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.