Relationship between Thyroid Hormones and Plasma D-dimer Levels

Rita Chadarevian; Eric Bruckert; Annick Ankri; Isabel Beucler; Philippe Giral; Gérard Turpin

doi:10.1055/s-0037-1614228

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(01): 99-103
DOI: 10.1055/s-0037-1614228

Review Article

Schattauer GmbH

Relationship between Thyroid Hormones and Plasma D-dimer Levels

Rita Chadarevian

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

,

Eric Bruckert

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

,

Annick Ankri

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

,

Isabel Beucler

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

,

Philippe Giral

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

,

Gérard Turpin

From Service d’Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France

› Author Affiliations

Abstract

Summary

High serum levels of cholesterol and triglycerides are risk factors for coronary heart disease and are strongly related to several haemostatic parameters. Thyroid disorders are a frequent feature in hyperlipidemic patients and are also associated with a variety of haemostatic abnormalities. Therefore, we analysed the relationships between free T4 (fT4) levels and Factor VII and VIII activities (FVIIc and FVIIIc), D-Dimers (DDI) and Plasminogen Activator Inhibitor type 1 (PAI-1), in a group of 472 healthy patients referred for hyperlipidemia.

Fourty patients were found to have primary hypothyroidism. A negative correlation was found in the whole study population between fT4 and DDI (p = 0.0001, r = –0.21) and the same results were found after exclusion of the patients with fT4 below the normal range (p = 0.0007, r = –0.17). In a multivariate regression analysis, the relationship between DDI and fT4 was independent of age, Body Mass Index (BMI), gender and total cholesterol. Less impressive correlation coefficients were found with FVIIc (r = –0.10), FVIIIc (r = –0.09) and PAI-1 (r = –0.09).

These results suggest that fT4 may play a physiological role in the regulation of the haemostatic equilibrium in hyperlipidemic patients and that low levels of fT4 are associated with a hypercoagulable state.

