The Spectrum of Coagulation Abnormalities in Thyroid Disorders

Pier Paolo Vescovi; Emmanuel J Favaloro; Giuseppe Lippi; Massimo Garofano; Martina Montagnana; Franco Manzato; Massimo Franchini

doi:10.1055/s-0030-1270065

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2011; 37(1): 007-010
DOI: 10.1055/s-0030-1270065

The Spectrum of Coagulation Abnormalities in Thyroid Disorders

Pier Paolo Vescovi¹ , Emmanuel J. Favaloro² , Giuseppe Lippi³ , Massimo Garofano¹ , Martina Montagnana⁴ , Franco Manzato⁵ , Massimo Franchini⁶

¹Divisione di Medicina, Ospedale “Carlo Poma,” Mantova, Italy
²Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, Australia
³Unità Operativa di Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
⁴Istituto di Chimica e Microscopia Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Verona, Italy
⁵Laboratorio di Analisi Chimico-Cliniche, Ospedale “Carlo Poma,” Mantova, Italy
⁶Servizio di Immuno-ematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma; Italy

Abstract

ABSTRACT

The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors including hormones. A variety of endocrine disorders have been reported to be associated with coagulation abnormalities, ranging from mild laboratory changes to clinically relevant thrombotic or bleeding manifestations. In this review, we summarize the current knowledge on the main abnormalities of the coagulation and fibrinolytic systems associated with thyroid dysfunctions. Overall, although mostly based on uncontrolled studies, data in the literature suggest that patients with hyperthyroidism or subclinical hypothyroidism have a hypercoagulative state, whereas patients with overt hypothyroidism have a bleeding tendency.

