoogle Scholar
  • 10 Dalton R G, Dewar M S, Savidge G F et al.. Hypothyroidism as a cause of acquired von Willebrand's disease.  Lancet. 1987;  1 1007-1009
    PubMedGoogle Scholar
  • 11 Thornton J G, Parapia L A, Minford A MB. Hypothyroidism and von Willebrand's disease.  Lancet. 1987;  1 1314-1315
    PubMedGoogle Scholar
  • 12 Nitu-Whalley I C, Lee C A. Acquired von Willebrand syndrome—report of 10 cases and review of the literature.  Haemophilia. 1999;  5 318-326
    CrossrefPubMedGoogle Scholar
  • 13 Michiels J J, 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;  7 113-115
    CrossrefPubMedGoogle Scholar
  • 14 Attivissimo L A, Lichtman S M, Klein I. Acquired von Willebrand's syndrome causing a hemorrhagic diathesis in a patient with hypothyroidism.  Thyroid. 1995;  5 399-401
    CrossrefPubMedGoogle Scholar
  • 15 Blesing N E, Hambley H, McDonald G A. Acquired von Willebrand's disease and hypothyroidism: report of a case presenting with menorrhagia.  Postgrad Med J. 1990;  66 474-476
    CrossrefPubMedGoogle Scholar
  • 16 Bruggers C S, McElligott K, Rallison M L. Acquired von Willebrand disease in twins with autoimmune hypothyroidism: response to desmopressin and L-thyroxine therapy.  J Pediatr. 1994;  125(6 Pt 1) 911-913
    PubMedGoogle Scholar
  • 17 Levesque H, Borg J Y, Cailleux N et al.. Acquired von Willebrand's syndrome associated with decrease of plasminogen activator and its inhibitor during hypothyroidism.  Eur J Med. 1993;  2 287-288
    PubMedGoogle Scholar
  • 18 Aylesworth C A, Smallridge R C, Rick M E, Alving B M. Acquired von Willebrand's disease: a rare manifestation of postpartum thyroiditis.  Am J Hematol. 1995;  50 217-219
    CrossrefPubMedGoogle Scholar
  • 19 Tjan-Heijnen V CG, Harthoorn-Lasthuizen E J, Kurstjens R MA, Koolen M I. A patient with postpartum primary hypothyroidism and acquired von Willebrand's disease.  Neth J Med. 1994;  44 91-94
    PubMedGoogle Scholar
  • 20 Franchini M, de Gironcoli M, Lippi G et al.. Efficacy of desmopressin as surgical prophylaxis in patients with acquired von Willebrand disease undergoing thyroid surgery.  Haemophilia. 2002;  8 142-144
    CrossrefPubMedGoogle Scholar
  • 21 Franchini M, Zugni C, Veneri D et al.. High prevalence of acquired von Willebrand's syndrome in patients with thyroid diseases undergoing thyroid surgery.  Haematologica. 2004;  89 1341-1346
    PubMedGoogle Scholar
  • 22 Franchini M, Veneri D, Lippi G. Analysis of thyroid hormone status in 131 consecutive individuals with low von Willebrand factor levels.  Thromb Haemost. 2005;  93 392-393
    PubMedGoogle Scholar
  • 23 Farid N R, Griffiths B L, Collins J R, Marshall W H, Ingram D W. Blood coagulation and fibrinolysis in thyroid disease.  Thromb Haemost. 1976;  35 415-422
    PubMedGoogle Scholar
  • 24 Marongiu F, Conti M, Murtas M L, Mameli G, Sorano G G, Martino E. Activation of blood coagulation and fibrinolysis in Graves' disease.  Horm Metab Res. 1991;  23 609-611
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Erem C, Ersöz H O, Karti S S et al.. Blood coagulation and fibrinolysis in patients with hyperthyroidism.  J Endocrinol Invest. 2002;  25 345-350
    CrossrefPubMedGoogle Scholar
  • 26 Hymes K, Blum M, Lackner H, Karpatkin S. Easy bruising, thrombocytopenia, and elevated platelet immunoglobulin G in Graves' disease and Hashimoto's thyroiditis.  Ann Intern Med. 1981;  94 27-30
    PubMedGoogle Scholar
  • 27 Lamberg B A, Kivikangas V, Pelkonen R, Vuopio P. Thrombocytopenia and decreased life-span of thrombocytes in hyperthyroidism.  Ann Clin Res. 1971;  3 98-102
    PubMedGoogle Scholar
  • 28 Kurata Y, Nishioeda Y, Tsubakio T, Kitani T. Thrombocytopenia in Graves' disease: effect of T3 on platelet kinetics.  Acta Haematol. 1980;  63 185-190
    CrossrefPubMedGoogle Scholar
  • 29 Panzer S, Haubenstock A, Minar E. Platelets in hyperthyroidism: studies on platelet counts, mean platelet volume, 111-indium-labeled platelet kinetics, and platelet-associated immunoglobulins G and M.  J Clin Endocrinol Metab. 1990;  70 491-496
    CrossrefPubMedGoogle Scholar
  • 30 Marshall J S, Weisberger A S, Levy R P. Coexistent idiopathic thrombocytopenic purpura and hyperthyroidism.  Ann Intern Med. 1967;  67 411-414
