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. 2023 Nov 8;12(11):1982.
doi: 10.3390/antiox12111982.

Stratification of βSβ+ Compound Heterozygotes Based on L-Glutamine Administration and RDW: Focusing on Disease Severity

Aimilia Giannaki  1 , Hara Τ Georgatzakou  1 , Sotirios P Fortis  1 , Alkmini T Anastasiadi  1   2 , Efthimia G Pavlou  1   3 , Efrosyni G Nomikou  3 , Maria P Drandaki  4 , Angeliki Kotsiafti  4 , Aikaterini Xydaki  4 , Christina Fountzoula  5 , Effie G Papageorgiou  1 , Vassilis L Tzounakas  2 , Anastasios G Kriebardis  1
Affiliations

Stratification of βSβ+ Compound Heterozygotes Based on L-Glutamine Administration and RDW: Focusing on Disease Severity

Aimilia Giannaki et al. Antioxidants (Basel). .

Abstract

Sickle cell disease (SCD) is heterogeneous in terms of manifestation severity, even more so when in compound heterozygosity with beta-thalassemia. The aim of the present study was to stratify βSβ+ patient blood samples in a severity-dependent manner. Blood from thirty-two patients with HbS/β-thalassemia compound heterozygosity was examined for several parameters (e.g., hemostasis, inflammation, redox equilibrium) against healthy controls. Additionally, SCD patients were a posteriori (a) categorized based on the L-glutamine dose and (b) clustered into high-/low-RDW subgroups. The patient cohort was characterized by anemia, inflammation, and elevated coagulation. Higher-dose administration of L-glutamine was associated with decreased markers of inflammation and oxidation (e.g., intracellular reactive oxygen species) and an altered coagulation profile. The higher-RDW group was characterized by increased hemolysis, elevated markers of inflammation and stress erythropoiesis, and oxidative phenomena (e.g., membrane-bound hemoglobin). Moreover, the levels of hemostasis parameters (e.g., D-Dimers) were greater compared to the lower-RDW subgroup. The administration of higher doses of L-glutamine along with hydroxyurea seems to attenuate several features in SCD patients, probably by enhancing antioxidant power. Moreover, anisocytosis may alter erythrocytes' coagulation processes and hemolytic propensity. This results in the disruption of the redox and pro-/anti-inflammatory equilibria, creating a positive feedback loop by inducing stress erythropoiesis and, thus, the occurrence of a mixed erythrocyte population.

Keywords: L-glutamine; RDW; coagulation; inflammation; oxidative stress; sickle cell disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cluster analysis revealed two subgroups stratified by RDW values.
Figure 2
Figure 2
Differences in (A) hemolysis markers and (B) redox parameters between SCD samples stratified by their RDW values. Inserts: immunoblots of selected samples for high (H) and low (L) RDW subgroups. The 4.1R protein was used as an internal loading control. TAC: total antioxidant capacity; UAdAC: uric-acid-dependent antioxidant capacity; UAiAC: uric-acid-independent antioxidant capacity; ROS: reactive oxygen species; MFI: mean fluorescence intensity; Hb: hemoglobin. (*) p < 0.05.
Figure 3
Figure 3
Differences in hemostasis and coagulation parameters between SCD samples stratified by their RDW values. PT: prothrombin time; INR: international normalized ratio; APTT: activated partial thromboplastin time; TAT: thrombin–antithrombin; EV: extracellular vesicles; PS: phosphatidylserine. (*) p < 0.05.
Figure 4
Figure 4
Differences in indicators of inflammation between SCD samples stratified by their RDW values. (*) p < 0.05.
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