Rao MPharm Ph D Asst Professor amp HOD Dept of Pharmacy practice Hindu college of pharmacy Gnt AP India Definition Anemia is a hematologic condition in which there is quantitative deficiency of circulating hemoglobin ID: 914388
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Slide1
Anaemias
By
G
Sadasiva
Rao
M.Pharm
., (Ph. D)
Asst.
Professor & HOD
Dept. of Pharmacy practice
Hindu college of pharmacy,
Gnt
, AP, India.
Slide2Definition
Anemia is a hematologic condition in which there is quantitative deficiency of circulating hemoglobin (
Hb
), often accompanied by a reduced number of red blood cells (erythrocytes).
Causes of anemia are blood loss, impaired
erythro
-
poiesis
, and abnormal erythrocyte destruction.
Nutritional deficiencies [iron,
cobalamin
(B
12
),
folate
] are the most common cause of anemia throughout the world.
Erythropoiesis
is a controlled physiologic process. In response to changes in tissue oxygen availability, the kidney regulates production and release of erythropoietin that stimulates the bone marrow to produce and release red blood cells.
Slide3Erythrocytes originate from
pluripotent
stem cells in the bone marrow and undergo multiple steps of differentiation and maturation.
Early stages of red cell production consist of large cells with immature nuclei (
pronormoblasts
and basophilic
normoblasts
).
As cells mature,
Hb
is incorporated, the nucleus is extruded, and cell size decreases.
Various nutrients are needed for normal
erythropoiesis
. Lack of B
12
or
folate
can interfere with cell maturation, resulting in the release of
megaloblasts
(
erythroid
precursors with immature nuclei).
Iron deficiency interferes with
Hb
production and incorporation into the maturing cells, which continue to divide, resulting in the release of smaller cells (
microcytosis
).
Slide4Treatment Goals: Anemias
Identify patients at risk for developing nutritional
anemias
.
Prevent nutritional deficiencies and anemia.
Treat nutritional deficiency and/or anemia by providing the appropriate nutrient.
Document and confirm the deficiency state as the cause of the anemia.
Identify and, when possible, rectify the pathologic state responsible for the deficiency.
Develop therapeutic monitoring plans.
Optimize patient compliance with treatment plan by minimizing treatment side effects, costs, and inconvenience.
Prevent long-term
sequelae
.
Slide5Pathophysiology
Anemia, which has many causes, is not a single disease entity but a sign of disease.
Regardless of the cause, anemia is associated with a reduction in circulating
Hb
because of reduced numbers of erythrocytes or less
Hb
per erythrocyte.
The number of erythrocytes in normal people varies with age, sex, and atmospheric pressure.
People who live at high altitudes have more erythrocytes to compensate for the reduced oxygen in the air.
At sea level, the average man has 5.5 × 10
12
erythrocytes/L (5.5 × 10
6
/mm
3
).
The erythrocytes occupy approximately 47% of the blood and are often referred to as the packed cell volume or
hematocrit
(
Hct
).
Slide6The normal ranges for red blood cell measurements (
Hb
,
Hct
) vary with age and laboratory.
Blood from healthy men contains approximately 9.9
mmol
/L (16 g/
dL
)
Hb
. All these parameters are lower for healthy women.
Values for neonates, which show no sex differences, are higher at birth, but after several weeks they decrease to below those of women. Thereafter the values rise gradually, and at puberty sex differences appear.
The physiologic result of low circulating
Hb
is the reduced capacity for blood to carry oxygen. Consequently, less oxygen is available to tissues, including those of the heart, brain, and muscles, leading to the clinical manifestations of anemia.
Slide7Hemoglobin
Level Chart
Normal
Hemoglobin
Count Ranges Widely Accepted by Physicians
Children
Birth:13.5 to 24.0 g/dl (mean 16.5 g/dl)
<1 mth:10.0 to 20.0 g/dl (mean 13.9 g/dl)
1-2 mths:10.0 to 18.0 g/dl (mean 11.2 g/dl)
2-6 mths:9.5 to 14.0 g/dl (mean 12.6 g/dl)
0.5 to 2 yrs:10.5 to 13.5 g/dl (mean 12.0 g/dl)
2 to 6 yrs:11.5 to 13.5 g/dl (mean 12.5 g/dl)
6-12 yrs:11.5 to 15.5 g/dl (mean 13.5)
Females
Age
12-18 yrs:12.0 to 16.0 g/dl (mean 14.0 g/dl)
Age >18 rs:12.1 to 15.1 g/dl (mean 14.0 g/dl)
Males
12-18 yrs:13.0 to 16.0 g/dl (mean 14.5 g/dl)
>18 yrs:13.6 to 17.7 g/dl (mean 15.5 g/dl)
Slide8Signs and Symptoms
Cardiomegaly
and high-output heart failure also are possible in severe cases.
