Introduction
Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. HbS is prone to polymerization upon deoxygenation, and this property underlies all the pathophysiology of SCD. The net result is a chronic hemolytic anemia, with intravascular and extravascular components, and a tendency for microvascular obstruction or vaso-occlusion (VOC). The ability to predict ''severe disease'' depends on the ability to define it specifically and reproducibly. Many genetic, clinical and laboratory modifiers have been suggested as possible predictors of a "severe disease". Despite of this wealth of data the modelling of predictor variable continues to be difficult (Quinn et al, 2016).
Considering that the hallmark of SCD is the chronic hemolitic anemia causing increasing of gastro-intestinal iron absorption, our aim was to evaluate if LIC-R2 (Ferriscan) determination may be related with phenotype severity of SCD.
Methods
This was a retrospective study of patients with SCD attending 7 Italian centres participating in the LICNET-S (Liver Iron Cutino NETwork in Sickle Cell Disease), collected at the Campus of Hematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello (Palermo, Italy). The LICNET-S protocol was established on June 2018 by Foundation Franco and Piera Cutino of Palermo and approved by our Ethics Committee on 4, July 2018. This analysis included data from LIC-R2 for those patients presenting between July 2018 and July 2019. The MRI-R2 used protocol was that of St Pierre et al, 2005. Retrieved information included laboratory and clinical findings. These are shown as mean±sd and percentages. A linear regression model (LRM) (Draper & Smith, 1998) was used to study the correlation between LIC-R2 and some potential indicators of phenotype severity. All statistical analyses were performed using Stata 12 (StataCorp, College Station, TX, USA).
Results
Overall 65 patients (32 (49.3%) females) whom 16 patients with S/S, 15 with S/beta+ tahalseemia and 34 with S/beta0 thalassemia were enrolled in the study.
Table 1 shows summary of the main clinical findings included in the study to evaluate the LIC-R2 predictivity based on SCD phenotype severity.
Table 2 shows the results of the LRM analysis. The variables statistically significant were the number of the VOC, the Aseptic Avascular Necrosis (AVN) and the Chelation Treatment (CT) (Table 2). However, transfusion regimen was not related with LIC-R2 value, suggesting that chronic hemolitic anemia causing increasing of gastro-intestinal iron absorption rather than transfusion treatment was the main determinant in the LIC-R2 values. This issue is supported by the report of high LIC-R2 in non transfused patients with SCD (Yassim et al, 2017). Table 2 shows even the relationship between the impairment of the single indicator (VOC, AVN, CT) and the LIC-R2 value. All other laboratory and main clinical findings included in Table 2 were not statistically significant. The value of VOC in determining phenotype severity is well known. AVN is a consequence of a chronic ischaemia with inflammatory process evolving at the same time as medullary osteoblastic activity (Mukizi-Musaka et al, 2010). Therefore, it may be related with the chronic hemolitic anemia condition in SCD. Finally, the relationship between CT and LIC-R2 may be explained considering that patients with higher iron body burden are those who received earlier chelation treatment.
Conclusions
This study suggests, as LIC-R2 value is a strong predictive indicator of phenotype severity in SCD. Probably, this is due because of LIC-R2 is related both with acute and chronic hemolitic anemia of SCD causing an increase, during the years, of gastro-intestinal iron absorption.
Therefore, the possibility of preventing VOC, even using new anti-sickling drugs, should be hardly pursued.
No relevant conflicts of interest to declare.
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