Anemias: red blood cell morphology and approach to diagnosis jaundice, and various underlying disease.

CHAPTER 19
- iron deficiency can lead to an interesting symptom called pica
- The term anemia is derived from the Greek word anaimia, meaning - Patients with pica have cravings for unusual substances such as
“without blood ice (pagophagia), cornstarch, or clay.
-decrease in hemoglobin concentration or number of RBCs results in
decreased oxygen delivery to tissue, resulting in tissue hypoxia -Certain features should be evaluated closely during the physical
- affecting 1.62 billion worldwide. examination to provide clues to hematologic disorders, such as
skin (for petechiae), eyes (for pallor, jaundice, and hemorrhage), and
mouth (for mucosal bleeding)

- functional definition of anemia is a decrease in the oxygen carrying - . The examination should also search for sternal tenderness,
capacity of the blood. lymphadenopathy, cardiac murmurs, splenomegaly, and
- arise when there’ insufficient hemoglobin or the hemoglobin has hepatomegaly.
impaired function.
- Jaundice is important for the assessment of anemia, because it
-Anemia is defined operationally as a reduction in the hemoglobin may be due to increased RBC destruction.
content of blood that can be caused by a decrease in RBCs,
hemoglobin, and hematocrit below the reference interval for healthy - rapid fall in hemoglobin concentration typically have tachycardia
individuals of similar age, sex, and race, under similar environmental (fast heart rate)
condition. - Moderate anemias (hemoglobin concentration of 7 to 10 g/dL) ,
- race, environmental, and laboratory factors can also influence the may cause pallor of conjunctivae and nail beds but may not produce
values the reference interval. clinical symptoms if the onset of anemia is slow.

- Severe anemias (hemoglobin concentration of less than 7 g/dL),

usually produce tachycardia, hypotension, and other symptoms of
- A decrease in oxygen delivery to tissues decreases the energy volume loss
available to individuals to perform day-to-day activities.
- classic symptoms associated with anemia, fatigue and shortness of -Severity of the anemia is gauged by the degree of reduction in
breath. hemoglobin, cardiopulmonary adaptation, and the rapidity of
- questioning the patient, particularly with regard to diet, drug progression of the anemia.
ingestion, exposure to chemicals, occupation, hobbies, travel,
bleeding history, race or ethnic group, family history of disease,
neurologic symptoms, previous medication, previous episodes of
 defective precursors often undergo apoptosis (programmed cell
- Anemia resulting from acute blood loss, such as with severe death) in the bone marrow before they have a chance to mature to
hemorrhage. the reticulocyte stage and be released into the peripheral circulation.
- adequate perfusion of vital organs and maintenance of
homeostasis.
-megaloblastic anemia (deficient DNA synthesis due to vitamin B12
-In cases of severe blood loss, such as in trauma, blood volume or folate deficiency), thalassemia (deficient globin chain synthesis),
decreases and hypotension develops, resulting in decreased blood and sideroblastic anemia (deficient protoporphyrin synthesis).
supply to the brain and heart, immediate adaptation, there is
sympathetic overdrive that results in increasing heart rate, -the peripheral blood hemoglobin is low, which triggers an increase
respiratory rate, and cardiac output. in erythropoietin leading to increased erythropoietic activity. Although
the RBC production rate is high, it is ineffective in that many of the
- severe anemia, blood is preferentially shunted to organs that are defective RBC precursors undergo destruction in the bone marrow
key to survival, including the brain, muscle, and heart- his results in
oxygen being preferentially supplied to vital organs even in the
presence of reduced oxygen-carrying capacity.

- tissue hypoxia triggers an increase in RBC 2,3-

bisphosphoglycerate that shifts the oxygen dissociation curve to the END RESULT IS A DECREASED NUMBER OF CIRCULATING
right (decreased oxygen affinity of hemoglobin) and results in RBCS RESULTING IN ANEMIA.
increased delivery of oxygen to tissues.

