3. RETICULOCYTES
Reticulocytes are premature red blood cells,
typically composing about 1% of the red cells in the
human body.
Reticulocytes develop and mature in the red bone
marrow and then circulate for about a day in the
blood stream before developing into mature red
blood cells.
Like mature red blood cells, reticulocytes do not
have a cell nucleus. They are called reticulocytes
because of a reticular (mesh-like) network of
ribosomal RNA that becomes visible under a
microscope with certain stains such as new
methylene blue.
4.
5.
6.
7. Remember that the bonemarrow has
the capacity to increase RBC
production 5-10 times the normal
production.
Thus, if all necessary raw products are
available, the RBC life span can decrease
to about 18 days before bone marrow
compensation is inadequate and anemia
develops.
8. RBC “rule of 3’s”
For normal erythrocytes:
hemoglobin (g/dL)
hematocrit (%)
3 x RBC count (millions)
3 x hemoblobin (g/dL)
3%
Failure to obey this “rule of 3’s” suggests an
abnormality in erythrocytes (sickle cells, etc)
9. Normal range :
In male : 5 - 6 millions/cmm of blood
In female :4 – 5 millions/cmm of blood
Decrease in Hemoglobin concentration
Normal range :
In male : 15 -18 gm/100ml of blood
In female : 12 – 15 gm/100ml of blood
10. Introduction
In its broadest sense, anemia is a functional
inability of the blood to supply the tissue with
adequate O2 for proper metabolic function.
Anemia is not a disease, but rather the
expression of an underlying disorder or
disease.
12. Magnitude of Problem
Globally, is about 30 %
In developing countries &
India, incidence is around
40 – 90%.
Responsible for 40% of
maternal deaths in third world
countries.
Important cause of direct and
indirect maternal deaths
- Vitere FE Adv Exp Med Biol 1994;352:127
13.
Anemia is a common condition.
It occurs in all age groups and all racial and ethnic groups.
Both men and women can have anemia, but women of
childbearing age are at higher risk for the condition.
This is because women in this age range lose blood from
menstruation.
Researchers continue to study how anemia affects older adults.
More than 10 percent of older adults have mild forms of anemia.
Many of these people have other medical conditions as well.
14. Definition
Anemia - insufficient Hb to carry out O2 requirement
by tissues.
WHO definition : Hb conc.
11 gm %
For developing countries : cut off level suggested is
10 gm %
- WHO technical report Series no. 405, Geneva 1968
Centre for disease control, MMWR 1989;38:400-4
22. ANEMIA
Pathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
a. intrinsic abnormality
b. extrinsic abnormality
II ↓RBC production
1. stem cell abnormality
2. erythroblast abnormality
3. unknown/multiple mechanism
31. The Three Causes of Anemia
Decreased red blood cell
production
Increased red blood cell
destruction
Red blood cell loss
32. Decreased RBC production
Lack of iron, B12, folate
Marrow is dysfunctional from myelodysplasia, tumor
infiltration, aplastic anemia, etc.
Bone marrow is suppressed by chemotherapy or
radiation
Low levels of erythropoeitin, thyroid hormone, or
androgens
33. Increased RBC destruction
RBCs live about 100 days
Acquired: autoimmune hemolytic anemia, TTP-HUS,
DIC, malaria
Inherited: spherocytosis, sickle cell, thalassemia
39. ASSESSMENT
– Patient history
– Patient physical exam
– Signs and symptoms exhibited by the patient
– Hematologic lab findings
Identification of the cause of anemia is
important so that appropriate therapy is
used to treat the anemia.
40. Before making a diagnosis of anemia,
one must consider:
Age
Sex
Geographic location
Presence or absence of lung disease
41. DIAGNOSIS OF ANEMIA
How does one make a clinical diagnosis
of anemia?
Patient history
– Dietary habits
– Medication
– Possible exposure to chemicals and/or toxins
– Description and duration of symptoms
42. DIAGNOSIS OF ANEMIA
• Tiredness
• Muscle fatigue and weakness
• Headache and vertigo (dizziness)
• Dyspnia (difficult or labored breathing) from
exertion
• G I problems
• Overt signs of blood loss such as hematuria
(blood in urine) or black stools
43. Physical examination
–General findings might include
• Hepato or splenomegaly
• Heart abnormalities
• Skin pallor
–Specific findings may help to establish
the underlying cause:
• In vitamin B12 deficiency there may be signs
of malnutrition and neurological changes
• In iron deficiency there may be severe pallor,
a smooth tongue, and esophageal webs
• In hemolytic anemias there may be jaundice
due to the increased levels of bilirubin from
increased RBC destruction
44. Laboratory investigation
A complete blood count, CBC, will
include:
–An RBC count:
• At birth the normal range is 3.9-5.9 x 106/ul
(1012/L)
• The normal range for males is 4.5-5.9 x 106/ul
• The normal range for females is 3.8-5.2 x
106/ul
• Note that the normal ranges may vary slightly
depending upon the patient population.
