HI Morteza , I think first of all , You should  exclude thalassemic trait  ( Carrier ).

in y country Hb electrophoresis as thalassemia is a possibility , iron status next

You need to check both haemoglobin electrophoresis and iron status. Likely diagnosis is, as suggested by Fatma and Abdul Majeed, thalassaemia trait.

Siva

Iron studies.  Also look at rbc numbers vs. hemoglobin/hematocrit. If higher than expected,  prob thal minor.  I would not spend money on hem electrophoresis that would identify only beta thal in any case.

Hi,

We see results like the above scenario often. Because of the over riding need to prioritize spending costs, we don't usually bother with iron studies since IDA (if indeed present) will in addition most likely manifest with depression in MCH, MCHC, elevated RDW and marked aniso-poikilocytosis, hypochromia,  targets etc on peripheral blood film examination. Due to low health insurance coverage, such patients are commonly stratified into those that can afford further work up and those that cannot. The former will do Hb Quantification with HPLC to rule out Thal trait,  while the latter group will have to be followed us on 3 monthy basis with PCV and blood film review, this will determine the extent and time to intervene more actively.  

And in the meantime a patient with early iron deficiency and a possibke operable g.i. carcinoma is turned into an incurable state??!! Sounds like a poor trade off of health care resources! 

Low MCV (in isolation) is not synonymous with IDA!

I think basically we have to start with Hb electrophoresis, since in the presence of normal Hb, thalassemia minor is the likely possibility. This test will help us diagnose Beta thalassemia minor (increased Hb A2) or Delta beta thalassemia carrier state (increased F, reduced or normal A2). The next step if this is normal is to do iron studies. If this is also normal then by exclusion the possibility of Alpha thalassemia trait should be considered. The latter could only be confirmed by molecular studies.

The study of a patient with anemia begins with the examination, examination

Physical examination and basic laboratory tests, namely: complete blood count, count

Of reticulocytes and platelets, iron profile (ferremia, transferrinemia,

Saturation of transferrin and serum ferritin), erythrocyte sedimentation, hepatogram,

Renal function, thyroid profile, LDH and serum haptoglobin.

Initial Algorithm

According to the hematimetric indexes, the absolute reticulocyte count and

The presence of other cytopenias suggests an orientative algorithm.

The hematimetric indexes and the absolute reticulocyte count allow us to

To perform a morphological classification of anemia.

Faced with an anemic picture it is important to distinguish whether they are engaged

Other cell lines, establishing a global defect of hematopoiesis. The

Tricitopenia may occur in severe megaloblastic anemia but also

In other haematological charts such as medullary aplasia, myelodysplastic syndromes

(SMD) or by infiltration of the bone marrow. When the indices are

Are all diminished, we will have microcytic and hypochromic anemias,

As is the case of iron deficiencies, thalassemias, sideroblastic anemias

And those of the chronic processes. Iron deficiencies usually present higher RDW

Than thalassemic syndromes. The initial phases of deficiency anemia occur

With VCM and normal reticulocytes and with hematocrits not so low (32% - 33%).

Normocytic, normochromic anemia with elevated reticulocytes should be

Hemolysis or acute hemorrhage. Hemolytic pictures can also be

Have a high VCM since the reticulocytes are young and large cells.

A high VCM with reticulocytes and normal RDW is almost exclusive to one

Myelodysplastic Syndrome. Characterizes to the medullary insufficiencies a VCM

High with very reduced reticulocytes. In megaloblastic anemias, if there is

Deficiency of iron, reticulocytes are often low, otherwise

May be within normal range but never increased (unless

Initiated treatment).

With these guiding bases the etiopathogenesis of anemia should be ascertained,

For which the antecedents (personal, familiar, labor, medicated,

Etc.), as well as other symptoms and signs (eg, urine color,

Ulcers, mane, etc.) to request specific determinations that allow the

Diagnostic confirmation.

