Hepcidin Levels in Sickle Cell Disease (SCD)
Condition: Sickle Cell Anemia; Sickle - Beta Thalassemia
MeSH terms: Anemia, Sickle Cell; Thalassemia; beta-Thalassemia
Study type: Observational

Summary: 
      The investigators propose that patients with HbSβ-thalassemia have lower levels of hepcidin
      and higher levels of GDF-15 than HbSS patients during the non-crisis, "steady states." In
      addition, the investigators propose that when controlled for RBC transfusion, patients with
      HbSβ-thalassemia will have higher levels of storage iron (based on serum ferritin).

      Participants: Total number of subjects is 42 - 21 subjects with HbSS, and 21 subjects with
      HbSβ-thalassemia ).

      Procedures (methods): Eligible subjects with documented SCD (HbSS, HbS-β 0-thalassemia or
      HbS-β+-thalassemia) followed at the University of North Carolina (UNC) Comprehensive Sickle
      Cell Program will be evaluated in this single-center, prospective, cross-sectional study. The
      patients will be screened for eligibility at the time of a routine sickle cell clinic visit.
      Patients' data will be obtained in person at the time of evaluation and through review of
      their medical records. Investigators will obtain information on SCD-related clinical
      complications and obtain an estimate of the number of lifetime RBC transfusions. Blood
      samples will be obtained for laboratory tests. Plasma samples for hepcidin, growth
      differentiation factor 15 (GDF -15), and high-sensitivity CRP will be stored at -80 degrees
      Celsius until analysis. Other routine laboratory studies including complete blood count (CBC)
      with differential and reticulocyte count, serum iron profile and ferritin, and liver function
      tests will be performed at the clinical laboratories of UNC Hospitals.The subjects will have
      30 ml. of blood drawn for this research study. Females of child bearing potential will have a
      urine pregnancy test at the time of the study.
    

Detailed description: 
      Sickle cell disease (SCD) refers to a group of inherited disorders characterized by the
      presence of sickle hemoglobin (HbS) that are associated with episodes of acute illness and
      progressive organ damage. The most common variant of SCD, sickle cell anemia (HbSS), refers
      to homozygosity for the β S allele, with most of the remaining patients having sickle
      hemoglobin C disease (HbSC) and sickle beta thalassemia (HbSβ-thalassemia).

      SCD may be associated with iron overload that occurs following repeated red blood cell (RBC)
      transfusions. However, in patients with beta thalassemia major, iron overload occurs due to
      both repeated RBC transfusions and hyperabsorption of iron. The hyperabsorption of iron in
      beta thalassemia occurs due to ineffective erythropoiesis and subsequent downregulation of
      hepcidin. Thalassemia intermedia and major are the most studied human models of hepcidin
      modulation by ineffective erythropoiesis alone and the combined and opposite effect of both
      ineffective erythropoiesis and transfusion dependent iron overload, accordingly. Regular
      transfusions induce massive iron loading but inhibit erythropoietic drive. Accordingly,
      hepcidin production is higher in thalassemia major than in thalassemia intermedia although
      still inappropriate to the massive transfusional iron loading that partially counteracts the
      erythropoietic-dependent hepcidin down-regulation (Origa R et al, 2007; Kattamis A et al,
      2006; Camberlein E et al, 2008). No differences in the steady-state levels of hepcidin was
      observed when HbSS patients (N = 40) were compared with healthy hemoglobin AA (HbAA)controls
      (N = 30) (85.3 ± 30 l μg/L vs. 83.5 ± 40 l μg/L) (Ezeh C et al, 2005).

      Hepcidin is a 25-amino acid peptide produced mainly in the liver and is the major
      physiological regulator of body iron stores and serum iron. It negatively regulates egress of
      iron from cells, such as intestinal epithelial cells and macrophages. Growth differentiation
      factor-15 (GDF-15) and twisted gastrulation protein homolog 1(TWSG1), two transforming growth
      factor-β (TGF-β) superfamily members released from erythroid precursors, have been proposed
      to contribute to hepcidin suppression in thalassemia, although it remains unresolved whether
      GDF-15 and TWSG1 are markers of ineffective erythropoiesis or mediators of hepcidin
      suppression in vivo.

      With the presence of a thalassemia gene, patients with HbSβ-thalassemia (HbSβ0-thalassemia
      and HbSβ+-thalassemia) may have an increased tendency to absorb excess iron compared to
      patients with HbSS.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited from the population followed in the Adult Sickle Cell Clinic
        with either HbSS or HbS-βthalassemia who meet the eligibility criteria for the study.
      
Keywords: sickle cell disease