    PubMedGoogle Scholar
  • 31 Adrouny A, Sandler R M, Carmel R. Variable presentation of thrombocytopenia in Graves' disease.  Arch Intern Med. 1982;  142 1460-1464
    CrossrefPubMedGoogle Scholar
  • 32 Pinals R S, Tomar R H, Haas D C, Farah R. Graves' disease, myasthenia gravis, and purpura.  Ann Intern Med. 1977;  87 250
    PubMedGoogle Scholar
  • 33 Yamaguchi K, Ookubo Y, Matsuda H, Suzaki K, Fukushima H, Uzawa H. Idiopathic thrombocytopenic purpura subsequent to Graves' disease and insulin-dependent diabetes mellitus.  Diabetes Res Clin Pract. 1987;  3 233-237
    CrossrefPubMedGoogle Scholar
  • 34 Lio S, Albin M, Girelli G et al.. Abnormal thyroid function test results in patients with Fisher-Evans syndrome.  J Endocrinol Invest. 1993;  16 163-167
    PubMedGoogle Scholar
  • 35 Crabtree G R, Lee J C, Cornwell III G G. Letter: autoimmune thrombocytopenia purpura and Hashimoto's thyroiditis.  Ann Intern Med. 1975;  83 371-372
    PubMedGoogle Scholar
  • 36 Ho S L, Shah M, Williams A C. Idiopathic thrombocytopenic purpura and autoimmune thyroiditis in a patient with myasthenia gravis.  Muscle Nerve. 1992;  15 966-967
    PubMedGoogle Scholar
  • 37 Segal B M, Weintraub M I. Hashimoto's thyroiditis, myasthenia gravis, idiopathic thrombocytopenic purpura.  Ann Intern Med. 1976;  85 761-763
    PubMedGoogle Scholar
  • 38 Cordiano I, Betterle C, Spadaccino C A, Soini B, Girolami A, Fabris F. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?.  Clin Exp Immunol. 1998;  113 373-378
    CrossrefPubMedGoogle Scholar
  • 39 Hofbauer L C, Spitzweg C, Schmauss S, Heufelder A E. Graves disease associated with autoimmune thrombocytopenic purpura.  Arch Intern Med. 1997;  157 1033-1036
    CrossrefPubMedGoogle Scholar
  • 40 Zeigler Z R, Hasiba U, Lewis J H, Vagnucci A H, West V A, Bezek E A. Hemostatic defects in response to aspirin challenge in hypothyroidism.  Am J Hematol. 1986;  23 391-399
    CrossrefPubMedGoogle Scholar
  • 41 Hellem A J, Segaard E, Solem J H. The adhesiveness of human blood platelets and thyroid function.  Acta Med Scand. 1975;  197 15-17
    PubMedGoogle Scholar
  • 42 Edson J R, Fecher D R, Doe R P. Low platelet adhesiveness and other hemostatic abnormalities in hypothyroidism.  Ann Intern Med. 1975;  82 342-346
    PubMedGoogle Scholar
  • 43 Palareti G, Biagi G, Legnani C et al.. Association of reduced factor VIII with impaired platelet reactivity to adrenalin and collagen after total thyroidectomy.  Thromb Haemost. 1989;  62 1053-1056
    PubMedGoogle Scholar
  • 44 Egeberg B O. Influence of thyroid function on the blood clotting system.  Scand J Clin Lab Invest. 1963;  15 1-7
    CrossrefPubMedGoogle Scholar
  • 45 Rogers II J S, Shane S R, Jencks F S. Factor VIII activity and thyroid function.  Ann Intern Med. 1982;  97 713-716
    PubMedGoogle Scholar
  • 46 Rogers II J S, Shane S R. Factor VIII activity in normal volunteers receiving oral thyroid hormone.  J Lab Clin Med. 1983;  102 444-449
    PubMedGoogle Scholar
  • 47 Nordoy A, Vik-Mo H, Berntsen H. Haemostatic and lipid abnormalities in hypothyroidism.  Scand J Haematol. 1976;  16 154-160
    CrossrefPubMedGoogle Scholar
  • 48 Gullu S, Sav H, Kamel N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism.  Eur J Endocrinol. 2005;  152 355-361
    CrossrefPubMedGoogle Scholar
  • 49 Meiklejohn D J, Watson H G. Acquired haemophilia in association with organ-specific autoimmune disease.  Haemophilia. 2001;  7 523-525
    CrossrefPubMedGoogle Scholar
  • 50 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;  25 246-249
    PubMedGoogle Scholar
  • 51 Sievert R, Goldstein M L, Surks M I. Graves' disease and autoimmune factor VIII deficiency.  Thyroid. 1996;  6 245-247
    PubMedGoogle Scholar
  • 52 Chadarevian R, Bruckert E, Ankri A, Beucler I, Giral P, Turpin G. Relationship between thyroid hormones and plasma D-dimer levels.  Thromb Haemost. 1998;  79 99-103
    PubMedGoogle Scholar
  • 53 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;  86 732-737
    CrossrefPubMedGoogle Scholar
  • 54 Müller B, Tsakiris D A, Roth C B, Guglielmetti M, Staub J J, Marbet G A. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease.  Eur J Clin Invest. 2001;  31 131-137
