Be more confident in appropriate anaemia diagnosis and therapy
Anaemia is the most common haematologic abnormality in patients with solid tumours and haematologic malignancies. Anaemia in oncological patients reflects multiple possible aetiological factors such as a result of nutritional deficiency, impaired RBC production or a side effect of chemotherapy. Iron deficiency is among the most common causes of anaemia and can develop in almost half of the patients with haematologic malignancies [1]. Functional iron deficiency is predominant, due to the underlying disease or therapy-related inflammatory processes [2].
Common laboratory parameters to assess the iron status such as ferritin and transferrin saturation (TSAT) are affected due to their role as acute-phase proteins and cannot reflect iron availability for erythropoiesis reliably [3,4]. The state-of-the-art Sysmex analysers offer a parameter that directly and reliably assesses the availability of iron for haemoglobinisation – the reticulocyte haemoglobin equivalent (RET-He ).
Benefits of having the reticulocyte haemoglobin equivalent analysed
- The reticulocyte haemoglobin equivalent (RET-He) reflects the haemoglobin content of reticulocytes – immature red blood cells preceding the mature RBC stage by a few days, and thereby giving an indication on the haemoglobinisation quality of new RBCs.
- It directly reflects the bioavailability of iron for erythropoiesis over the previous 2 – 4 days [5,6], independent of the acute-phase reaction – unlike TSAT and ferritin [3,4]
- Values below 29 pg or 1.80 fmol are indicative of functional iron deficiency [7] and thereby support therapy decision guidance in patients with solid tumours or haematologic malignancy
- Early indication of the response to iron therapy and/or erythropoiesis-stimulating agents [8,9]
- Affected by individual biological variation to a much lower degree than TSAT and ferritin [10]
Anaemia in lymphoma
A 60-year-old woman with a history of multiple medical conditions presented to the emergency department with acute upper gastrointestinal bleeding. She reported increasing weakness over weeks and repeated upper respiratory infections. The endoscopy revealed gastric ulcer, and a subsequent diagnosis of plasmablastic lymphoma was made. Initially, due to severe anaemia, the woman was transfused with one unit of RBC concentrate. The patient remained anaemic with reduced red cell parameters (HGB 7.7 g/dL or 4.78 mmol/L, HCT 22.4%).
Although reticulocytes were increased (RET 3.4%), the haemoglobin content of the reticulocytes was decreased (RET-He 26.8 pg or 1.66 fmol), indicating high reticulocyte turnover, but iron deficiency for their haemoglobinisation. Thus, the haematologist held off from an additional transfusion while an appropriate therapy of iron infusion was indicated, along with all other medical interventions. RET-He was found to be a more useful supporting parameter than the inconclusive, extremely elevated ferritin (1,100 ng/mL) and decreased TSAT (17%) values, both of which are acute-phase reactants.
Had only these parameters been ordered, the clinician could have mistakenly concluded that the patient was replete with iron and so missed the opportunity for appropriate anaemia therapy.
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References
[1] Ludwig H et al. (2013): Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. Jul; 24(7): 1886–1892.
[2] Aapro M et al. (2018): Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol. Oct 1; 29(Suppl 4): iv96–iv110.
[3] 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.
[4] Thomas C et al. (2002): Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem. Jul; 48(7): 1066–76.
[5] 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. Sep; 10(18): 4250.
[6] Hoenemann C et al. (2021): Reticulocyte Haemoglobin as a Routine Parameter in Preoperative Iron Deficiency Assessment. Endocrinol Metab Vol. 5 No.1: 154.
[7] Muñoz M et al. (2017): International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia. Feb; 72(2): 233–247.
[8] 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. Sep 26; 11(19): 5675.
[9] Auerbach M et al. (2021): Using Reticulocyte Hemoglobin Equivalent as a Marker for Iron Deficiency and Responsiveness to Iron Therapy. Mayo Clin Proc. Jun; 96(6): 1510–1519.
[10] 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. Sep; 56(3): 540–6.