Red Blood Cell Disorders Part 1

Red Blood Cell Disorders:

 Can be classified as either polycythemia or anemia.

 These disorders result from an imbalance in marrow multipotential or unipotential stem cell
production and maturation.

Polycythemia (Erythrocytosis):
 There is an increase concentration of RBCs, therefore have an increase Hct in the blood that is
above and normal for age and sex.
 Men= > 53% and female = > 51 %

Clinical Symptoms:
 Ruddy complexion
 Headaches
 Dizziness

Types of Polycythemia:
1. Relative polycythemia or pseudopolycythemia
 Refers to a condition in which the total red cell mass is normal but the red cell count or
hematocrit is elevated because the plasma volume is decreased.
 Cause of acute cases: Dehydration due to episodes of vomiting, diarrhea, profuse
sweating or burns
 Cause of Chronic cases: (Spurious Polycythemia or Gaisbock’s syndrome, Stress
Polycythemia)
 Almost all are men, have a high incidence of tobacco smoking and tend to be
obese and to have hypertension
 Laboratory Evaluation:
 RBC mass: Normal
 RBC count: Slightly increased
 Hgb and Hct: Slightly increased

2. Absolute polycythemia
 Refers to a true increase in the total red cell mass or erythrocytosis in the body
 Laboratory evaluation:
 RBC mass: Increased
 RBC count: Increased
 Hgb, Hct : Increased

A. Primary absolute polycythemia or Polycythemia vera (panmyelosis)

Synonyms: True polycythemia,
Osler’s disease,
Erythremia,
Primary polycythemia
Vaquez-Osler disease
Splenomegaly polycythemia

Cause: Unknown

MTE-116 Hematology 1 Donna Therese M Taguinod, RMT, MPH

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 Additional laboratory Findings:

◦ Erythropoietin level: Normal to decreased
◦ Wbc count: Increased (leukocytosis)
◦ Platelet count : Increased (thrombocytosis)

B. Secondary Absolute Polycythemia (increased erythropoietin)

Causes:
a. Appropriate erythropoietin production; hypoxia
1. Arterial oxygen unsaturation: Physiologic response to systemic
hypoxia
i. high altitude (decrease O2)
ii. pulmonary disease (COPD)
iii. cyanotic heart disease
iv. smoker’s polycythemia
v. methemoglobinemia
vi. Hb M
vii. Massive obesity
2. High oxygen affinity hemoglobinopathy (familial polycythemia)
b. Inappropriate erythropoietin production
1. Neoplasm
i. Renal carcinoma
ii. Cerebellar hemangioma
iii. Hepatoma
iv. Uterine fibroids
v. Adrenal cortical neoplasms
2. Renal pathology
i. Cysts
ii. Hydronephrosis
iii. transplantation

c. Familial polycythemia

Additional Laboratory Evaluation:

1. EPO level: Normal to Increased
2. WBC count: Normal
3. Platelet Count : Normal

MTE-116 Hematology 1 Donna Therese M Taguinod, RMT, MPH

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ANEMIA:
1. Anemia is considered to be present if the hemoglobin concentration of the red blood cells
(RBCs) or the packed cell volume of RBCs (hematocrit) is below the lower limit of the 95%
reference interval for the individual’s age, gender, and geographical location.
2. Anemia is physiologically defined as a condition in which the circulating blood lacks the ability to
adequately oxygenate body tissues. Anemia may be a sign of an underlying disorder.
a. Dilutional anemia with normal or increased total red cell mass may occur with
pregnancy, macroglobulinemia, and splenomegaly.
b. Some anemias have more than one pathogenetic mechanism and go through more than
one morphological state, such as blood loss anemia. In the case of accelerated red cell
destruction, hemolysis in excess of the ability of the marrow to replace these losses
occurs.

Clinical features of anemia:

Major Adaptations:
1. Cardiovascular system (with increased stroke volume and tachycardia)
2. Hemoglobin 02 dissociation curve.