-Persistent Anemia, the body develops physiologic adaptations to -Insufficient Erythropoiesis refers to a decrease in the number of
increase the oxygen-carrying capacity of a reduced amount of erythroid precursors in the bone marrow, resulting in decreased RBC
hemoglobin, which improves oxygen delivery to tissue. With production and anemia - can lead to the decreased RBC production,
persistent, bone marrow is able to produce functional RBCs that including a deficiency of iron (inadequate intake, malabsorption,
replace the daily loss of RBCs. excessive loss from chronic bleeding); a deficiency of erythropoietin
(renal disease); or loss of the erythroid precursors due to an
-Chronic Anemias that enables patients with low levels of autoimmune reaction (aplastic anemia, acquired pure red cell
hemoglobin to remain relatively asymptomatic. aplasia) or infection (parvovirus B19). Infiltration of the bone marrow
with granulomas (sarcoidosis) or malignant cells (acute leukemia)
-Ineffective Erythropoiesis refers to the production of erythroid can also suppress erythropoiesis.
precursor cells that are defective.
 - A reticulocyte count should be performed for every patient with
anemia. As with RBCs, automated analyzers provide accurate
measurements of reticulocyte counts.

Anemia can also develop as a result of acute blood loss (such as a - The RBC histogram provided by the automated analyzer is an RBC
traumatic injury) or chronic blood loss (such as an intermittently volume frequency distribution curve with the relative number of cells
bleeding colonic polyp. plotted on the ordinate and RBC volume (fL) on the abscissa. In
healthy individuals, the distribution is approximately Gaussian.
Increased hemolysis results in a shortened RBC life span, thus Abnormalities include a shift in the curve to the left (population of
increasing the risk for anemia. smaller cells or microcytosis) or to the right (larger cell population or
- Chronic blood loss induces iron deficiency as a cause of anemia. macrocytosis). A widening of the curve caused by a greater variation
With acute blood loss and excessive hemolysis, the bone marrow of RBC volume about the mean can occur due to a population of
takes a few days to increase production of RBCs. RBCs with different volumes (anisocytosis).
-This response may be inadequate to compensate for a sudden
excessive RBC loss as in traumatic hemorrhage or in conditions with
a high rate of hemolysis and shortened RBC survival. -increased RDW correlates with anisocytosis on the peripheral blood
-causes of hemolysis exist, including intrinsic defects in the RBC film.
membrane, enzyme systems, or hemoglobin, or extrinsic causes
such as antibody-mediated processes, mechanical fragmentation, or -. Automated analyzers calculate the RDW by dividing the
infection-related destruction. standard deviation of the RBC volume by the MCV and then
multiplying by 100 to convert to a percentage.

RETICULOCYTE COUNT

-reticulocyte count serves as an important tool to assess the bone

marrow’s ability to increase RBC production in response to an
To detect the presence of anemia the medical laboratory anemia
professional performs a complete blood count (CBC) using an -Reticulocytes are young RBCs that lack a nucleus but still contain
automated hematology analyzer to determine the RBC count, residual ribonucleic acid (RNA) to complete the production of
hemoglobin concentration, hematocrit, RBC indices, white blood cell hemoglobin.
count, and platelet count. -circulate peripherally for only 1 day while completing their
development.
-RBC indices include the mean cell volume (MCV), mean cell
hemoglobin (MCH), and mean cell hemoglobin concentration
(MCHC) -adult reference interval for the reticulocyte count is 0.5% to 2.5%
- newborn reference interval is 1.5% to 6.0% - values change to
approximately those of an adult within a few weeks after birth. - Chronic blood loss, on the other hand, does not lead to an
appropriate increase in the reticulocyte count, but rather leads to iron
- The reference interval for the absolute reticulocyte count is 20 to deficiency and a subsequent low reticulocyte count. Thus an
115 3 109/L, based on an adult RBC count within the reference inappropriately low reticulocyte count results from decreased
interval. production of normal RBCs, due to either insufficient or ineffective
- severe anemia may seem to be producing increased numbers of erythropoiesis.
reticulocytes; For example, an adult patient with 1.5 3 1012/L RBCs -
and 3% reticulocytes has an absolute reticulocyte count of 45 3
109/L.
- to obtain a better representation of RBC production. First, to obtain
a corrected reticulocyte count, one corrects for the degree of anemia
by multiplying the reticulocyte percentage by the patient’s hematocrit
and dividing the result by 45 (the average normal hematocrit).

