Primary and Secondary Hemostasis in Patients With Subclinical Hypothyroidism: Effect of Levothyroxine Treatment

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.