Although the symptoms of anemia are distinctive, they can also be manifestations of other disorders, such as cancer or an inflammatory process.
A comprehensive history and physical examination are important in the assessment of the anemic patient.
More specifically, dietary habits, drug histories, surgical procedures, and occupation should be documented.
Careful questioning about blood loss, menses, gastrointestinal symptoms, and history of pregnancy may provide useful information.
In addition, vitamin deficiencies may cause other symptoms before overt anemia develops. Neurologic or oral changes may occur with B
12
deficiency and may precede anemia.
Slide9Signs and Symptoms of Anemia and Vitamin Deficiency
Anemia in General
Iron Deficiency
Vitamin B
12
Deficiency
Fatigue
Pallor
Dyspnea
Light-headedness
Dizziness
Palpitations
Increased heart rate
Chest pain
Loss of concentration
Development delays,
Behavioral disturbances,
Altered central nervous system development,
Impaired work capacity,
Preterm delivery,
Delivery of low-
birthweight
baby.
Peripheral neuropathy,
“Strange” feeling in extremities,
Loss of hand coordination,
Deterioration in hand-writing,
Tingling of extremities,
Loss of
proprioception
,
Depression,
Psychosis,
Spinal cord degeneration,
Sore tongue or mouth.
Slide10Diagnosis
A detailed medical and medication history along with hematologic and biochemical tests, including a full blood screen, are essential for identifying the type of anemia and in many cases directing the treatment.
As the nutritional
anemias
progress in stages (normal, negative nutrient balance, nutrient depletion, nutrient deficiency, anemia), monitoring early indicators of depletion may prevent the progression to overt anemia
Slide11High-Risk Populations for Development of Nutritional
Anemias
Population
Predisposing Factors
Type of Anemia
Children
Growth, poor diet
Iron deficiency
Teenagers
Growth, diet, men-struation
Iron deficiency
Women
Menstruation, diet
Iron deficiency
Pregnant
women
Fetal needs, diet
Iron, folate deficiency
Older adults
Achlorhydria
Iron, B
12
deficiency
Diet
Iron, B
12
, folate deficiency
Underlying disease
Iron, B
12
,
folate
deficiency
Organ function
Iron, B
12
,
folate
deficiency
Drug-induced
Iron, B
12
,
folate
defiency
Slide12Alcoholics
Diet
Iron, folate deficiency
Liver or gastroin-testinal disease
Iron, B
12
, folate deficiency
Patients with human
immu-nodeficiency
virus
Achlorhydria
Iron, B
12
deficiency
Diet
Iron, B
12
, folate deficiency
Drug-induced
B
12
,
folate
deficiency
Slide13Hematologic Tests
Hematologic tests are less expensive and more available than biochemical tests and provide information on the characteristics of the red blood cells.
A full blood screen provides information on
Hb
and
Hct
levels as well as cell size and color.
Many aspects of the cellular elements of blood can be quantified by automated blood analyzers, including blood
Hb
concentration, cell counts, and the mean corpuscular volume (MCV).
From these primary measurements, the
Hct
, mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC) are calculated automatically.
Slide14MCV, MCH, and MCHC are collectively known as the erythrocyte indices.
The MCV correlates with cell size (smaller cells take up less volume) and is particularly valuable in differentiating
microcytic
anemias
, which have a reduced MCV (<80
fL
), from
macrocytic
anemias
, which have a greater than normal MCV (>100
fL
).
However, the MCV may appear normal in mixed
anemias
, where the
microcytic
cells of iron deficiency are counterbalanced by the
macrocytic
cells of B
12
or
folate
deficiency
Slide15The MCH and MCHC provide information on cell color [lower
Hb
, less color (
hypochromia
)].
Hypochromic
anemias
, such as iron deficiency anemia, have a low MCHC indicating lower-than-normal
Hb
concentrations.
Another parameter, the red blood cell distribution width (RDW), is an index of the variation in cell volume of the erythrocyte population. With iron deficiency anemia, there is an increased RDW, reflecting the
anisocytosis
(cells of unequal size) seen in blood smears.