45. DIAGNOSIS OF ANEMIA
–Hematocrit (Hct) or packed cell volume in
% or (L/L)
• At birth the normal range is 42-60% (.42.60)
• The normal range for males is 41-53%
(.41-.53)
• The normal range for females is 38-46%
(.38-.46)
• Note that the normal ranges may vary slightly
depending upon the patient population.
46. DIAGNOSIS OF ANEMIA
–Hemoglobin concentration in
grams/deciliter - the RBCs are lysed and
the hemoglobin is measured
spectrophotometrically
• At birth the normal range is 13.5-20 g/dl
• The normal range for males is 13.5-17.5 g/dl
• The normal range for females is 12-16 g/dl
• Note that the normal ranges may vary slightly
depending upon the patient population.
–RBC indices – these utilize results of the
RBC count, hematocrit, and hemoglobin
to calculate 4 parameters:
47. DIAGNOSIS OF ANEMIA
• Mean corpuscular volume (MCV) – is the
average volume/RBC in femtoliters (10-15 L)
• Hct (in %)/RBC (x 1012/L) x 10
• At birth the normal range is 98-123
• In adults the normal range is 80-100
• The MCV is used to classify RBCs as:
• Normocytic (80-100)
• Microcytic (<80)
• Macrocytic (>100)
48. DIAGNOSIS OF ANEMIA
•Mean corpuscular hemoglobin
concentration (MCHC) – is the
average concentration of
hemoglobin in g/dl (or %)
• Hgb (in g/dl)/Hct (in %) x 100
• At birth the normal range is 30-36
• In adults the normal range is 31-37
• The MVHC is used to classify RBCs as:
• Normochromic (31-37)
• Hypochromic (<31)
• Some RBCs are called hyperchromic
49. DIAGNOSIS OF ANEMIA
• Mean corpuscular hemoglobin (MCH) –
is the average weight of
hemoglobin/cell in picograms (pg= 1012 g)
• Hgb (in g/dl)/RBC(x 1012/L) x 10
• At birth the normal range is 31-37
• In adults the normal range is 26-34
• This is not used much anymore because it
does not take into account the size of the
cell.
50. DIAGNOSIS OF ANEMIA
• Red cell distribution width (RDW) – is
a measurement of the variation in RBC
cell size
• Standard deviation/mean MCV x 100
• The range for normal values is 11.5-14.5%
• A value > 14.5 means that there is
increased variation in cell size above the
normal amount (anisocytosis)
• A value < 11.5 means that the RBC
population is more uniform in size than
normal.
52. DIAGNOSIS OF ANEMIA
–Reticulocyte count gives an
indication of the level of the bone
marrow activity.
• Done by staining a peripheral blood
smear with new methylene blue to help
visualize remaining ribosomes and ER.
The number of reticulocytes/1000 RBC
is counted and reported as a %.
53. DIAGNOSIS OF ANEMIA
• At birth the normal range is 1.8-8%
• The normal range in an adult (i.e. in
an individual with no anemia) is .51.5%. Note that this % is not normal
for anemia where the bone marrow
should be working harder and
throwing out more reticulocytes per
day. In anemia the reticulocyte
count should be elevated above the
normal values.
55. DIAGNOSIS OF ANEMIA
–Blood smear examination . The
smear should be evaluated for the
following:
• Poikilocytosis – describes a variation
in the shape of the RBCs. It is normal
to have some variation in shape, but
some shapes are characteristic of a
hematologic disorder or malignancy.
58. DIAGNOSIS OF ANEMIA
•Erythrocyte inclusions – the RBCs in the
peripheral smear should also be examined
for the presence of inclusions or a variation
in erythrocyte distribution :
59.
60. DIAGNOSIS OF ANEMIA
•A variation in size should be
noted (anisocytosis) and cells
should be classified as
•Normocytic
•Microcytic
•Macrocytic
•A variation in hemoglobin
concentration (color) should be
noted and the cells should be
62. DIAGNOSIS OF ANEMIA
•The peripheral smear should also
be examined for abnormalities in
leukocytes or platlets.
