General medicine

ANEMIA

Introduction

Evaluation for anemia is one of the most common problems in clinical practice. The evaluation may be straightforward in an otherwise healthy individual with a single cause of anemia, but in many cases the cause is not readily apparent and multiple conditions may be contributing.

Definitions

Anemia is defined for patient care as a reduction in one or more of the major red blood cell (RBC) measurements obtained as a part of the complete blood count (CBC):

• hemoglobin concentration
• hematocrit
• RBC count

A low hemoglobin concentration and/or low hematocrit are the parameters most widely used to diagnose anemia. The bone marrow produces red blood cells in response to erythropoietin produced by the kidney. Red blood cells transport oxygen and the percentage of oxygen is felt by the kidney which produces erythropoietin in order to maintain a stable level of red blood cell production.

Characteristics of Red Blood Cells

Red Blood Cells are:

• Erythrocytes
• Biconcave

discs

• Able to readily squeeze through capillaries
• Lack nuclei (anucleate) and mitochondria
• Average volume: 90-95 cubic micrometres
• Normal men: 520000 cubic mm
• Normal women: 470000 cubic mm
• Many function is to carry oxygen
• Essentially bags of hemoglobin: few organelles
• Outnumber with blood cells 1000:1
• Contain the plasma membrane protein spectrin and other proteins
• Major factor contributing to blood viscosity

1. Oxygen from lungs
2. Oxygen bonded to hemoglobin
3. Oxygen released to tissue cells

The main parameters are:

Hemoglobin

Is made by 4 chains (two alpha and two beta). It is the most informative parameter.

Hemoglobin is reported as the concentration of hemoglobin in whole blood. Values may be expressed as grams of hemoglobin per 100 mL (g/dL) or per liter (g/L).

Hematocrit

Hematocrit (HCT), also called packed cell volume (PCV), is the percentage of blood volume occupied by RBCs. It can be measured directly following centrifugation.

of a blood sample

When measured by an electronic cell counter, HCT is calculated from the RBC count (in millions/microL) and the mean corpuscular volume (MCV; in femtoliters [fL]):

HCT = ([RBC x MCV]/10)

RBC count

RBC count is the number of RBCs contained in a specified volume of whole blood, usually expressed as millions of cells per microL of whole blood.

World Health Organization (WHO) criteria for anemia in men and women are hemoglobin <13 and <12 g/dL, respectively.

However, these criteria were intended for use within the context of international nutrition studies and were not initially designed to serve as "gold standards" for diagnosing anemia.

Normal ranges for laboratory tests are defined as the range of values centered at the median that includes 95 percent of an apparently healthy population. For that reason, normal values of hemoglobin, HCT, and RBC count may differ depending on the population tested. Since hemoglobin is measured and hemoglobin is likely to be more

A study that used survey data to try to identify a lower normal hemoglobin in older individuals concluded that the World Health Organization (WHO) definitions are applicable in older adults. Thus, rather than seeking to define a lower limit for the reference range for older individuals as a population, it is preferable to focus on determining the appropriate evaluation of a low hemoglobin in each person and to individualize the approach to each person's circumstances, with an informed discussion and shared decision-making.

In individuals with anemia, hemoglobin and HCT decrease in parallel, although the HCT/hemoglobin ratio (approximately 3 in most cases) may vary according to the volume (size) of the cells. The RBC count also usually parallels the hemoglobin and HCT, except in cases of extreme microcytosis such as thalassemia, in which the RBC count may be increased despite the presence of anemia. The RBC count is less commonly used to diagnose anemia for this reason. A finding of high RBC

• Increased loss of blood volume or red cells
• Increased destruction of red cells (due to hereditary abnormalities of hemoglobin or to the presence of antibodies against RBC)
• Decreased production/differentiation of red cells due to: (to produce RBC is needed iron but also vitamins) nutritional deficiency: iron, vitamin B12, folate
• Chronic kidney disease (EPO deficiency)
• Miscellaneous causes (anemia of chronic diseases)

• Intense physical activity - Values in endurance athletes may vary significantly from those in other healthy individuals.
• Various

causes may contribute, including dilutional anemia from increased plasma volume, iron deficiency, and/or "march" hemolysis.

