Direct Assessment of the Availability of Iron for Hemoglobinization

Direct Assessment of the Availability of Iron for Hemoglobinization

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Functional iron deficiency (FID) is a state in which iron incorporation into erythroid precursor cells is insufficient despite apparently normal body iron stores. The most common test to determine functional iron availability is the assessment of transferrin saturation (TSAT). However, TSAT may be affected by factors that are unrelated to iron status, such as infection and inflammation. A sensitive and easily accessible blood test marker would therefore be desirable to rapidly evaluate the iron that is directly available for hemoglobin synthesis. There is a parameter backed with evidence from studies that can be used: Sysmex’s reticulocyte hemoglobin equivalent (RET-He).

What is RET-He?

  • Hematology parameter which reflects the hemoglobin content of reticulocytes – immature red blood cells.
  • May assist with an early assessment of the available iron that was utilized in the red blood cell production over the previous 2–4 days.1,2
  • Reference range: 29.3–35.4 pg.3
  • Studies show high accuracy and precision.4,5
  • Test methodology is based on fluorescence flow cytometry.
  • Readily available from a routine EDTA (K2 or K3) blood sample analysis in the laboratory.

 

Case of functional iron deficiency*

A 68-year-old female with symptoms of fatigue and difficulty completing activities of daily life presented to her nephrologist. She was suffering from Stage III chronic kidney disease due to polycystic kidney disease. The blood count revealed anemia with a decreased hemoglobin (9.9 g/dL) and reticulocyte hemoglobin equivalent (27.4 pg). Due to underlying inflammation, traditional tests such as serum iron (36 μg/dL), ferritin (788 ng/mL) and TSAT (15%) were not fully conclusive but indicated functional iron deficiency. The patient was referred for the administration of erythropoiesis stimulating agents (ESA) to promote the production of red blood cells. Supplemental iron was given prior to ESA therapy to ensure adequate hemoglobinization of the new red blood cells. The patient completed five weeks of I.V. iron therapy with good response already one week after the therapy was initiated, with RET- He levels increasing to 29.8 pg. This increase in RET- He helped clinicians to understand the improved availability of iron for hemoglobinization and corroborated the effectiveness of treatment.6 This was further substantiated by the patient’s reduction in symptoms.

*Results of case studies are not predictive of other cases and results may vary.

Benefits of RET-He with functional iron deficiency

  • Assesses the content of hemoglobin in reticulocytes
  • Reflects the bioavailability of iron for erythropoiesis, comparable to transferrin saturation1,10
  • Studies indicate it is unaffected by acute-phase reactants (such as inflammation)7,8
  • Research shows it exhibits less biological variation compared to TSAT and ferritin9

 

References

[1] Hoenemann C et al. (2021): Reticulocyte and Erythrocyte Hemoglobin Parameters for Iron Deficiency and Anemia Diagnostics in Patient Blood Management. A Narrative Review. J Clin Med; 10(18): 4250.
[2] Hoenemann C et al. (2021): Reticulocyte Haemoglobin as a Routine Parameter in Preoperative Iron Deficiency Assessment. Endocrinol Metab; Vol. 5 No.1: 154.
[3] L van Pelt J et al. (2022): Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort. Clin Chem Lab Med; 60(6): 907–920.
[4] Buttarello M et al. (2016): Evaluation of the hypochromic erythrocyte and reticulocyte hemoglobin content provided by the Sysmex XE-5000 analyzer in diagnosis of iron deficiency erythropoiesis. Clin Chem Lab Med; 54(12): 1939–1945.
[5] Mehta S et al. (2016): Reticulocyte Hemoglobin vis-a-vis Serum Ferritin as a Marker of Bone Marrow Iron Store in Iron Deficiency Anemia. J Assoc Physicians India; 64(11): 38–42.
[6] Almashjary MN et al. (2022): Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity. J Clin Med; 11(19): 5675.
[7] Thomas L et al. (2005): Reticulocyte hemoglobin measurement-comparison of two methods in the diagnosis of iron-restricted erythropoiesis. Clin Chem Lab Med; 43(11): 1193–202.
[8] Thomas C et al. (2002): Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem; 48(7): 1066–76.
[9] Van Wyck DB et al. (2010): Analytical and biological variation in measures of anemia and iron status in patients treated with maintenance hemodialysis. Am J Kidney Dis; 56(3): 540–6.
[10] Shander A et al. (2022): Recommendations from the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS). Ann Surg; 277(4): 581-590.

 



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