Full Text

References

References
1 Zitoun D, Bara L, Basedevant A, Samama MM. Levels of factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias. Arterioscl, Thromb & Vasc Biol 1996; 16: 77-81.
2 Carvalho de Sousa J, Bruckert E, Giral P, Soria C, Truffert J, Mirshahi MC, de Gennes JL, Caen JP. Plasma factor VII, Triglyceride concentration and fibrin degradation products in primary hyperlipidemia: a clinical and laboratory study. Haemostasis 1989; 19: 83-90.
3 Mitropoulos KA, Miller GJ, Reeves BEA, Wilkes HC, Cruuicksank JK. Factor VII coagulant activity is strongly associated with the plasma concentration of large lipoproteins particles in middle-aged men. Atherosclerosis 1989; 76: 203-8.
4 Kannel WB, Castelli WP, Grodon R, and McNamara PM. Serum cholesterol, lipoproteins and the risk of coronary heart disease. The Framingham study. Ann Intern Med 1971; 14: 1-6.
5 Martin MJ, Hulley SB, Browner WS, Kuller LH, and Wentworth D. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 Men. Lancet 1986; i: 933-8.
6 Meade TW, Mellows S, Brozovic M, Miller GJ, Hakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: Principal results of Northwick Park Heart Study. Lancet 1986; 2: 533-7.
7 Bruckert E, De Gennes JL, Dairou F, Turpin G. Fréquence des hypothyroïdies dans une population de sujets hyperlipidémiques. Presse médicale 1993; 2: 57-60.
8 Diekman T, Lansberg PJ, Kastelein JJP, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Int Med 1995; 155: 1490-5.
9 Myrup B, Bregengard C, Faber JF. Primary haemostasis in thyroid disease. J Intern Med 1995; 238: 59-63.
10 Farid NR, Griffiths BL, Collins JR, Marshall WH, Ingram DW. Blood coagulation and fibrinolysis in thyroid disease. Thromb Haemost 1976; 35: 415-22.
11 Klein M, Barbé F, Kaminsky P, Duc M. Haemostatic disorders in thyroid dideases. Path Biol 1993; 41 N°3 268-75.
12 Van Oosterom AT, Kerkhoven P, Veltkamp JJ. Metabolism of the coagulation factors of the prothrombin complex in hypothyroidism in man. Thromb Haemost 1979; 41: 273-85.
13 Ford HC, Carter JM. Haemostasis in hypothyroidism. Postgrad Med J 1990; 66: 280-4.
14 Blesing NE, Hambley H, McDonald GA. Acquired Von Willebrand’s disease and hypothyroidism: report of a case presenting with menorrhagia. Postgrad Med J 1990; 66: 474-6.
15 Dalton RG, Savidge GF, Matthews KB, Dewar MS, Kernoff PBA, Greaves M, Preston FE. Hypothyroidism as a cause of acquired Von Willebrand’s disease. Lancet 1987; i: 1007-9.
16 Smith SR, Auger MJ. Hypothyroidism and Von Willebrand’s disease. Lancet 1987; i: 1314.
17 MacCallum PK, Rodgers M, Taberner DA. Hypothyroidism and Von Willebrand’s disease. Lancet 1987; i: 1314.
18 Thornton JG, Parapia LA, Minford AMB. Hypothyroidism and Von Willebrand’s disease. Lancet 1987; i: 1314-5.
19 Rogers JS, Shane SR, Jencks FS. Factor VIII activity and thyroid function. Ann Intern Med 1982; 97: 713-6.
20 Palareti G, Biagi G, Legnani C, Bianchi D, Serra D, Savini R, Coccheri S. Association of reduced factor VIII with impaired platelet reactivity to adrenalin and collagen after total thyroidectomy. Thromb Haemost 1989; 62: 1053-6.
21 Sterling K. Thyroid hormone action at the cellular level. N Engl J Med 1979; 300: 117-23.
22 De Feo P. Hormonal regulation of human protein metabolism. Eur J Endocrinol 1996; 135: 7-18.
23 Graninger W, Pirich KR, Speiser W, Deutsch E, Waldhausl WK. Effect of thyroid hormones on plasma protein concentration in man. J Clin Endocrinol Metab 1986; 63: 407-11.
24 Fowkes FGR, Lowe GDO, Housley E, Rattray A, Rumley A, Elton RA, MacGregor IR, Dawes J. Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart diseasse. Lancet 1993; 342: 84-6.
25 Herren T, Stricker H, Haeberli A, Do DD, Straub PW. Fibrin formation and degradation in patients with arteriosclerotic disease. Circulation 1994; 90: 2679-89.
26 Eisenberg PR, Sherman LA, Perez J, Jaffe AS. Relationship between elevated plasma levels of cross linked fibrin degradation products (XL-FDP) and the clinical presentation of patients with myocardial infarction. Thromb Res 1987; 46: 109-20.
27 Giansante C, Fiotti N, Cattin L, Da Col PG, Calabrese S. Fibrinogen, D-Dimer and thrombin-antithrombin complexes in a random population sample: Relationship with other cardiovascular risk factors. Thromb Haemost 1994; 71: 581-6.
28 Heinrich J, Balleisen L, Schulte H, Assmann G, Van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler & Thromb 1994; 14: 54-9.
29 Dalaker K, Smith P, Arnesen H, Prydz H. Factor VII-phospholipid complex in male survivors of acute myocardial infarction. Acta Med Scand 1987; 222: 111-6.
30 Cortellaro M, Cofrancesco E, Boschetti C, Zanussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, della Volpe A, Polli E. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. The PLAT group. Arterioscler & Thromb 1993; 3: 1412-7.
31 Wirman B. Plasminogen activator inhibitor 1 (PAI-1) in plasma: its role in thrombotic disease. Thromb Haemost 1995; 74: 71-6.
32 Geppert A, Beckman R, Graf S, Hornykewycz S, Lang I, Schuster E, Binder BR, Huber K. Tissue-type plasminogen activator and type-1 plasminogen activator inhibitor in patients with coronary artery disease – Relations to clinical variables and cardiovascular risk factors. Fibrinolysis 1995; 9: 109-13.
33 Cortellaro M, Boschetti C, Cofrancesco E, Zanussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, della Volpe A, Polli E. The PLAT study: Hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Arterioscler & Thromb 1992; 12: 1063-70.
34 Hoyer LW. The factor VIII complex: Structure and function. Blood 1981; 58: 1-13.
35 Ladenson PW. Recognition and management of cardiovascular disease related to thyroid dysfunction. Am J Med 1990; 88: 638-41.
36 Rogers JS, Shane SR. Factor VIII in normal volunteers receiving oral thyroid hormone. J Lab Clin Med 1983; 102: 444-9.
37 Van Oosterom AT, Mattie H, Hermens Th, Veltkamp J. The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and factor X in the rat. Thromb Haemost 1976; 35: 607-19.
38 Erfurth EM, Ericsson UB, Egervall K, Lethagen SR. Effect of acute desmopressin and of long-term thyroxine replacement on haemostasis in hypothyroidism. Clin Endocrinol 1995; 42: 373-8.
39 Polikar R, Burger AG, Scherrer U, Nicod P. The thyroid and the heart. Circulation 1993; 87: 1435-41.