The presence or absence of clinical features can be considered under four major headings:
1. Speed of onset: Rapidly progressive anemia causes more symptoms than anemia of slow onset
because there is less time for adaptation in the cardiovascular system and in the 02 dissociation
curve hemoglobin
2. Severity: Mild anemia often produces no symptoms or signs but these are usually present when
the hemoglobin is less than 9-10 g/dL
3. Age: The elderly tolerate anemia less well than the young because of the effect of lack of oxygen
on organs when normal cardiovascular compensation (increased cardiac output caused by
increased stroke volume and tachycardia) is impaired.
4. Hemoglobin 02 dissociation curve: This adaptation is particularly marked in some anemia which
either affect red cell metabolism directly (e.g. the anemia of pyruvate kinase deficiency which
causes a rise in 2,3-DPG concentration in the red cells) or which are associated with a low
affinity hemoglobin (e.g. Hb S).

Signs
General signs:
1. Pallor of mucous membranes which occurs if the hemoglobin level is less than 9 - 10 g/dL.
Conversely, skin color is not a reliable sign.
2. A hyperdynamic circulation may be present with tachycardia, a bounding pulse, cardiomegaly
and a systolic flow murmur especially at the apex. Particularly in the elderly, features of
congestive heart failure may be present. Retinal hemorrhages are unusual.

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Specific signs are associated with particular types of anemia:

1. Koilonychia ’spoonnails’ with iron deficiency
2. Jaundice with hemolytic or megaloblastic anemia
3. Leg ulcers with sickle cell and other hemolytic anemia
4. Bone deformities with thalassemia major and other severe congenital hemolytic anemia

Symptoms
1. Shortness of breath particularly on exercise
2. Weakness
3. Lethargy
4. Palpitation
5. Headaches

In older subjects:
1. Cardiac failure
2. Angina pectoris or intermittent claudication or confusion may be present
3. Visual disturbances because of retinal hemorrhages may complicate very severe anemia,
particularly of rapid onset

Diagnosis of Anemia:
1. Clinical history
2. Physical signs such as pallor, fatigue, weakness and shortness of breath
3. Laboratory Tests

CLASSIFICATIONS OF ANEMIA
1. Red cell morphology, which was originally proposed by Wintrobe, categorizes anemia by the
size of the erythrocytes. The major limitation of such a classification is that it tells nothing about
the etiology or reason for the anemia.

Microcytic, hypochromic Normocytic, normochromic Macrocytic

MVC <80 fL MCV 80-100 fL MCV >100 fL
MCH <26 pg MCH 26–32 pg MCH > 32 pg
 Iron Deficiency  Many hemolytic anemia  Megaloblastic: Vitamin
 Thalassemia  Anemia of Chronic disease B12 or folate deficiency
 Anemia of Chronic disease (some cases)  Non-megaloblastic:
(some cases)  After acute blood loss alcohol, liver disease,
 Lead poisoning  Renal Disease myelodysplasia, aplastic
 Sideroblastic anemia  Mixed deficiencies anemia, etc.
 Bone marrow failure (post-
chemotherapy, infiltration
by carcinoma, etc.)

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2. Pathophysiological
Three major categories:
1. Blood loss: Acute or Chronic
2. Impaired red cell production
a. Aplastic
b. Iron deficiency
c. Sideroblastic Anemia
d. Anemia of chronic disease
e. Megabloblastic
3. Hemolytic –Accelerated red cell destruction (hemolysis in excess of the ability of the
marrow to replace these losses)
a. Inherited defects
b. Acquired defects
c. Hemoglobin Disorders

LABORATORY ASSESSMENT OF ANEMIAS:

1. Complete Blood Count:

Quantitative Measurements of Anemia

The three major laboratory manifestations of anemia include:
a. A decreased hemoglobin concentration
Normal Values: Males : 14-18 g/dL
Females: 12-16 g/dL
Moderate anemia: 7-10 g/dL
Severe anemia: <7 g/dL

b. A reduced packed cell volume (microhematocrit) level

Normal Values: Males : 42-52%
Females: 37-47%

c. A decreased erythrocyte concentration

Normal Values: Males: 4.7 to 6.1 x 1012/L
Females: 4.2 to 5.4 x 1012/L

Other quantitative measurements of erythrocytes:

a. The red cell histogram
b. Red cell distribution width (RDW) or red cell morphology index (RCMI)
 A mathematical calculation that gives insight into the amount of anisocytosis
(variation in size)
 The RDW is derived as follows = (Standard deviation of RBC volume/mean MCV) X
100
Normal Values: 11.5 to 14.5%
MTE-116 Hematology 1 Donna Therese M Taguinod, RMT, MPH
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c. RBC indices:
1. MCV - Indicates the average size (volume) of the red cells
2. MCH - A measurement of the hgb content in RBC’s
3. MCHC – A measure of the concentration of hgb in the average RBC

