ABSTRACT
This review focuses attention on some practical aspects of the relationship between thyroid disorders and hypocoagulability, as related to an impairment of hemostasis and fibrinolysis. An understanding of this topic in daily clinical practice is important given that the interaction between hemostatic abnormalities and thyroid disorders is still poorly recognized by the medical community. Even if the bleeding tendency is in general mild and may be reversed by restoration of an euthyroid state, severe hemorrhagic events may complicate the course of both hyper- and hypothyroidism, as precipitated by such conditions as thrombocytopenia, acquired von Willebrand syndrome, and acquired hemophilia. The pathogenesis of the hemostatic abnormalities resides in either the direct effect of thyroid hormones or some conditions in an autoimmune mechanism. Physicians and endocrinologists should pay close attention to both clinical hemorrhagic events in their patients as well as to any laboratory abnormalities identified by blood coagulation testing.
KEYWORDS
Hyperthyroidism - hypothyroidism - acquired von Willebrand syndrome - acquired hemophilia - immune thrombocytopenic purpura - fibrinolysis
REFERENCES
-
1
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
-
2
Squizzato A, Romualdi E, Büller H R, Gerdes V E.
Clinical review: thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review.
J Clin Endocrinol Metab.
2007;
92
(7)
2415-2420
-
3
Marongiu F, Cauli C, Mariotti S.
Thyroid, hemostasis and thrombosis.
J Endocrinol Invest.
2004;
27
(11)
1065-1071
-
4
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
(2)
491-496
-
5
Marongiu F, Conti M, Murtas M L, Mameli G, Sorano G G, Martino E.
What causes the increase in platelet mean volume in thyroid pathological conditions?.
Thromb Haemost.
1990;
63
(2)
323-324
-
6
Mousa S S, Davis F B, Davis P J et al..
Human platelet aggregation and degranulation is induced in vitro by L-thyroxine, but not by 3,5,3′-triiodo-L-thyronine or diiodothyropropionic acid (DITPA).
Clin Appl Thromb Hemost.
2010;
16
(3)
288-293
-
7
Kurata Y, Nishioeda Y, Tsubakio T, Kitani T.
Thrombocytopenia in Graves' disease: effect of T3 on platelet kinetics.
Acta Haematol.
1980;
63
(4)
185-190
-
8
Marshall J S, Weisberger A S, Levy R P.
Coexistent idiopathic thrombocytopenic purpura and hyperthyroidism.
Ann Intern Med.
1967;
67
411-414
-
9
Crabtree G R, Lee J C, Cornwell III G G.
Letter: Autoimmune thrombocytopenia purpura and Hashimoto's thyroiditis.
Ann Intern Med.
1975;
83
(3)
371-372
-
10
Bizzaro N.
Familial association of autoimmune thrombocytopenia and hyperthyroidism.
Am J Hematol.
1992;
39
(4)
294-298
-
11
Cines D B, Blanchette V S.
Immune thrombocytopenic purpura.
N Engl J Med.
2002;
346
(13)
995-1008
-
12
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
-
13
Boruchov A M.
Thrombocytopenia in myelodysplastic syndromes and myelofibrosis.
Semin Hematol.
2009;
46
(1, Suppl 2)
S37-S43
-
14
Alter B P.
Diagnosis, genetics, and management of inherited bone marrow failure syndromes.
Hematology Am Soc Hematol Educ Program.
2007;
29-39
-
15
Hofbauer L C, Heufelder A E.
Coagulation disorders in thyroid diseases.
Eur J Endocrinol.
1997;
136
(1)
1-7
-
16
Bartalena L, Bogazzi F, Martino E.
Adverse effects of thyroid hormone preparations and antithyroid drugs.
Drug Saf.
1996;
15
(1)
53-63
-
17
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
(4)
391-399
-
18
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
-
19
Hellem A J, Segaard E, Solem J H.
The adhesiveness of human blood platelets and thyroid function.
Acta Med Scand.
1975;
197
(1–2)
15-17
-
20
Edson J R, Fecher D R, Doe R P.
Low platelet adhesiveness and other hemostatic abnormalities in hypothyroidism.
Ann Intern Med.
1975;
82
(3)
342-346
-
21
Manfredi E, van Zaane B, Gerdes V EA, Brandjes D P, Squizzato A.
