Protein carbonylation as a modulator of fibrin clot properties in thyroid disorders: impact of therapy

TL;DR

This study shows that protein carbonylation, a sign of oxidative stress, affects blood clot properties in thyroid disorders and is reduced after treatment.

Contribution

The study reveals the role of protein carbonylation in altering fibrin clot properties in thyroid disorders and its response to therapy.

Findings

Hyperthyroid and hypothyroid patients had elevated protein carbonylation compared to controls.

Protein carbonylation was linked to denser fibrin clots and impaired fibrinolysis in hyperthyroid patients.

Thyroid hormone normalization reduced protein carbonylation and altered clot properties mainly in hypothyroid patients.

Abstract

Protein carbonylation (PC), a marker of oxidative stress, was shown to be elevated in both hyperthyroid and hypothyroid disorders. These conditions are associated with unfavorable fibrin clot properties. We sought to investigate whether elevated PC is associated with prothrombotic markers in hyperthyroid and hypothyroid individuals before and following effective therapy. We studied 31 hyperthyroid, 29 hypothyroid patients, and 29 sex- and age-matched controls. Along with plasma total PC content, we measured fibrin clot properties (fibrin clot permeability, Ks; clot lysis time, CLT), fibrinolysis proteins, and thrombin generation before and after 3-month successful therapy. Hyperthyroid patients had a tendency to higher PC (+ 9.1%; p = 0.05), while hypothyroid individuals had 17.2% higher PC (p = 0.01) compared with controls, without any difference between the patient groups. Pre-treatment PC inversely correlated with Ks in both hyper- (R=-0.425, p = 0.017) and hypothyroid (R=-0.510, p = 0.005) individuals, while solely in hyperthyroid patients PC was associated with CLT (R = 0.556, p = 0.001), but not with fibrinolysis inhibitors, or other hemostatic markers. On-treatment PC, which decreased by 19.6% (p < 0.001) in hyperthyroid and by 23.4% (p < 0.001) in hypothyroid patients reaching the control levels, was associated with Ks (R=-0.401, p = 0.031) and CLT (R = 0.537, p = 0.003) only in the hypothyroid group. In hyper- and hypothyroid patients elevated PC may contribute to formation of more compact fibrin clot networks with impaired fibrinolysis in the former group. Reduced PC following thyroid hormone normalization maintained its impact on fibrin clot properties solely in hypothyroid patients, which indicates complex effects of oxidative stress on blood coagulation.

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