A variety of equations have been proposed to distinguish the microcytic anemia of iron deficiency from that of thalassemia minor.
These formulas may not be applicable:
(1) if the patient has been treated with iron;
(2) if the patient has been treated with blood transfusions;
(3) if both iron deficiency and thalassemia minor coexist in the same patient
(4) in some patients with polycythemia vera who develop iron deficiency (England-Fraser formula)
Some of the formulas do not account for a gray, intermediate region where it is not possible to differentiate between the two conditions reliably.
Mentzer Formula
Overview:
The Mentzer formula is a commonly used calculation to help identify patients who may have thalassemia.
Mentzer formula =
= ((MCV) / (red blood cell count))
where:
MCV is the mean corpuscular volume as measured in femtoliters
The red blood cell count is the number of red blood cells per L, divided by 10^6.
Interpretation:
Iron deficiency is indicated by a value > 13.
Thalassemia minor is indicated by a value < 13.
England-Fraser Formula
The England-Fraser formula is intended to help in distinguishing between thalassemia and other causes of microcytosis.
England-Fraser formula =
= ((MCV) - ((5 * (hemoglobin)) + (RBC) + K))
where:
MCV is the mean corpuscular volume as measured in femtoliters
hemoglobin is in g/dL
RBC is the number of red blood cells per L, divided by 10^6
K = 3.4 if the hematocrit is corrected for plasma trapping (usual situation) or 8.4 if it is not.
Interpretation:
no differentiation: formula > 0 (positive)
thalassemia minor: formula < 0 (negative)
If the hemoglobin electrophoresis is normal and England-Fraser result negative in the absence of iron deficiency, then alpha thalassemia minor likely.
Limitations:
The England-Fraser formula may provide only poor discrimination between thalassemia and non-thalassemic causes of microcytosis.
In patients with polycythemia vera who develop iron deficiency, a negative value for the England-Fraser formula may result.
The validity of the discriminant function may depend on the relative proportions of patients with iron-deficiency anemia and thalassemia in the population being examined.
M / H Ratio
In thalassemia microcytes exceed hypochromic cells. In iron deficiency, hypochromic cells exceed microcytes. The ratio of microcytes (M) to hypochromic cells (H) can help distinguish thalassemia from iron deficiency anemia.
Patient selection: presence of hypochromic anemia
Parameters (as originally determined on the Techinicon H*1 automated analyzer):
(1) M = percentage of cells that are microcytes (erythrocytes with volume less than 60 femtoliters)
(2) H = percentage of cells that are hypochromic (erythrocytes with hemoglobin less than 28 g/dL MCHC)
ratio =
= M / H
Interpretation:
A ratio < 0.9 indicates iron deficiency.
A ratio > 0.9 indicates thalassemia minor.
A ratio = 0.9 is indeterminate.
Limitations:
Mixed thalassemia minor and iron deficiency is relatively common.
Algorithm of Mulherin et al for the Diagnosis of Iron Deficiency Anemia vs Anemia of Chronic Disease in a Patient with Rheumatoid Arthritis
Serum ferritin levels may be elevated in patients who have both iron deficiency and chronic inflammation, making the distinction between iron deficiency anemia and the anemia of chronic disease difficult. Mulherin et al developed a simple algorithm based on simple laboratory measures to help diagnose anemia in patients with rheumatoid arthritis. The authors are from Dublin , Ireland
Step 1: Does the patient have rheumatoid arthritis? (If "yes" proceed, else stop).
Step 2: Is the patient anemic? (for males, hemoglobin < 11 g/dL; for women, hemoglobin < 10.5 g/dL)
Step 3: Is the serum ferritin < 40 g/L? (If "no", proceed to Step 4; if "yes", iron deficiency.)
Step 4: Is the MCV > 85 fL? (If "no", proceed to Step 5; if "yes", anemia of chronic disease).
Step 5: Is the percent iron saturation < 7%? (If "no", anemia of chronic disease; if "yes", iron deficiency.)
Observations:
(1) The algorithm should be applicable to other patients with autoimmune disease.
(2) The age range for the patients was 20 to 80 years.
(3) The study involved 45 patients. I would be interested to see the algorithm validated in a larger group, and to see whether any of the patients classified as anemia of chronic disease responded to iron therapy.
Green and King Formula
The Green and King formula uses red cell indices to help identify the cause of microcytosis.
formula of Green and King =
= ((((MCV)^2) * (RDW)) / ((hemoglobin) * 100))
where:
MCV is the mean red cell volume as measured in femtoliters
RDW is the red cell distribution width
hemoglobin is in g/dL
Interpretation:
iron deficiency: > 72
thalassemia minor: < 72
MCH / RBC Ratio
The MCH-to-RBC ratio is another calculation using red cell indices to help identify the possible cause of microcytosis.
MCH-to-RBC ratio =
= (MCH) / (red blood cell count)
where:
MCH is mean cell hemoglobin as measured in picograms
red blood cell count is the number of red blood cells per L, divided by 10^6
Interpretation:
iron deficiency: >4.4
thalassemia minor: < 4.4
The product of RDW times HDW can be used with automated red cell analyzers to help identify patients who may have thalassemia.
product of RDW and HDW =
= (RDW) * (HDW)
where:
RDW is the red cell distribution width
HDW
Interpretation:
iron deficiency: formula > 530
thalassemia minor: formula < 530
Note: I assume that HDW is in g/L. If g/dL (as from the Technicon) are used, the discriminant value becomes 53.
RDW / RBC Ratio
The RDW-to-RBC ratio is another calculation using red cell indices to help identify the possible cause of microcytosis.
RDW-to-RBC ratio =
=(RDW) / (RBC)
where:
RDW is the red cell distribution width
red blood cell count is the number of red blood cells per L, divided by 10^6
Interpretation:
iron deficiency: > 3.3
thalassemia minor: < 3.3
This is a screening tool for differentiating heterozygous beta-thalassemia from healthy subjects. It cannot discriminate between beta-thalassemia and iron deficiency.
Shine-Lal formula =
= (((MCV)^2) * (MCH)) / 100
where:
MCV is the mean corpuscular volume as measured in femtoliters
MCH is the mean corpuscular hemoglobin as measured in picograms
Interpretation:
thalassemia minor: < 1530.