Iron deficiency anemia, is common problem, first lab. finding may be MCV changes, close follow up as well as monitoring RBCs count if very important to exclude thalassemia minor which is not uncommon 

In the case described by Dr. Salimian we have a normal level of total haemoglobin with microcytosis (decreased MVC). Because smaller RBCs  have a lower haemoglobin content (MCH) a normal level of total haemoglobin can be achieved only increasing the  RBC production. This pathophysiological consideration excludes the hypothesis of iron deficiency anaemia because this (in addition with reduced MCV and MCH) is characterized by decreased Hb concentration in RBC (decreased MCHC = hypochromia) as well as decreased RBC production. Because  the RBC count at  value of 5x1012/L  as cut-off is a reliable parameter for distinguishing thalassemia and iron deficiency in patients with microcytosis  (Johansen JML et al. CCLM 2015  53(12): 1883-1894), the beta-thalassemic trait in this case must be the first diagnostic hypothesis. 

In the absence of iron deficiency and anaemia of chronic disease, thalassaemia trait (heterozygous beta thalasaemia or alpha thalassaemia due to single / 2 gene deletion) is most likely. A simple formula known as the Mentzer index will be able to distinguish iron deficiency from thalassaemia trait. Divide the MCV by the red cell count: an MCV/RCC ratio

What does it means " young males"? If they are 18 years old can be blood donnors? and can have that kind of parameters between donations! We have that experience is like a therapeutic phlebotomy in the PV patients.

I think it's better firtst have a  good clinical history, knowing the results from CBC of the relatives, look for the RDW value and for the smear morphology!  You have to do reticulocyte count I and if you have the CHr parameter in your analyzer can be very usefull because it decrease if the patient have IDA. After all you can do HPLC or molecular studies. 

Best regards

Rogerio Barreira

The association between IDA and Thalassaemic trait is not infrequent: so in these cases the diagnosis is more complicate. However we must remember that the patient of dr. Salimian is not anaemic ( "normal level of Hb, HCT and RBC count"). These data in presence of microcytosis are more indicative for thalassaemic trait, probably with Hb and RBC count in lower and upper limits of respective normal ranges.

I would like to appreciate all colleagues for their valuable comments on my question. As Dr.Gioia  mentioned, the point is that those patients are not anemic,  some of them show even  a high Hb level. A mild decrease of  Hb concentration is supposed to be  occur  in the case of  Thal trait.( with low MCV, Low MCH and increased RBC count. ). Please consider the following case; male 27 y CBC; (WBC 7.53,R.B.C

5.92, Hb 16.2,  HCT 46.3, M.C.V  78.21,  M.C.H 27.36, M.C.H.C 34.99, RDW-SD

37.4,  RDW-CV 13.2)). How can we explain  the mild decrease of  MCV , while  Hb concentration is 16.2?

one thing you need to consider with figures you quoted.. is whether your instrument has been properly calibrated.. the clue is a general trend towards lower MCV.. one other explanation maybe if the patient is a known case of PV on regular phlebotomy.. such patients would have high Hb with microcytic indices due to development of concomitant iron deficiency. though this particular patient is rather young for such a diagnosis

I am curious to know whether alpha thalassemia trait was considered in this case??? I would be strongly tempted to think of that in this case as its mild microcytosis with normal Hb and RBC count towards the upper end of normal. I would also think of delta beta thal in cases with minimal microcytosis and normal Hb although the RBC count tends to be lower than the case that has been described here...

According to Dr. Arunachalan the diagnosis of heterozygous alfa thalassemia can be considered if the study of haemoglobin does not show anomalies suggesting a beta thalassemia (i.e. increased HbA2). IDA must be previously excluded or iron balance could be corrected before any further investigation.The same considerations can be made for heterozygous delta/beta thalassemia.

Yes a HPLC analysis would clear things up quite a bit. High HbA2 would suggest a beta thal although beta thal trait having a Hb of 16.2 is little unlikely. If its a normal or especially low normal HbA2 i would think of alpha thal first as iron deficiency alone (except maybe early/latent ones) doesn't correlate with the given Hb or RBC count. And of course a heterozygous silent beta thalassemia would also be a possibility in this case.

Must be and IDS or a thalassemia or both simultaneously in the same patient

In addition, V617F Jak-2 analysis and erithropoietin level could be useful. based on the HGB value, IDA is unlikely but very easy to exclude with ferritin measurement.