Slide16Other hematologic investigations include
reticulocyte
counts, differential white cell count, platelet count, and microscopic examination of peripheral blood smears and bone marrow aspirates.
The normal life span of an erythrocyte is 120 days. As old erythrocytes are removed from the circulation by the
reticuloendothelial
system, they are replaced by young erythrocytes from the bone marrow.
These immature cells, called
reticulocytes
, make up 1% to 1.5% of the total erythrocyte population in a normal person.
Because
reticulocytes
are a young population of red blood cells, they are an important marker of bone marrow activity.
Reticulocytosis
, an increase in
reticulocyte
numbers, indicates increased bone marrow activity.
Transient
reticulocytosis
often occurs in response to iron, B
12
, or folic acid therapy for the respective deficiency states.
Slide17Biochemical Tests
Biochemical tests for assessing
anemias
include measurement of serum iron, vitamin concentrations (B
12
,
folate
),
transport proteins (
transferrin
,
transcobalamin
II [TCII]),
saturation of protein- binding sites (
transferrin
saturation), and
storage amounts (
ferritin
).
More specific tests also can be used:
serum
transferrin
receptors (
TfR
),
erythrocyte zinc
protoporphyrin
(ZPP) concentration (iron deficiency),
homocysteine
(
Hcy
) and
methylmalonic
acid (MMA) serum concentrations (B
12
and
folate
deficiencies), and antibodies to intrinsic factor (IF) or parietal cells (B
12
).
Slide18Component
Specimen
Conventional
Hematocrit
B
M
45%–52%
F
37%–48%
Hemoglobin
B
M
13%–18% g/dL
F
12%–16% g/dL
Erythrocyte count
B
4.2%–5.9% × 10
6
/mm
Reticulocyte
count
B
0.5%–1.5% erythrocytes
Mean corpuscular volume
Ery
80–94
f mol
Mean corpuscular hemoglobin
Ery
27–32 pg
Mean corpuscular hemoglobin concentration
Ery
32–36 g/
dL
Slide19Red cell distribution width
Ery
11.5%–14.5%
Iron
S
M
80–200 µg/dL
F
60–190 µg/dL
Transferrin
S
170–370 mg/dL
Total iron-binding capacity
S
250–410
g/
mL
Transferrin
saturation
S
20%–55%
Transferrin receptors
S
2.8–8.5 mg/L
Ferritin
S
M>F
1.5–30 µg/dL
Zinc protoporphyrin
<70 µg/
dL
red cell
Slide20Folate (as pteroglutamic acid)
Normal
S
2–10
ng
/
mL
Borderline
S
1–1.9
ng
/
mL
Ery
150–800
ng
/
mL
Vitamin B
12
S
200–1,000 pg/
mL
Methylmalonic acid (mean ± 3 SD)
S
53–376 nmol/L
Homocysteine (mean ± 3 SD)
S
4.1–21.3 µmol/L
Holo-transcobalamin II
P
Mean for control group + SD
B, whole blood; M, male; F, female,
Ery
, erythrocyte; S,
serum.
Slide21Treatment
Treating nutritional anemia involves identifying and correcting the cause if possible, replenishing deficient nutrients, and alleviating symptoms.
This may involve restoring missing nutrients, restoring blood volume by transfusions, or treating the cause by medical or surgical methods.
Inadequate dietary intake of nutrients often is a cause of nutritional deficiencies that may lead to anemia.
Dietary counseling and follow-up may be sufficient for some patients, but many need supplementation.
Careful assessment of the patient's drug history may help identify possible
pharmacotherapeutic
agents that affect nutrient status or red blood cells directly.
Some deficiencies may necessitate long-term or lifelong therapy, and patients must be counseled and monitored appropriately.
Slide22Iron Deficiency Anemia
Slide23Iron deficiency occurs when the body's iron stores are insufficient for the normal formation of
Hb
, iron-containing enzymes, and other functional iron compounds such as
myoglobin
and those of the
cytochrome
system.
Iron deficiency can be classified according to its severity : normal stores; negative iron balance; iron store depletion (low serum
ferritin
); decreased serum iron [low serum iron, increased total iron-binding capacity (TIBC)]; and anemia (reduced
Hb
with
microcytic
,
hypochromic
erythrocytes).
Slide24Erythrocytes of patients with mild, early-stage iron deficiency often appear to be normal in color and size (i.e.,
normochromic
,
normocytic
).
