Reticulocyte production index

Reticulocyte

Erythrocyte

The Reticulocyte production index (RPI, also called a corrected reticulocyte count) is a calculated value used in the diagnosis of anemia. This calculation is necessary because the raw reticulocyte count is misleading in anemic patients. The problem arises because the reticulocyte count is not really a count but rather a percentage: it reports the number of reticulocytes as a percentage of the number of red blood cells. In anemia, the patient's red blood cells are depleted, creating an erroneously elevated reticulocyte count.

^[1]

Physiology

Reticulocytes are newly produced red blood cells. They are slightly larger than totally mature red blood cells, and have some residual ribosomal RNA. The presence of RNA allows a visible blue stain to bind or, in the case of fluorescent dye, result in a different brightness. This allows them to be detected and counted as a distinct population.^[2]

The idea of the RPI is to assess whether the bone marrow is producing an appropriate response to an anemic state. Reticulocyte production should increase in response to any loss of red blood cells. It should increase within 2–3 days of a major acute hemorrhage, for instance, and reach its peak in 6–10 days.^[3] If reticulocyte production is not raised in response to anemia, then the anemia may be due to an acute cause with insufficient time to compensate, or there is a defect with red blood cell production in the bone marrow. Marrow defects include nutritional deficiencies (i.e. iron, folate, or B12) or insufficient erythropoietin, the stimulus for red blood cell production. Reticulocytopenia, or "aplastic crisis", is the medical term for an abnormal decrease of reticulocytes in the body

The reticulocyte percentage index may find new use as a more reliable detector of erythropoietin-doping in athletes. The use of this method is referred to as "biological passport."

Calculation of RPI

Reticulocyte Production Index is calculated as follows:

1.$Retic Index = Retic Count * {Hematocrit \over Normal Hematocrit}$

A value of 45 is usually used as a normal hematocrit.^[4]

2.The next step is to correct for the longer life span of prematurely released reticulocytes in the blood—a phenomenon of increased red blood cell production. This relies on a table:

Hematocrit (%)	Retic survival (days) = maturation correction
36-45	1.0
26-35	1.5
16-25	2.0
15 and below	2.5

So, in a person whose reticulocyte count is 5%, hemoglobin 7.5 g/dL, hematocrit 25%, the RPI would be:

$RPI = {Retic Index \over Maturation Correction}$ → RPI $= {{5 * {25 \over 45}} \over 2} =$1.4

Alternatively some books provide the following formula:

$RPI = Retic Count * {Hemoglobin(observed) \over Normal Hemoglobin}*0.5$

Interpretation

• The reticulocyte index (RI) should be between 0.5% and 2.5% for a healthy individual.^[5]
• RI < 2% with anemia indicates loss of red blood cells, but decreased production of reticulocytes (i.e., an inadequate response to correct the anemia) and therefore red blood cells.^[2]
• RI > 3% with anemia indicates loss of red blood cells (from causes such as destruction, bleeding, etc.), with an increased compensatory production of reticulocytes to replace the lost red blood cells.^[2]

Interpretation of these values are not standard and vary based on specific laboratory values and clinical context. ^[6]

References

1. Callaway (2011). "Racing Just To Keep Up". Nature 475: 283. doi:10.1038/475283a.
2. Adamson JW, Longo DL. Anemia and polycythemia. in: Braunwald E, et al. Harrison's Principles of Internal Medicine. (15th Edition). McGraw Hill (New York), 2001.
3. Hoffbrand AV, et al. Essential Haematology. (Fourth Edition) Blackwell Science (Oxford), 2001.
4. "UAB Hematopathology". Retrieved 2009-02-07.
5. Hoffbrand, A.V, Moss, P.A.H, (2011), Essential Haemotology,6th Ed, Wiley and Blackwell; West Sussex, UK.
6. http://www.sysmex.ru/files/articles/Xtra_online_reticulocytes.pdf