KEYWORDS

Bleeding - thrombosis - hyperthyroidism - hypothyroidism

Full Text

References

REFERENCES

1 Franchini M, Lippi G, Manzato F, Vescovi P P, Targher G. Hemostatic abnormalities in endocrine and metabolic disorders. Eur J Endocrinol. 2010; 162 (3) 439-451
2 Squizzato A, Gerdes V EA, Ageno W, Büller H R. The coagulation system in endocrine disorders: a narrative review. Intern Emerg Med. 2007; 2 (2) 76-83
3 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 (7) 2415-2420
4 Franchini M. Hemostasis and thyroid diseases revisited. J Endocrinol Invest. 2004; 27 (9) 886-892
5 Franchini M, Montagnana M, Manzato F, Vescovi P P. Thyroid dysfunction and hemostasis: an issue still unresolved. Semin Thromb Hemost. 2009; 35 (3) 288-294
6 Mina A, Favaloro E J, Koutts J. Hemostatic dysfunction associated with endocrine disorders as a major risk factor and cause of human morbidity and mortality: a comprehensive meta-review. Semin Thromb Hemost. 2007; 33 (8) 798-809
7 Marongiu F, Barcellona D, Mameli A, Mariotti S. Thyroid disorders and hypocoagulability. Semin Thromb Hemost. 2011; 37 (1) 11-16
8 Erem C. Thyroid disorders and hypercoagulability. Semin Thromb Hemost. 2011; 37 (1) 17-26
9 Erem C. Coagulation and fibrinolysis in thyroid dysfunction. Endocrine. 2009; 36 (1) 110-118
10 Ford H C, Carter J M. Haemostasis in hypothyroidism. Postgrad Med J. 1990; 66 (774) 280-284
11 Erem C, Kavgaci H, Ersöz H O et al.. Blood coagulation and fibrinolytic activity in hypothyroidism. Int J Clin Pract. 2003; 57 (2) 78-81
12 Hofbauer L C, Heufelder A E. Coagulation disorders in thyroid diseases. Eur J Endocrinol. 1997; 136 (1) 1-7
13 Marongiu F, Cauli C, Mariotti S. Thyroid, hemostasis and thrombosis. J Endocrinol Invest. 2004; 27 (11) 1065-1071
14 Dalton R G, Dewar M S, Savidge G F et al. Hypothyroidism as a cause of acquired von Willebrand's disease. Lancet. 1987; 1 (8540) 1007-1009
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 (776) 474-476
16 Thornton J G, Parapia L A, Minford A MB. Hypothyroidism and von Willebrand's disease. Lancet. 1987; 1 (8545) 1314-1315
17 Nitu-Whalley I C, Lee C A. Acquired von Willebrand syndrome—report of 10 cases and review of the literature. Haemophilia. 1999; 5 (5) 318-326
18 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 (2) 113-115
19 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 (5) 399-401
20 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 (3) 91-94
21 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 (2) 142-144
22 Manfredi E, van Zaane B, Gerdes V E, Brandjes D P, Squizzato A. Hypothyroidism and acquired von Willebrand's syndrome: a systematic review. Haemophilia. 2008; 14 (3) 423-433
23 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 (11) 1341-1346
24 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 (4) 1053-1056
25 Myrup B, Bregengård C, Faber J. Primary haemostasis in thyroid disease. J Intern Med. 1995; 238 (1) 59-63
26 Egeberg B O. Influence of thyroid function on the blood clotting system. Scand J Clin Lab Invest. 1963; 15 1-7
27 Rogers II J S, Shane S R, Jencks F S. Factor VIII activity and thyroid function. Ann Intern Med. 1982; 97 (5) 713-716
28 Gullu S, Sav H, Kamel N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism. Eur J Endocrinol. 2005; 152 (3) 355-361
29 Meiklejohn D J, Watson H G. Acquired haemophilia in association with organ-specific autoimmune disease. Haemophilia. 2001; 7 (5) 523-525
30 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 (2) 732-737
31 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 (10) 971-977
32 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 (4) 243-247
33 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 (11) 832-845
34 Duntas L, Biondi B. New insights into subclinical hypothyroidism and cardiovascular risk. Semin Thromb Hemost. 2011; 37 (1) 27-34
35 Hofbauer L C, Spitzweg C, Schmauss S, Heufelder A E. Graves' disease associated with autoimmune thrombocytopenic purpura. Arch Intern Med. 1997; 157 (9) 1033-1036
36 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 (3) 373-378
37 Franchini M, Lippi G, Manzato F, Vescovi P P. Thyroid-associated autoimmune coagulation disorders. J Thromb Thrombolysis. 2010; 29 (1) 87-91
38 Marongiu F, Conti M, Murtas M L et al. Anticardiolipin antibodies in Graves' disease: relationship with thrombin activity in vivo. Thromb Res. 1991; 64 (6) 745-749
39 Hofbauer L C, Spitzweg C, Heufelder A E. Graves' disease associated with the primary antiphospholipid syndrome. J Rheumatol. 1996; 23 (8) 1435-1437
40 Homoncik M, Gessl A, Ferlitsch A, Jilma B, Vierhapper H. Altered platelet plug formation in hyperthyroidism and hypothyroidism. J Clin Endocrinol Metab. 2007; 92 (8) 3006-3012
41 Rogers II J S, Shane S R. Factor VIII activity in normal volunteers receiving oral thyroid hormone. J Lab Clin Med. 1983; 102 (3) 444-449
42 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 (3) 362-365
43 Franchini M, Lippi G, Targher G. Hyperthyroidism and venous thrombosis: a causal or casual association? A systematic literature review. Clin Appl Thromb Hemost. 2010; March 22 (Epub ahead of print)
44 Erem C, Ersöz H O, Karti S S et al. Blood coagulation and fibrinolysis in patients with hyperthyroidism. J Endocrinol Invest. 2002; 25 (4) 345-350
45 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 (5) 919-923
46 Erem C, Ucuncu O, Yilmaz M, Kocak M, Nuhoglu I, Ersoz H O. Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism. Endocrine. 2009; 36 (3) 473-478

Massimo FranchiniM.D.

Servizio di Immunoematologia e Trasfusione

Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

Email: mfranchini@ao.pr.it