Normal Values:
MCV = 80 to 100 fL
MCH = 26 to 32 pg
MCHC = 32 to 36 % (320 g/L to 360 g/L)

2. Examination of blood smear

a. Alteration in size (Anisocytosis)
b. Alteration in shape (Poikilocytosis)
c. An RBC with normal hgb content will appear normochromic (MCHC= 32-36)
d. An RBC with decreased hgb content will appear hypochromic (MCHC= <32)
e. RBC size is designated as microcytic (MCV= <80), normochromic (MCV= 80-
100) or macrocytic (MCV= >100)

3. Reticulocyte
 Reticulocytes are nonnucleated RBCs and that contain remnant RNA material,
reticulum
 Useful in determining the response to the anemia and the potential on the BM to
manufacture RBC’s. Expressed as a percentage of RBC’s.
 Reticulum cannot be visualized by Wright’s stain. To be counted and evaluated,
reticulocytes must be stained with supravital stains, like new methylene blue or
brilliant cresyl blue.
 On Wright’s stain, reticulocytes are seen as polychromatophilic
macrocytes, or large, bluish cells. The term used for retics on Wright’s
stain is polychromasia.

% retics (uncorrected) = # of retics counted x 100

1000

Normal Values: Adult: 0.5% to 1.5 %

Newborn: 2.0% to 6.0%

 When anemia is present, it is useful to correct the retic using the patient’s hct in
order to assess the appropriate BM response.
Corrected retic (%) = % retic x Patient hct
Normal HCT*
*Normal male hematocrit = 45%

 The normal value based on correction for anemia is the same as the previously
stated normal reticulocyte values of 0.5% to 2.0%

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 Prematurely released retics (stress reticulocytes) remain in the blood and take from ½ to
1 ½ days longer to mature. This will cause even the “corrected” retic to be elevated, so
calculation must be performed to correct this situation to obtain the reticulocyte
production index. The rationale for obtaining this value is that the life span of the
circulating stress reticulocytes is 2 days instead of the normal 1 day. A maturation time
table* is used for this calculation.
RPI = corrected retic
Maturation time* in days

Hematocrit (%) Maturation Time (Days)

45 1.0

35 1.5

25 2.0

15 2.5

4. Bone Marrow Examination

 Total erythropoiesis is assessed from the marrow cellularity and the myeloid: erythroid
(M:E) ratio.
 The M:E ratio is calculated by dividing the total number of granulocytes and their
precursors by the total number of nucleated RBCs.
ME ratio = Total # gran and their precursors
Total # of nRBC
Normal range: 2:1 to 4:1

 The Marrow Cellularity is evaluated by the fat cell to nucleated hematopoietic cell
ratio
 This ratio falls and may be reversed when total erythropoiesis is selectively
increased.
5. Red cell survival Time
 This used to be measured by 51Cr-labelled red cell survival
6. EPO level
7. Iron Studies ( iron, TIBC, ferritin)
8. RBC Inclusions are seen on Wright-stained smears in certain anemia

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Supplementary Assessment of Anemias

1. Hemoglobin electrophoresis
2. Sickle cell testing
3. Glucose-6-phosphate dehydrogenase (G6PD) assay
4. Fetal hemoglobin (Hb F) concentration
5. Malarial smears
6. Leukocyte and platelet counts measurement of these helps to distinguish “pure” anemia from
“pancytopenia” (a drop in red cells, granulocytes and platelets) which suggests a more general
marrow defect (e.g. caused by marrow hypoplasia or infiltration) or general destruction of cells
(e.g. hypersplenism).

MTE-116 Hematology 1 Donna Therese M Taguinod, RMT, MPH

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