Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease
Abstract
The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0.02) and the ratio FVII:C/FVII:Ag (P < 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.
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In subclinical hypothyroidism, factor VII activity and the factor VII activity-to-factor VII antigen ratio are significantly increased in women compared with controls.
“In SCH, factor VII activity and the factor VII activity-tofactor VII antigen ratio were significantly increased in women with SCH compared with controls(66).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [66]
Cites
THE SPECTRUM OF THYROID DISEASE IN A COMMUNITY: THE WHICKHAM SURVEY
Tunbridge, W. M. G., Evered, D. C., Hall, R., Appleton, D. R., BREWIS, M., CLARK, F., Evans, J. G., Young, E. T., Bird, T., & Smith, P. (1977) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1977.tb01340.x · Cited by 2,665 · see citing works
Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women
Grady, D., Rubin, S. M., Petitti, D. B., Fox, C. S., Black, D. M., Ettinger, B. B., Ernster, V. L., & Cummings, S. R. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-12-1016 · Cited by 2,329 · see citing works
Postmenopausal Estrogen Therapy and Cardiovascular Disease
Stampfer, M. J., Colditz, G. A., Willett, W. C., Manson, J. E., ROSNER, B. A., Speizer, F. E., & Hennekens, C. H. (1991) · New England Journal of Medicine · doi:10.1056/nejm199109123251102 · Cited by 2,000 · see citing works
Meade, T. W., Brozović, M., Chakrabarti, R., Haines, A., Imeson, J., Mellows, S., Miller, G. J., North, W. R. S., Stirling, Y., & Thompson, S. G. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90111-x · Cited by 1,937 · see citing works
Thompson, S. G., Kienast, J., Pyke, S., Haverkate, F., & van de Loo, J. C. W. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503093321003 · Cited by 1,819 · see citing works
Hak, A. E., Pols, H. A. P., Visser, T. J., Drexhage, H. A., Hofman, A., & Witteman, J. C. M. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-4-200002150-00004 · Cited by 1,336 · see citing works
Koster, T., Vandenbroucke, J. P., Rosendaal, F. R., Briët, E., Rosendaal, F. R., & Blann, A. D. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90166-3 · Cited by 1,131 · see citing works
MEADE, T. (1993) · The Lancet · doi:10.1016/0140-6736(93)92062-x · Cited by 711 · see citing works
Postmenopausal Estrogen Therapy and Cardiovascular Disease
MacLean, D. B., & Bostom, A. G. (1992) · New England Journal of Medicine · doi:10.1056/nejm199203053261012 · Cited by 703 · see citing works
Heinrich, J., Balleisen, L., Schulte, H., Assmann, G., & van de Loo, J. (1994) · Arteriosclerosis and Thrombosis: A Journal of Vascular Biology · doi:10.1161/01.atv.14.1.54 · Cited by 563 · see citing works
Staub, J.-J., Althaus, B., Engler, H., Ryff, A., Trabucco, P., Marquardt, K., BURCKHARDT, D., Girard, J., & Weintraub, B. D. (1992) · The American Journal of Medicine · doi:10.1016/0002-9343(92)90782-7 · Cited by 317 · see citing works
Self-citationThompson, P. L., Aylward, P. E., Federman, J., Harris, P., Hodge, R. L., Latt, N. K. Z., Pitt, A., Thomson, A. G., Tonkin, A. M., Byrne, A. C., et al. (1988) · The Lancet · Cited by 284 · see citing works
LDL/HDL‐CHANGES IN SUBCLINICAL HYPOTHYROIDISM: POSSIBLE RISK FACTORS FOR CORONARY HEART DISEASE
Althaus, B., Staub, J. J., LÈCHE, A. R., OBERHÄNSLI, A., & Stähelin, H. B. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb03651.x · Cited by 243 · see citing works
Self-citationTracy, R. P., Arnold, A. M., Ettinger, W. H., Fried, L. P., Meilahn, E. N., & Savage, P. J. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.7.1776 · Cited by 198 · see citing works
Ritter, A. (1955) · De Gruyter eBooks · doi:10.1515/9783110881707 · Cited by 194 · see citing works
Aillaud, M.-F., Amouyel, P., Evans, A., Luc, G., Ferrières, J., Arveiler, D., Juhan-Vague, I., & Scarabin, P. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615353 · Cited by 184 · see citing works
Impaired Action of Thyroid Hormone Associated with Smoking in Women with Hypothyroidism
Müller-Stich, B. P., Zulewski, H., Huber, P., Ratcliffe, J. G., & Staub, J.-J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199510123331503 · Cited by 166 · see citing works
Self-citationCoagulation Factor VII and the Risk of Coronary Heart Disease in Healthy Men
Junker, R., Heinrich, J., Schulte, H., van de Loo, J., & Assmann, G. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.8.1539 · Cited by 163 · see citing works
PRECLINICAL HYPOTHYROIDISM: A RISK FACTOR FOR CORONARY HEART-DISEASE*1
Bastenie, P. A. (1971) · The Lancet · doi:10.1016/s0140-6736(71)90947-0 · Cited by 152 · see citing works
The Effects of Transdermal Estradiol and Oral Conjugated Estrogens on Haemostasis Variables
Kroon, U. ‐., Silfverstolpe, G., & Tengborn, L. (1994) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1642453 · Cited by 147 · see citing works
HYPOTHYROIDISM AS A CAUSE OF ACQUIRED VON WDLLEBRAND'S DISEASE
Dalton, R. G., Savidge, G. F., Matthews, K. B., et al. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92272-0 · Cited by 130 · see citing works
Balleisen, L., Assmann, G., Bailey, J., Epping, P.-H., Schulte, H., & van de Loo, J. (1985) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1660106 · Cited by 114 · see citing works
Hypothyroidism: Diversity of Presentation
Ml, T., & Guthrie, G. P. (1984) · Endocrine Reviews · doi:10.1210/edrv-5-3-456 · Cited by 112 · see citing works
Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease?