Hypothyroidism and acquired von Willebrand's syndrome: a systematic review.
Haemophilia.
2008;
14
(3)
423-433
-
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
(2)
392-393
-
23
Baumgartner-Parzer S M, Wagner L, Reining G et al..
Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells.
J Endocrinol.
1997;
154
(2)
231-239
-
24
Rogers II J S, Shane S R, Jencks F S.
Factor VIII activity and thyroid function.
Ann Intern Med.
1982;
97
(5)
713-716
-
25
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
-
26
Silva J E, Bianco S D.
Thyroid-adrenergic interactions: physiological and clinical implications.
Thyroid.
2008;
18
(2)
157-165
-
27
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
(3)
323-329
-
28
Sievert R, Goldstein M L, Surks M I.
Graves' disease and autoimmune factor VIII deficiency.
Thyroid.
1996;
6
(3)
245-247
-
29
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
(3)
246-249
-
30
Huth-Kühne A, Baudo F, Collins P et al..
International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.
Haematologica.
2009;
94
(4)
566-575
-
31
Pengo V, Tripodi A, Reber G Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis et al.
Update of the guidelines for lupus anticoagulant detection.
J Thromb Haemost.
2009;
7
(10)
1737-1740
-
32
Hume R.
Fibrinolytic activity and thyroid function.
BMJ.
1965;
1
(5436)
686-688
-
33
Bennett N B, Ogston C M, McAndrew G M.
The thyroid and fibrinolysis.
BMJ.
1967;
4
(5572)
147-148
-
34
Marongiu F, Biondi G, Conti M et al..
Is a hypercoagulable state present in hypothyroidism?.
Thromb Haemost.
1992;
67
(6)
729
-
35
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
-
36
Chadarevian R, Jublanc C, Bruckert E et al..
Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism.
J Endocrinol Invest.
2005;
28
(5)
398-404
-
37
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
-
38
Willeit J, Kiechl S, Oberhollenzer F et al..
Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study.
Arterioscler Thromb Vasc Biol.
2000;
20
(2)
529-537
-
39
Razvi S, Shakoor A, Vanderpump M, Weaver J U, Pearce S H.
The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis.
J Clin Endocrinol Metab.
2008;
93
(8)
2998-3007
-
40
Mariotti S.
Mild hypothyroidism and ischemic heart disease: is age the answer?.
J Clin Endocrinol Metab.
2008;
93
(8)
2969-2971
-
41
Mari D, Mannucci P M, Coppola R, Bottasso B, Bauer K A, Rosenberg R D.
Hypercoagulability in centenarians: the paradox of successful aging.
Blood.
1995;
85
(11)
3144-3149
-
42
Weintraub M, Breckenridge R T, Griner P F.
The effects of dextrothyroxine on the kinetics of prothrombin activity: proposed mechanism of the potentiation of warfarin by D-thyroxine.
J Lab Clin Med.
1973;
81
(2)
273-279
-
43
Loeliger E A, Van Der Esch B, Mattern M J, Hemker H C.
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
-
44
Siu C W, Pong V, Zhang X et al..
Risk of ischemic stroke after new-onset atrial fibrillation in patients with hyperthyroidism.
Heart Rhythm.
2009;
6
(2)
169-173
-
45
Kurnik D, Loebstein R, Farfel Z, Ezra D, Halkin H, Olchovsky D.
Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland.
Medicine (Baltimore).
2004;
83
(2)
107-113
-
46
Bucerius J, Joe A Y, Palmedo H, Reinhardt M J, Biersack H J.
Impact of short-term hypothyroidism on systemic anticoagulation in patients with thyroid cancer and coumarin therapy.
Thyroid.
2006;
16
(4)
369-374
-
47
Bucerius J, Naubereit A, Joe A Y et al..
Subclinical hyperthyroidism seems not to have a significant impact on systemic anticoagulation in patients with coumarin therapy.
Thromb Haemost.
2008;
100
(5)
803-809
Francesco MarongiuM.D.
Professor, Dipartimento di Scienze Mediche Internistiche “Mario Aresu,” University of Cagliari
Cagliari, Italy; Policlinico Universitario di Monserrato, SS 554, bivio per Sestu, Momserrato (Cagliari), Italy
Email: marongiu@medicina.unica.it