•Some nutritional deficiencies,
stem cell disorders, and bone
marrow abnormalities will also
effect production, function,
and/or morphology of platlets
and/or granulocytes.
•Finding abnormalities in the
63. •In a bone marrow sample, the
following things should be noted:
•
•
•
•
•
•
Maturation of RBC and WBC series
Ratio of myeloid to erythroid series
Abundance of iron stores (ringed sideroblasts)
Presence or absence of granulomas or tumor cells
Red to yellow ratio
Presence of megakaryocytes
– Hemoglobin electrophoresis – can be used to identify the
presence of an abnormal hemoglobin (called
hemoglobinopathies). Different hgbs will move to
different regions of the gel and the type of hemoglobin
may be identified by its position on the gel after
electrophoresis.
64. DIAGNOSIS OF ANEMIA
– Evaluation of RBC enzymes and metabolic pathways –
enzyme deficiencies in carbohydrate metabolic pathways
are usually associated with a hemolytic anemia.
– Evaluation of erythropoietin levels – is used to determine
if a proper bone marrow response is occurring.
•Low levels of RBCs could be due
to a bone marrow problem or to a
lack of erythropoietin production.
– Serum iron, iron binding capacity and % saturation –
used to diagnose iron deficiency anemias (more on this
later)
– Bone marrow cultures – used to determine the viability of
stem cells.
65. Management Options
Pre – pregnancy :
Treat the cause before conception
Pre-pregnancy balanced diet, education
and health support.
Build up iron stores during adolescent
phase
67. Oral Iron Therapy
Ideal dose – 100mg per day (prophylactic)
Ferrous gluconate, ferrous fumarate, ferrous
succinate, ferrous sulphate, ferrous ascorbate citrate
Rise in Hb – 0.8 gm / dl / week
Side effects -G I upset most common
Pt. compliance not guaranteed
Ineffective in pts with worm infestations
Inconclusive evidence on benefit of controlled release
Iron preparation
68. Absorption of Ferrous Salts
Uncontrolled Passive Absorption
Iron salts are dissociated into bivalent or trivalent iron salts
Diffuses as free iron ions through the upper part of the
gastrointestinal mucosa
Taken up by transferrin and incorporated into ferritin.
For binding to ferritin and transferrin ferrous iron has to be
converted into ferric iron by oxidation
Highly reactive free radicals are produced during this process
All ionic iron including carbonyl iron are absorbed similarly
•
Borbolla JR. Cicero RE, Dibilox MM, Sotres RD et al.. Rev Mex Pediatr 2000; 67(2): 63-67
•
Heubers KA, Brittenham GM, Csiba E, Finch CA. J Lab Clin Med 1986 ; 108 ; 473-8.
69. Parenteral Therapy :
Traditional Indications
Intolerance to oral iron
Poor compliance to oral iron
Gastrointestinal disorders
Malabsorption syndromes
Rapid blood loss
70. Parenteral Therapy :
Traditional Indications
Inability to maintain iron balance
(haemodialysis)
Patient donating large amount of blood
for auto-transfusion programme
? Pregnant women with severe IDA,
presenting late in pregnancy
72. PREVENTION
Some common forms of anemia are most easily prevented by eating a healthy diet
and limiting alcohol use. All types of anemia are best avoided by seeing a doctor regularly
and when problems arise. In the elderly, routine blood work ordered by the doctor, even if
there are no symptoms, may detect anemia and prompt the doctor to look for the underlying
causes.
73.
74. SUMMARY
Preventing anemia and having the correct number of red blood
cells requires cooperation among the kidneys, the bone marrow, and
nutrients within the body. If the kidneys or bone marrow are not
functioning, or the body is poorly nourished, then normal red blood cell
count and function may be difficult to maintain.
Anemia is actually a sign of a disease process rather than a
disease itself. It is usually classified as either chronic or acute. Chronic
anemia occurs over a long period of time. Acute anemia occurs quickly.
Determining whether anemia has been present for a long time or whether
it is something new, assists doctors in finding the cause. This also helps
predict how severe the symptoms of anemia may be.
75. Take Home Message
Anaemia although preventable is a global problem
Anaemia still is the commonest cause of maternal mortality
and morbidity in spite of easy diagnosis and treatment
Anaemia can be due to a number of causes,
including certain diseases or a shortage of iron, folic
acid or Vitamin B12.
The most common cause of anemia in pregnancy is
iron deficiency.
Iron therapy is best given orally
76. Take Home Message
The youth need to be educated about diet,
sanitation and personal hygiene
Hookworm infestation should be treated
Pregnant women should be given Iron and
folate supplements
