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

Abstract

Subclinical hypothyroidism (SH) is associated with some abnormalities in primary and secondary hemostasis. The objective of the study was to evaluate changes in primary and secondary hemostasis induced by levothyroxine (L-T4) treatment in SH patients. This was a prospective cohort study with a 6-month follow-up. Outpatients were referred to "Federico II" University of Naples. Subjects with a SH without previous/ongoing L-T4 therapy participated in the study. 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. 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). SH patients exhibit a prothrombotic status, which is reverted by a 6-month L-T4 treatment.