Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism
Abstract
Objective: The aims of the study were to evaluate the disturbances in the coagulation system in patients with overt hypothyroidism (OH), to assess the effects of levothyroxine (LT4) on the coagulation parameters, and to determine whether subclinical hypothyroidism (SH) affects concentrations of coagulation markers and several biochemical parameters, thereby supporting early substitution. Design: The study included 15 patients with SH (TSH levels 5–10 mU/l), 15 patients with OH and 15 euthyroid controls. Methods: Blood urea nitrogen, creatinine, creatine phosphokinase, aspartate aminotransferase, lactate dehydrogenase, total-cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol and triglyceride levels, and bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), factor VIII activity, von Willebrand factor activity (vWF), platelet count and clotting time were evaluated just before and three months after the maintenance of euthyroidism with LT4 treatment. Results: Factor VIII and vWF activities were lower in patients with SH than in controls (P< 0.01). Increased bleeding time, PT, APTT and clotting time and decreased factor VIII activity and vWF activity were observed in patients with OH when compared with controls. Bleeding time, PT, APTT and clotting time decreased and factor VIII activity, vWF and platelet count increased after LT4 in patients with OH. Increases in factor VIII activity and vWF (P< 0.01) were detected also in the SH group with treatment. Conclusions: OH is associated with significant abnormalities in clotting parameters which are reversed by LT4. In contrast, SH is associated with minor changes in factor VIII activity and vWF which are reversible by LT4. Serum lipids and other measured parameters are not improved by LT4 in patients with TSH < 10 mU/l and these data fail to demonstrate a need to treat such patients.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Correction of TSH levels to normal using LT4 replacement corrects these abnormalities.
“Correction of TSH levels to normal using LT4 replacement correct these abnormalities”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [102]
Low levels of circulating thyroid hormone shift the haemostatic system to a hypocoagulable hyper-fibrinolytic state, with reduced Factors VIII, IX, and XI and von Willebrand factor that are normalised on LT4.
“low levels of circulating thyroid hormone shift the haemostatic system to a hypocoagulable hyper-fibrinolytic state, with reduced Factors VIII, IX, and XI and von Willebrand factor (VWF) that are normalised on LT4”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [102]
Cites
Subclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management
Surks, M. I., Ortiz, E., Daniels, G. H., Sawin, C. T., Col, N. F., Cobin, R. H., Franklyn, J. A., Hershman, J. M., Burman, K. D., Denke, M. A., et al. (2004) · JAMA · doi:10.1001/jama.291.2.228 · Cited by 1,800 · see citing works
A double‐blind, placebo‐controlled trial
Pinals, R. S., Kaplan, S. B., Lawson, J. G., & Hepburn, B. (1986) · Arthritis & Rheumatism · doi:10.1002/art.1780291202 · Cited by 1,355 · 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
L-Thyroxine Therapy in Subclinical Hypothyroidism: A Double-Blind, Placebo-Controlled Trial
COOPER, D. S., HALPERN, R., WOOD, L. C., LEVIN, A. A., & RIDGWAY, E. C. (1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-1-18 · Cited by 423 · see citing works
Danese, M. D., Ladenson, P. W., Meinert, C. L., & Powe, N. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.9.2993 · Cited by 423 · see citing works
Subclinical Hypothyroidism Is Mild Thyroid Failure and Should be Treated
McDermott, M. T., & Ridgway, E. C. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7959 · Cited by 398 · see citing works
Meier, C., Staub, J.-J., Roth, C.-B., Guglielmetti, M., Kunz, M., Miserez, A. R., Drewe, J., Huber, P., Herzog, R. F. K., & Müller-Stich, B. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7973 · Cited by 397 · see citing works
Danese, M. D., Ladenson, P. W., Meinert, C. L., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6841 · Cited by 308 · see citing works
Nyström, E., Caidahl, K., Fager, G., Wikkelsø, C., Lundberg, P. A., & Lindstedt, G. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb00250.x · Cited by 306 · see citing works
Caraccio, N., Ferrannini, E., & Monzani, F. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.4.8378 · Cited by 294 · 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
The Treatment of Subclinical Hypothyroidism Is Seldom Necessary