-If the reticulocytes are released prematurely from the bone marrow
and remain in the circulation 2 to 3 days (instead of 1 day), the
corrected reticulocyte count must be divided by maturation time to
determine the reticulocyte production index (RPI).

state-of-the-art automated hematology analyzers determine the PERIPHERAL BLOOD FILM EXAMINATION
fraction of immature reticulocytes among the total circulating
reticulocytes, called the immature reticulocyte fraction (IRF). The IRF important component in the evaluation of an anemia is examination
is helpful in assessing early bone marrow response after treatment of the peripheral blood film, with particular attention to RBC diameter,
for anemia. shape, color, and inclusions.
-Also serves as a quality control to verify the results produced by
- determining whether an anemia is due to an RBC production defect automated analyzer
or to premature hemolysis and shortened survival defect. If there is -Normal RBCs on a Wright-stained blood film are nearly uniform,
shortened RBC survival, as in the hemolytic anemias, the bone ranging from 6 to 8 mm in diameter.
marrow tries to compensate by increasing RBC production to release - Small or microcytic cells are less than 6 mm in diameter
more reticulocytes into the peripheral circulation. - large or macrocytic RBCs are greater than 8 mm in diameter
-an increased reticulocyte count is a hallmark of the hemolytic - Certain shape abnormalities of diagnostic value (such as sickle
anemias, can be observed over time in acute blood loss.
cells, spherocyte Certain shape abnormalities of diagnostic value
(such as sickle cells, spherocyte.
- review of the white blood cells and platelets may help show that a
more generalized bone marrow problem is leading to the anemia:
For example, hypersegmented neutrophils can be seen in vitamin
B12 or folate deficiency, whereas blast cells and decreased platelets
may be an indication of acute leukemia.
 -approach to the patient with anemia begins with taking a complete history and
performing a physical examination.

MORPHOLOGIC CLASSIFICATION OF ANEMIA BASED ON

MEAN CELL VOLUME OR MCV
*Microcytic anemia- is characterized by an emcee of less than 80 fL. With small
rbc less than 6úm in diameter. often associated with a high chromia characterized
BONE MARROW EXAMINATION by an increase and power of the RBC and an MCHC of less than 32 g/dL. Caused
by condition that results in HgB synthesis.
-The cause of many animals can be determined from the history physical
*heme synthesis - diminished in iron deficiency iron sequestration or chronic
examination and result of laboratory tests on peripheral blood.
inflammatory states and defective protoporphyrin synthesis or sideroblastic
BIOPSY/ BONE MARROW ASPIRATION - may help in stablish a ng the cause of anemia, lead poisoning.
anemia.
Note: iron deficiency is the most common cause of microcytic anemia the low
BONE MARROW EXAMINATION- evaluates hematopoiesis and can determine if iron level is insufficient for maintaining normal erythropoiesis.
there is an infiltration of abnormal cells into the bone marrow. Important findings
in the bone marrow that can point to the underlying cause of anemia include
abnormal cellularity example hypocelllularity in aplastic anemia. *Macrocytic Anemia- is characterized by an MCV greater than 100fL. With large
RBC with diameter of greater than 8úm. Macrocytic anemias arise from condition
OTHER LABORATORY TEST that result in megaloblastic or non megaloblastic red cell development in the
bone marrow.
*Routine Urinalysis - detect hemoglobinuria or an increase in urobilinogen with a
microscopic examination to detect hematuria or hemosiderin. Note: Megaloblastic anemias- caused by condition that impairs synthesis of
deoxyribonucleic acid or dna such as vitamin b12 and folate deficiency or
*Examination of stool- to detect of occult blood or intestinal parasites.
myelodysplasia.
* Haptoglobin/lactate dehydrogenase/ unconjugated bilirubin- to detect
excessive hemolysis.
*Non megaloblastic anemias- are typically related to membrane changes owing
Note: after hematologic a laboratory studies are completed the anemia may be
to destruction of the cholesterol to phospholipid ratio.
classified based on reticulocyte count MCV and peripheral blood film findings.
Remember: Macrocytic anemias- often seem in patient with chronic liver disease.
APPROACH TO EVALUATING ANIMIAS
*Normocytic anemia- characterized by an MCV rangees 80-100fL.
MORPHOLOGIC CLASSIFICATION OF ANEMIAS AND
RETICULOCYTE COUNTS.
• Inffective RBC production- decreased reticulocyte count.
• Excessive RBC loss- increased reticulocyte counts.

-MCV can be further categorize into 3 groups;

• Normocytic
• Microcytic
• Macrocytic

MORPHOLOGIC CLASSIFICATION AND THE RED BLOOD CELL

DESTRIBUTION WIDTH
- Each of the MCV classification mentioned can be subclassified into;
• Homogenous- normal RDW
• Heterogenous- increased/high RDW.

Note: decreased MCV and increased RDW is an indication of IRON DEFICIENCY.