Tièche, M., Lupi, G. A., Gutzwiller, F. S., Grob, P. J., Studer, H., & Bürgi, H. (1981) · Heart · doi:10.1136/hrt.46.2.202 · Cited by 109 · see citing works
Factor VIII Activity and Thyroid Function
Rogers, J., SHANE, S. R., & JENCKS, F. S. (1982) · Annals of Internal Medicine · doi:10.7326/0003-4819-97-5-713 · Cited by 103 · see citing works
Coagulation disorders in thyroid diseases
Hofbauer, L. C., & Heufelder, A. E. (1997) · European Journal of Endocrinology · doi:10.1530/eje.0.1360001 · Cited by 95 · see citing works
Quehenberger, P., Loner, U., Kapiotis, S., Handler, S., Schneider, B., Huber, J. C., & Speiser, W. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650651 · Cited by 75 · see citing works
Primary haemostasis in thyroid disease
MYRUP, B., BREGENGÅRD, C., & FABER, J. (1995) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1995.tb00899.x · Cited by 72 · see citing works
Loeliger, E. A., van der Esch, B., Mattern, M. J., & Hemker, H. C. (1963) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1654782 · Cited by 70 · see citing works
Relationship between Thyroid Hormones and Plasma D-dimer Levels
Bruckert, É., Ankri, A., Beucler, I., Giral, P., Turpin, G., & Chadarévian, R. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614228 · Cited by 63 · see citing works
Ford, H. C., & Carter, J. M. (1990) · Postgraduate Medical Journal · doi:10.1136/pgmj.66.774.280 · Cited by 57 · see citing works
Relationship between thyroid hormones and fibrinogen levels
Chadarévian, R., Bruckert, É., Giral, P., et al. (1999) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199912000-00005 · Cited by 52 · see citing works
van Baal, W. M., Kooistra, T., & Stehouwer, C. D. A. (2000) · Current Medicinal Chemistry · doi:10.2174/0929867003374967 · Cited by 52 · see citing works
Raised serum thyrotrophin in women with peripheral arterial disease
Powell, J. T., Zadeh, J. A., Carter, G., Greenhalgh, R. M., & Fowler, P. B. S. (1987) · British journal of surgery · doi:10.1002/bjs.1800741220 · Cited by 49 · see citing works
Bruckert, É., Giral, P., Chadarévian, R., & Turpin, G. (1999) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1177/204748739900600510 · Cited by 48 · see citing works
Regulation of the Procoagulant Response to Arterial Injury
Giesen, P. L. A., Schecter, A., Nemerson, Y., & Taubman, M. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615914 · Cited by 45 · see citing works
Determinants of Population Changes in Fibrinogen and Factor VII Over 6 Years
Folsom, A. R., Wu, K. K., Rasmussen, M. L., Chambless, L. E., Aleksic, N., & Nieto, F. J. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.2.601 · Cited by 42 · see citing works
Risk factors for cerebrovascular disease and the role of coagulation and fibrinolysis
Catto, A. J., & Grant, P. J. (1995) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199509000-00001 · Cited by 40 · see citing works
ECAT Assay Procedures A Manual of Laboratory Techniques
(1992) · Springer eBooks · doi:10.1007/978-94-011-2992-3 · Cited by 34 · see citing works
Serum-derived growth factor is thrombin?