Chu, J. W., & Crapo, L. M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7961 · Cited by 231 · see citing works
A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism
Kong, W. M., Sheikh, M. H., Lumb, P. J., Freedman, D. B., Crook, M. A., Doré, C. J., & Finer, N. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01022-7 · Cited by 223 · see citing works
Vanderpump, M. P. J., Tunbridge, W. M. G., French, J. M., Appleton, D. R., Bates, D., Clark, F., Evans, J. G., Rodgers, H., Tunbridge, F. K. E., & Young, E. T. (1996) · PubMed · doi:10.1089/thy.1996.6.155 · Cited by 207 · see citing works
Clinical and Biochemical Features of Muscle Dysfunction in Subclinical Hypothyroidism
Monzani, F., Caraccio, N., Siciliano, G., Manca, L., Murri, L., & Ferrannini, E. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4296 · Cited by 147 · see citing works
Components of the Fibrinolytic System Are Differently Altered in Moderate and Severe Hypothyroidism
Chadarévian, R., Bruckert, É., Leenhardt, L., Giral, P., Ankri, A., & Turpin, G. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7221 · Cited by 138 · see citing works
Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease
Müller, B., Tsakiris, D. A., Roth, C. B., Guglielmetti, M., Staub, J. ‐., & Marbet, G. A. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00777.x · Cited by 136 · see citing works
Blood Volumes and Renal Function in Overt and Subclinical Primary Hypothyroidism
Villabona, C. M., de la Vega, M. S., Gómez, N., Gómez, J. M., Soler, J., Roca, M., Mora, J., & Puchal, R. (1999) · The American Journal of the Medical Sciences · doi:10.1016/s0002-9629(15)40631-7 · Cited by 123 · see citing works
Thyroxine replacement therapy and circulating lipid concentrations
Franklyn, J., Daykin, J., Betteridge, J., Hughes, E., Holder, R., Jones, S., & Sheppard, M. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb00339.x · Cited by 115 · see citing works
Thyroid Hormone Receptor-Dependent Transcriptional Regulation of Fibrinogen and Coagulation Proteins
Shih, C., Chen, S. L., Yen, C.-C., Huang, Y., Chen, C.-D., Lee, Y., & Lin, K. (2004) · Endocrinology · doi:10.1210/en.2003-1372 · Cited by 114 · see citing works
END‐ORGAN RESPONSES TO THYROXINE THERAPY IN SUBCLINICAL HYPOTHYROIDISM
BELL, G. M., TODD, W. T. A., FORFAR, J. C., MARTYN, C., WATHEN, C. G., GOW, S., RIEMERSMA, R., & TOFT, A. D. (1985) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1985.tb01068.x · Cited by 112 · see citing works
Subclinical Thyroid Dysfunction
Woeber, K. A. (1997) · Archives of Internal Medicine · doi:10.1001/archinte.1997.00440310023002 · Cited by 107 · 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
Cantürk, Z., Çetinarslan, B., Tarkun, İ., Cantürk, N. Z., Yüce, M. Ö., & Duman, C. (2003) · Thyroid · doi:10.1089/105072503322511382 · Cited by 93 · see citing works
Acquired von Willebrand Syndrome Type 1 in Hypothyroidism: Reversal After Treatment With Thyroxine
Michiels, J. J., Schroyens, W., Bememan, Z., & van der Planken, M. (2001) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/107602960100700206 · Cited by 81 · see citing works
Serum Creatine Kinase Levels in Overt and Subclinical Hypothyroidism
Beyer, I., Karmali, R., Demeester-Mirkine, N., Cogan, E., & Fuss, M. (1998) · Thyroid · doi:10.1089/thy.1998.8.1029 · Cited by 77 · 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
Blood Volumes and Renal Function in Overt and Subclinical Primary Hypothyroidism
Villabona, C. M., Sahún, M. J. S., ROCA, M., et al. (1999) · The American Journal of the Medical Sciences · doi:10.1097/00000441-199910000-00007 · Cited by 71 · see citing works
Serum creatine, creatinine, and other guanidino compounds in patients with thyroid dysfunction
Verhelst, J. A., Berwaerts, J., Marescau, B., et al. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90279-1 · Cited by 70 · see citing works
BLOOD COAGULATION AND FIBRINOLYTIC ACTIVITY IN HYPOTHYROIDISM
Erem, C., Kavgacı, H., Ersöuz, H., Hacıhasanoğlu, A., Ükinç, K., Karti, S. S., Değer, O., & Telatari, M. (2003) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2003.tb10430.x · Cited by 64 · 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
Acquired Von Willebrand's Disease
Jakway, J. L. (1992) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(18)30283-1 · Cited by 44 · see citing works
Coagulation and Fibrinolysis in Thyroid Disease
Rennie, J. A. N., Bewsher, P. D., Murchison, L. E., et al. (2009) · Acta Haematologica · doi:10.1159/000207759 · Cited by 41 · see citing works
Subclinical hypothyroidism: epidemiology, diagnosis, and significance.
