Primary and Secondary Hemostasis in Patients With Subclinical Hypothyroidism: Effect of Levothyroxine Treatment
Open accessAbstract
CONTEXT: Subclinical hypothyroidism (SH) is associated with some abnormalities in primary and secondary hemostasis. OBJECTIVE: The objective of the study was to evaluate changes in primary and secondary hemostasis induced by levothyroxine (L-T4) treatment in SH patients. DESIGN: This was a prospective cohort study with a 6-month follow-up. STUDY SETTING: Outpatients were referred to "Federico II" University of Naples. PATIENTS: Subjects with a SH without previous/ongoing L-T4 therapy participated in the study. MAIN OUTCOME MEASURE: Changes in major hemostatic/fibrinolytic variables and platelet reactivity [mean platelet volume (MPV), arachidonic acid (AA), or ADP concentrations inducing a ≥ 50% irreversible aggregation (AC-50%)] in SH patients before and after a 6-month L-T4 treatment. RESULTS: At baseline, 41 SH patients showed higher levels of factor VII activity (123.9 ± 20.4 vs 107.7 ± 12.2, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 vs 22.5 ± 5.74, P < .001) and tissue plasminogen activator (5.56 ± 2.22 vs 4.75 ± 1.61, P = .010), with lower levels of D-dimer (220.3 ± 67.1 vs 252.1 ± 72.4, P = .017) compared with healthy controls. SH patients also showed a higher MPV (9.92 ± 1.15 vs 8.9 ± 0.9, P < .001) and AC-50% to AA (0.18 ± 0.12 vs 0.36 ± 0.10, P < .001) and to ADP (1.5 ± 0.6 vs 1.9 ± 1.3, P = .024). After a 6-month L-T4 therapy, a reduction of factor VII activity (from 123.9 ± 20.4 to 102.6 ± 14.3, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 to 19.4 ± 7.6, P < .001), and tissue plasminogen activator (5.56 ± 2.22 to 1.91 ± 4:43, P = .002) was found in SH subjects, with a marginal increase in D-dimer (from 220.3 ± 67.1 to 245.2 ± 103.1, P = .053). AC-50% to AA (from 0.18 ± 0.12 to 0.54 ± 0.3, P < .001) and to ADP (from 1.5 ± 0.6 to 1.86 ± 0.3, P = .042) were reduced, paralleled by a significant reduction of MPV (from 9.92 ± 1.15 to 9.10 ± 1.23, P = .016). CONCLUSIONS: SH patients exhibit a prothrombotic status, which is reverted by a 6-month L-T4 treatment.
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Subclinical hypothyroidism is paradoxically associated with a shift to a procoagulant state, with higher FVII, PAI-1, and tissue plasminogen activator, which seem to normalise with 6 months of LT4.
“Subclinical hypothyroidism is paradoxically associated with a shift to a procoagulant state, with higher FVII, PAI-1, and tissue plasminogen activator (t-PA), which seem to normalise with 6 months of LT4”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [107]
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- Authors
- 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.
- Affiliations
- Centro Cardiologico Monzino (IT)
- Corresponding author
- Lupoli, Roberta
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-07
- Volume
- 100
- Issue
- 7
- Pages
- 2659-2665
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1914359976
- Cited by
- 26
- References
- 42
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 1 · 2015: 1
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- 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
- subclinical hypothyroidism, levothyroxine, primary hemostasis, secondary hemostasis, fibrinolysis, platelet reactivity, factor VII activity, plasminogen activator inhibitor-1, tissue plasminogen activator, D-dimer, mean platelet volume, platelet aggregation, arachidonic acid, ADP-induced aggregation
- MeSH terms
- Adult, Female, Fibrinolysis, Follow-Up Studies, Hemostasis, Humans, Hypothyroidism, Male, Middle Aged, Platelet Aggregation, Thyroxine, Asymptomatic Diseases, Mean Platelet Volume
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