Schwartz, S. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116197 · Cited by 30 · see citing works
Plasma Factor VIla: Measurement and Potential Clinical Significance
Morrissey, J. H. (2009) · Haemostasis · doi:10.1159/000217243 · Cited by 26 · see citing works
Activated and Total Coagulation Factor VII, and Fibrinogen in Coronary Artery Disease
Danielsen, P. T. Ö. R. (1998) · Scandinavian Cardiovascular Journal · doi:10.1080/14017439850140238 · Cited by 25 · see citing works
Subir�, M., Mateo, J., Souto, J. C., Alt�s, A., & Fontcuberta, J. (1999) · American Journal of Hematology · doi:10.1002/(sici)1096-8652(199903)60:3 · Cited by 22 · see citing works
Metabolism of the Coagulation Factors of the Prothrombin Complex in Hypothyroidism in Man
van Oosterom, A. T., Kerkhoven, P., & Veltkamp, J. J. (1979) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1646646 · Cited by 19 · see citing works
Is a Hypercoagulable State Present in Hypothyroidism?
Marongiu, F., Biondi, G., Conti, M. V., et al. (1992) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1648535 · Cited by 19 · see citing works
Fr, O. (1962) · The Lancet · doi:10.1016/s0140-6736(62)92701-0 · Cited by 17 · see citing works
Flagged first, then by citations
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The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418 · see citing works
Thyroid hormones and cardiovascular disease
Jabbar, A., Pingitore, A., Pearce, S. H. S., Zaman, A., Iervasi, G., & Razvi, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.174 · Cited by 729 · see citing works
Thyroid Hormones and Cardiovascular Function and Diseases
Razvi, S., Jabbar, A., Pingitore, A., Danzi, S., Biondi, B., Klein, I., Peeters, R., Zaman, A., & Iervasi, G. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.02.045 · Cited by 515 · see citing works
Effects of Thyroid Hormone on the Cardiovascular System
Fazio, S. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.31 · Cited by 445 · see citing works
Kvetny, J., Heldgaard, P. E., Bladbjerg, E. M., & Gram, J. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02088.x · Cited by 280 · see citing works
Erem, C. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02464.x · Cited by 136 · see citing works
Thyrotropin Levels and Risk of Fatal Coronary Heart Disease: The HUNT Study
Åsvold, B. O., Bjøro, T., Nilsen, T. I. L., Gunnell, D., & Vatten, L. J. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.8.855 · Cited by 125 · see citing works
Gullu, S., Sav, H., & Kamel, N. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01857 · Cited by 96 · see citing works
Cardiovascular risk in elderly hypothyroid patients
Mariotti, S., & Cambuli, V. M. (2007) · Thyroid · doi:10.1089/thy.2007.0130 · Cited by 44 · see citing works
Global fibrinolytic capacity in patients with subclinical hypothyroidism
GULDIKEN, S., DEMIR, M., TURGUT, B., ALTUN, B. U., ARIKAN, E., & KARA, M. (2005) · Endocrine Journal · doi:10.1507/endocrj.52.363 · Cited by 37 · see citing works
Lupoli, R., Di Minno, M. N. D., Tortora, A., Scaravilli, A., Cacciapuoti, M., Barba, L., Di Minno, A., Ambrosino, P., Lupoli, G. A., & Lupoli, G. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1726 · Cited by 26 · see citing works
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Demir, T., Akinci, B., Comlekci, A., Karaoglu, O., Ozcan, M. A., Yener, S., Yuksel, F., Secil, M., & Yesil, S. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03497.x · Cited by 13 · see citing works
- Authors
- Müller, B., Tsakiris, D. A., Roth, C. B., Guglielmetti, M., Staub, J. ‐., & Marbet, G. A.
- Affiliations
- University Hospital of Basel (CH)
- Corresponding author
- Tsakiris, D. A.
- Roth, C. B.
- Guglielmetti, M.
- Staub, J.‐J.
- Marbet, G. A.
- ORCID
- Tsakiris, D. A.
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2001-02
- Volume
- 31
- Issue
- 2
- Pages
- 131-137
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- OpenAlex
- W2066654051
- Cited by
- 136
- References
- 46
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 2 · 2012: 11
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- subclinical hypothyroidism, hemostasis, hypercoagulability, factor VII activity, factor VII antigen, prothrombin time, activated partial thromboplastin time, von Willebrand factor, antithrombin III, plasminogen activator inhibitor, thromboembolic risk, coronary artery disease, thyroxine replacement, women
- MeSH terms
- Adult, Blood Coagulation, Blood Coagulation Factors, Coronary Thrombosis, Female, Humans, Hypothyroidism, Middle Aged, Partial Thromboplastin Time, Prothrombin Time, Risk Factors
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