Arem, R., & Escalante, D. (1996) · PubMed · Cited by 41 · see citing works
Alteration of platelet aggregation in patients with thyroid disorders
Masunaga, R., Nagasaka, A., Nakai, A., Kotake, M., Sawai, Y., Oda, N., Mokuno, T., Shimazaki, K., Hayakawa, N., Kato, R., et al. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90203-1 · Cited by 34 · see citing works
Palareti, G., Biagi, G., Legnani, C., Bianchi, D., Serra, D., Savini, R., & COCCHERI, S. (1989) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1647116 · Cited by 32 · see citing works
Acquired von Willebrand's Syndrome Causing a Hemorrhagic Diathesis in a Patient with Hypothyroidism
Attivissimo, L., Lichtman, S. M., & Klein, I. L. (1995) · Thyroid · doi:10.1089/thy.1995.5.399 · Cited by 23 · see citing works
Advances in Internal Medicine.
(1943) · Archives of Internal Medicine · doi:10.1001/archinte.1943.00210020164011 · Cited by 13 · see citing works
Hypopituitarism, Deficiency of Factors V and VIII and von Willebrand Factor: An Uncommon Association
Setian, N., Tanaka, C. M., Damiani, D., et al. (2002) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2002.15.3.331 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
IQBAL, A., JORDE, R., & FIGENSCHAU, Y. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01652.x · Cited by 174 · see citing works
Erem, C. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02464.x · Cited by 136 · see citing works
The influence of thyroid function on the coagulation system and its clinical consequences
Elbers, L. P. B., Fliers, E., & Cannegieter, S. C. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13970 · Cited by 123 · see citing works
Levothyroxine (LT<sub>4</sub>) suppression treatment for benign thyroid nodules alters coagulation
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
Akinci, B., Demir, T., Comlekci, A., Yener, S., Ozcan, M. A., Karaoglu, O., Yuksel, F., Secil, M., & Yesil, S. (2011) · Medical Principles and Practice · doi:10.1159/000322074 · Cited by 7 · see citing works
Pharmacodynamic and Therapeutic Actions of Levothyroxine
Hennessey, J. V. (2021) · 70 Years of Levothyroxine · doi:10.1007/978-3-030-63277-9_3 · Cited by 4 · see citing works
- Authors
- Gullu, S., Sav, H., & Kamel, N.
- Affiliations
- Ankara University (TR)
- ORCID
- Sav, Hasan
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-03
- Volume
- 152
- Issue
- 3
- Pages
- 355-361
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2129985458
- Cited by
- 96
- References
- 41
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- levothyroxine, overt hypothyroidism, subclinical hypothyroidism, coagulopathy, hemostasis, factor VIII activity, von Willebrand factor, bleeding time, prothrombin time, activated partial thromboplastin time, serum lipids, thyroid hormone replacement
- MeSH terms
- Adult, Aged, Factor VIII, Female, Hemostasis, Humans, Hypothyroidism, Middle Aged, Severity of Illness Index, Thyroid Function Tests, Thyroid Gland, Thyroxine, von Willebrand Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review