مختصر البحث:
Background: Glycated hemoglobin (HbA1c) is the internationally
recognized gold standard to assess long-term glycemic control in patients with
diabetes mellitus. However, its efficacy is fundamentally undermined in
thalassemia syndromes, which ar…
Background: Glycated hemoglobin (HbA1c) is the internationally
recognized gold standard to assess long-term glycemic control in patients with
diabetes mellitus. However, its efficacy is fundamentally undermined in
thalassemia syndromes, which are one of the most prevalent inherited
hemoglobin disorders worldwide due to ineffective erythropoiesis, altered red
blood cell biology, chronic hemolysis, reduced red blood cell (RBC) lifespan,
and confounding factors related to transfusion. Despite precise glycemic
monitoring being clinically time-sensitive and urgent for thalassemia patients,
who have significantly raised risk of endocrine disorders such as diabetes
mellitus, a universally recognized clinical framework for addressing this
diagnostic challenge remains absent.
Objectives: This comprehensive review critically analyzes the mechanisms
through which different thalassemia subtypes, including α-thalassemia, β
thalassemia major (transfusion-dependent), β-thalassemia intermedia (non
transfusion-dependent), and compound hemoglobinopathies, influence HbA1c
measurement across accepted analytical system. This research further
assesses the evidence base for alternative glycemic indicators in thalassemia
populations and presents evidence-informed clinical recommendations.
Methods: A narrative systematic review was performed using
PubMed/MEDLINE, the Cochrane Library, Embase, and Google Scholar to
identify peer-reviewed publications from 2000 to 2025, with particular
emphasis on those published post-2015. The search terms used were
thalassemia, hemoglobin A1c, glycated hemoglobin, HbA1c interference,
fructosamine,
glycated
albumin,
continuous
glucose
monitoring,
hemoglobinopathy, diabetes mellitus, iron overload, and erythrocyte lifespan.
Results: The alpha-thalassemia trait does not substantially affect HbA1c
assessment in standard high-performance liquid chromatography (HPLC)
techniques. Conversely, HbH disease causes significant measurement errors in
cation-exchange HPLC systems due to peak co-elution. The β-thalassemia trait
is linked to a statistically significant, yet clinically minor, decrease in HbA1c
levels, primarily resulting from a decrease in hemoglobin concentration.
Transfusion-dependent β-thalassemia compromises the accuracy of HbA1c
measurement through several procedures including Glycated albumin,
fructosamine, and continuous glucose monitoring (CGM) offer clinically
relevant, although not flawless, alternatives for glycemic evaluation in
thalassemia settings.
Conclusion: Clinicians treating thalassemia patients with suspected or co
existing diabetes must exercise caution when interpreting HbA1c results,
identify method-specific analytical limits, and consistently use alternative
glycemic monitoring strategies. Efficient multidisciplinary coordination among
diabetologists, hematologists, and clinical laboratorians is essential for
achieving optimal glycemic surveillance and reducing the risk of both under
andover-treatment of diabetes among patients with thalassemia
