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Screening of IDA and Thalassemia made simple

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Divya Munshi

In the Indian context, the two most common etiologies for microcytic hypochromic anaemia cases are iron deficiency anaemia and beta thalassemia (a genetic haemoglobinopathy). As per the WHO estimate, 80 per cent of children, 58 per cent of pregnant women, 30 per cent adults in India are suffering from iron deficiency anaemia (IDA) while 3.3 per cent of Indian population is affected by beta thalassemia.

In regions like Punjab, Gujarat, Rajasthan, IDA and beta thalassemia co-exist with the former being prevalent and latter present in 6.5 per cent, 15 per cent and three per cent of their population respectively. This makes the task further difficult in the differentiation of borderline IDA and thalassemic cases.

Utility of automated RBC indices, for screening and differentiation of IDA and beta-thalassemia:

With the advent of automation in haematology, the first line of screening of IDA and thalassemia is possible through Complete Blood Count (CBC). An automated haematology analyser reports complete RBC count, Hb, MCV, MCH, MCHC which fall low in cases of microcytic anaemia.

However, the key automated haemogram indices which help in providing first line of differentiation among such cases of IDA and thalassemia are RDW-SD, RDW-CV in combination with MCV, Automated Reticulocyte Counts and IRF (Immature Reticulocyte Counts).

Red cell Distribution Width (RDW) is a quantitative measurement of variation in red cell size provided as either Standard Deviation (RDW-SD) or Co-efficient of Variation (RDW-CV). RDW-SD is measured by calculating the width in fl. (femto litre) at a relative height of 20 per cent above baseline of RBC curve. On the other hand, RDW-CV is measured by calculating ratio of 1SD of RBC curve to Mean Corpuscular Volume (MCV).

Calculation of RDW-SD and RDW-CV

Calculation of RDW-SD and RDW-CV

Both RDW-CV and RDW-SD reflect the variability in erythrocyte size and thus measure anisocytosis, however, each of these parameters has its own clinical utility. RDW-SD is a direct measure across the RBC histogram, hence it is ‘theoretically’ a better and more accurate measure of RBC anisocytosis across the entire spectrum of MCV values. On the other hand, RDW-CV shows better correlation as an indicator of anisocytosis, if the MCV is in the normal range and when the anisocytosis may be difficult to detect e.g early stage of IDA. While most analysers report, either RDW-SD or RDW-CV, some recent analysers provide ‘Simultaneous reporting of RDW-SD and RDW-CV’. Simultaneous reporting of these two indices helps in screening and differentiating IDA and thalassemia.

Other than RDW, Ret counts and IRF (Immature Reticulocyte Counts) available on high end 5PDA systems and have been identified as a useful adjunct in diagnosis and management of the above mentioned pathological conditions. According to published reports, Ret counts and IRF have been found to be high in cases of beta thalassemia minor and iron deficiency anemia respectively.

 
MCV High
MCV Normal
MCV Low
RDW-CV High B12/ Folate deficiency, CLL, Cold agglutinins Early Fe or B12 folate deficiency, Anaemic haemoglobinopathy, Sideroblastic myelofibrosis Fe deficiency, Hgb-H, Red cell fragments
RDW-CV Normal Aplastic anaemia Chemotherapy, Non-anemic haemoglobinopathy, CLL Heterozygous thalassemia, Chronic disease
RDW-SD High B12 deficiency, Aplastic anaemia, Immune haemolysis Acute/ Chronic leukaemia, Transfusion, Homozygous haemoglobinopathy Iron deficiency, Haemolytic anaemia
RDW-SD Normal Liver disease Secondary anemia Early iron deficiency
RDW-SD Low Chemotherapy (during treatment) Heterozygous hemoglobinopathies- Thalassemia  

Classification of Anaemia based on RDW-CV and RDW-SD in combination with MCV

Determination of the MCV is routinely used in the classification of normocytic, microcytic and macrocytic anemia. MCV when used in combination with RDW-CV and RDW-SD, serves as the best criteria for the classification of anemia. As the MCV is an arithmetic mean, it may exclude partial microcytosis – even in the reference range. Only in combination with the RDW-CV and RDW SD, it may indicate dimorphic erythrocytes, for example, the initial stages of iron deficiency.

The table highlights the importance of RDW-CV, RDW-SD and MCV in differentiation and prognosis of various anaemic conditions:

Case studies: Illustrating the importance of RDW-CV and RDW-SD in differential screening

Case 1: Iron Deficiency Anemia Case 2: Beta Thalassemia Minor

The above mentioned two case studies clearly depict low MCV typical of microcytic hypochromic anaemia. In case 1, RDW-CV of 20.5per cent is indicative of red cell anisocytosis consistent with iron deficiency anaemia, later confirmed with iron studies. Whereas in case 2, RDW-SD of 25.6 per cent which is below normal indicative of a monotonous red cell population consistent with beta thalassemia minor, later confirmed with Hb electrophoresis.

Given the prevalence of IDA and genetic haemoglobinopathies like thalassemia in India, availability of the simultaneous reporting of RDW-CV and RDW-SD on automated haematology analysers, goes a long way in screening these pathological conditions.

Sysmex haematology analysers allow a ‘Simultaneous reporting of RDW-SD and RDW-CV’ alongwith various specialised parameters like Reticulocyte and IRF which help in timely diagnosis of haemoglobinopathies.

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