Pregnancy – During a healthy pregnancy, maternal red cell mass increases, but plasma volume increases to a greater degree, causing a relative decrease in hemoglobin and HCT. By the criterion of RBC mass, the individual is not anemic, but hemoglobin, HCT, and RBC count frequently decrease to anemic levels. The terms "physiologic" or "dilutional" anemia have been applied to this setting, although these individuals are not actually anemic and do not require evaluation as long as their hemoglobin remains ≥11g/dL in the first trimester, ≥10.5 g/dL in the second trimester, and ≥10.5 g/dL in the third trimester.

Older age – Values for hemoglobin and HCT in apparently healthy older adults are generally lower than those in younger adults, and differences between

males and females that are seen in younger adults are lessened with aging

Causes of higher values

Causes of higher values (may occasionally mask underlying anemia)

Smoking – Smoking causes an increase in hemoglobin, HCT, and RBC count due to increased levels of carbon monoxide, which reduces oxygen delivery. Thus, individuals who smoke or have significant exposure to secondary smoke or other sources of carbon monoxide may have HCT higher than normal.

Hemoconcentration – Individuals with dehydration or hypovolemia related to vomiting or diarrhea will have a relative increase in hemoglobin and HCT due to hemoconcentration. Anemia will become apparent after volume replacement. This is particularly a problem in patients with severe burns, in whom substantial RBC loss may be masked by exudative loss of plasma volume until fluid resuscitation has occurred.

High altitude – Persons living at high altitude have higher values than those living at sea level due to

1. relative hypoxiaRBC indices
2. Our nal goal is to determine the cause; so we have to do is to nd RBC indices
3. The red blood cell (RBC) indices describe RBC size, hemoglobin content, and uniformity of the RBC
4. These values can be very helpful in determining the cause of anemia.population. The mean corpuscular volume (MCV) and red cell distribution width (RDW) are generally the most useful.
5. MCV – Mean corpuscular volume (MCV) is the average volume (size) of the RBCs. It can be measured, as it is in automated cell counters, or calculated (MCV in femtoliters [fL] = 10 x HCT [in percent] ÷ RBC [in millions/microL]). RBCs with MCV in the normal range are roughly the same diameter as the nucleus of a normal lymphocyte on the peripheral blood smear.
6. Anemia can be classi ed based on whether the MCV is low, normal, or elevated.
7. MCH – Mean corpuscular hemoglobin (MCH) is the average hemoglobin content in a RBC. It is calculated (MCH in picograms [pg]/cell = hemoglobin [in g/dL]

MCH - Mean corpuscular hemoglobin (MCH) is the average amount of hemoglobin in each red blood cell (RBC). It is calculated as (MCH in picograms [pg] = hemoglobin [in grams] x 10 / RBC [in millions/microL]). A low MCH is typically reflected in an enlarged area of central pallor in RBCs on the peripheral blood smear (greater than one-third of the RBC diameter), which defines "hypochromia" on the blood smear. This may be seen in iron deficiency and thalassemia.

MCHC - Mean corpuscular hemoglobin concentration (MCHC) is the average hemoglobin concentration per RBC. It is calculated as (MCHC in grams [g]/dL = hemoglobin [in g/dL] x 100 / HCT [in percent]). Very low MCHC values are typical of iron deficiency anemia, and very high MCHC values typically reflect spherocytosis or RBC agglutination. Examination of the peripheral blood smear is helpful in distinguishing these findings.

RDW - Red cell distribution width (RDW) is a measure of the variation in RBC size, which is reflected in the degree of anisocytosis on the peripheral blood smear. RDW is calculated as the coefficient of variation (CV) of the red cell volume distribution.

(RDW = [standard deviation/MCV] x 100). A high RDW implies a large variation in RBC sizes, and a low RDW implies a more homogeneous population of RBCs. A high RDW can be seen in a number of anemias, including iron deficiency, vitamin B12 or folate deficiency, myelodysplastic syndrome (MDS), and hemoglobinopathies, as well as in patients with anemia who have received transfusions. Review of the peripheral blood smear often is helpful in identifying the cause.

Anisocytosis: Red blood cells of different shapes and dimensions.

Reticulocyte production Measurement

The reticulocyte is a stage in RBC development directly before the mature RBC. Reticulocytes are continually produced to replace RBCs that are cleared from the circulation (approximately 1 percent of RBCs are cleared per day). The reticulocyte count reflects the rate of RBC production.