    CrossrefPubMedGoogle Scholar
  • 55 Marongiu F, Biondi G, Conti M et al.. Is a hypercoagulable state present in hypothyroidism?.  Thromb Haemost. 1992;  67 729
    PubMedGoogle Scholar
  • 56 Homoncik M, Gessl A, Ferlitsch A, Jilma B, Vierhapper H. Altered platelet plug formation in hyperthyroidism and hypothyroidism.  J Clin Endocrinol Metab. 2007;  92 3006-3012
    CrossrefPubMedGoogle Scholar
  • 57 Burggraaf J, Lalezari S, Emeis J J et al.. Endothelial function in patients with hyperthyroidism before and after treatment with propranolol and thiamazol.  Thyroid. 2001;  11 153-160
    CrossrefPubMedGoogle Scholar
  • 58 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;  76 609-614
    CrossrefPubMedGoogle Scholar
  • 59 Hak A E, Pols H A, Visser T J, Drexhage H A, Hofman A, Witteman J C. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.  Ann Intern Med. 2000;  132 270-278
    PubMedGoogle Scholar
  • 60 Özcan M A, Cömlekçi A, Demirkan F et al.. Plasma levels of free tissue factor pathway inhibitor in patients with various thyroid disorders.  Thromb Res. 2003;  110 243-247
    CrossrefPubMedGoogle Scholar
  • 61 Loeliger E A, Esch B. The biological disappearance rate of prothrombin, factors VII, IX and X from plasma in hypothyroidism, hyperthyroidism and during fever.  Thromb Diath Haemorrh. 1964;  10 267-277
    PubMedGoogle Scholar
  • 62 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. 2008;  , September 12 (Epub ahead of print)
    PubMedGoogle Scholar
  • 63 Erem C. Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.  Clin Endocrinol (Oxf). 2006;  64 323-329
    CrossrefPubMedGoogle Scholar
  • 64 Cantürk Z, Cetinarslan B, Tarkun I, Cantürk N Z, Ozden M, Duman C. Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism.  Thyroid. 2003;  13 971-977
    CrossrefPubMedGoogle Scholar
  • 65 Li Y, Chen H, Tan J, Wang X, Liang H, Sun X. Impaired release of tissue plasminogen activator from the endothelium in Graves' disease - indicator of endothelial dysfunction and reduced fibrinolytic capacity.  Eur J Clin Invest. 1998;  28 1050-1054
    CrossrefPubMedGoogle Scholar
  • 66 Morishita E, Hashimoto T, Asakura H et al.. Increased plasma levels of free tissue factor pathway inhibitor in patients with Graves' disease.  Thromb Haemost. 1998;  79 919-923
    PubMedGoogle Scholar
  • 67 Chadarevian R, Bruckert E, Giral P, Turpin G. Relationship between thyroid hormones and fibrinogen levels.  Blood Coagul Fibrinolysis. 1999;  10 481-486
    PubMedGoogle Scholar
  • 68 Grant P J, Medcalf R L. Hormonal regulation of haemostasis and the molecular biology of the fibrinolytic system.  Clin Sci (Lond). 1990;  78 3-11
    PubMedGoogle Scholar
  • 69 Marongiu F, Conti M, Mameli G et al.. Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.  J Endocrinol Invest. 1988;  11 723-725
    PubMedGoogle Scholar
  • 70 Polikar R, Burger A G, Scherrer U S, Nicod P. The thyroid and the heart.  Circulation. 1993;  87 1435-1441
    CrossrefPubMedGoogle Scholar
  • 71 Woeber K A. Thyrotoxicosis and the heart.  N Engl J Med. 1992;  327 94-98
    CrossrefPubMedGoogle Scholar
  • 72 Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease.  Endocrine. 2004;  24 1-13
    CrossrefPubMedGoogle Scholar
  • 73 Mariotti S, Cambuli V M. Cardiovascular risk in elderly hypothyroid patients.  Thyroid. 2007;  17 1067-1073
    CrossrefPubMedGoogle Scholar
  • 74 Duntas L H, Wartofsky L. Cardiovascular risk and subclinical hypothyroidism: focus on lipids and new emerging risk factors. What is the evidence?.  Thyroid. 2007;  17 1075-1084
    CrossrefPubMedGoogle Scholar
  • 75 Singh S, Duggal J, Molnar J, Maldonado F, Barsano C P, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis.  Int J Cardiol. 2008;  125 41-48
    CrossrefPubMedGoogle Scholar
  • 76 Ochs N, Auer R, Bauer D C et al.. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality.  Ann Intern Med. 2008;  148 832-845
    CrossrefPubMedGoogle Scholar

Dr. Massimo FranchiniM.D. 

Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio

Azienda Ospedaliero-Universitaria di Parma, Via Gramsci, 14; 37124, Parma; Italy

Email: massimo.franchini@azosp.vr.it