Other conditions with low MCV and MCHC, such as
thalassemia
and anemia of chronic disease, generally can be differentiated from iron deficiency anemia by assessment of various laboratory values
Slide25Stage
Serum
Ferritin
(µg/L)
Serum Iron
Total Iron-binding Capacity
Zinc
Protoporphyrin
Trans
ferrin
Saturation (%)
Trans
ferrin
Receptors
Hemo
globin
Normal
>15
nl
nl
nl
>16
nl
nl
Negative balance
>15
nl
nl
nl
>16
nl
nl
Iron store depletion
<15
nl
nl
nl
>16
nl
nl
Iron
deficiency
<15
↓
nl
↑
<16
↑
nl
Iron deficiency anemia
<15
↓
↑
↑
<16
↑
↓
Anemia of chronic desease
↓, ↑, or nl
nl
nl
or ↓
↑
nl
or ↓
nl
↓
Thalassemia
nl
or ↑
nl
nl
nl
nl
nl
↓
Slide26Physiologic Importance of Iron
Iron is an essential element for many physiologic processes, including
erythropoiesis
, tissue respiration, and several enzyme-catalyzed reactions.
The average adult body contains 3 to 5 g elemental iron, distributed into two major components: functional iron and storage.
Functional iron exists predominantly as
Hb
(1.5–3 g) in circulating erythrocytes, with lesser amounts in iron containing proteins such as
myoglobin
and
cytochromes
(0.4 g), 3 to 7 mg bound to
transferrin
in plasma, and the remainder in storage iron in the form of
ferritin
or
hemosiderin
.
Slide27Slide28Hb
is the oxygen-binding protein in erythrocytes that transports oxygen absorbed from the lungs to the tissues. Each
Hb
molecule consists of a
globin
surrounded by four
heme
groups that contain all the iron.
Globin
consists of linked pairs of polypeptide chains. Fetal
Hb
has two α- and two γ-
globin
chains. In normal erythrocyte development, the γ-chains are replaced by β-chains, and a normal human adult has two α- and two β-chains.
The composition of these chains differs in patients with genetically determined disorders such as
thalassemia
and sickle cell anemia
Slide29Hb
forms an unstable, reversible bond with oxygen, allowing oxygen release at a lower oxygen tension that is encountered in the tissues.
In iron deficiency anemia and other chronic
anemias
,
Hb
has a reduced affinity for oxygen.
This allows oxygen to transfer more readily from the erythrocytes to the tissues.
Myoglobin
, a
hemoprotein
in muscle, accepts oxygen from
Hb
and acts as an oxygen store in muscle.
If oxygen supply is limited,
myoglobin
releases its oxygen to
cytochrome
oxidase
, the terminal enzyme in the mitochondrial respiratory chain, which has a higher affinity for oxygen than
myoglobin
, allowing oxidative
phosphorylation
to occur.
Slide30Transferrin
, a β-globulin synthesized by the liver, is a specific iron-binding protein in blood that transports iron through the plasma and
extravascular
space.
Each molecule of
transferrin
can bind two molecules of iron in the ferric state (Fe
3+
).
In normal circumstances, it is only about 30% to 50% saturated. The ability of
transferrin
to bind iron is called the iron-binding capacity.
The total iron binding capacity (TIBC), which reflects serum
transferrin
concentrations, is a well-recognized value in the investigation of
anemias
.
It represents the amount of iron that can bind to
transferrin
to give 100% saturation of the binding sites.
The TIBC is high in iron deficiency and low in iron overload. Most cells obtain their iron from
transferrin
.
In the case of
reticulocytes
and developing erythrocytes in the bone marrow, most of the iron taken up is used for
Hb
synthesis.
Slide31Storage iron
(0.3–1.5 g), in the form of
ferritin
and
hemosiderin
, is located mainly in the
parenchymal
cells of the liver, the
reticuloendothelial
cells of the spleen, and bone marrow, and it replenishes functional iron.
Iron stores account for one third of body iron in healthy men.
Iron stores are more variable and are generally lower in children and women of childbearing potential.
Low iron stores are an early sign of iron deficiency and may help differentiate between iron deficiency anemia and other causes of anemia
Slide32Iron Needs
Body iron usually is kept constant by a delicate balance between the amount lost and absorbed.
There is no physiologic mechanism for excreting iron in humans.
Iron balance is a conservative system, and in the normal adult, even if iron intake is negligible, it takes at least 2 to 3 years to develop iron deficiency
Slide33Iron needs are determined by total losses from the body.
Daily iron needs vary according to age and sex.
Total daily iron loss amounts to 1 mg daily in men.
Iron losses in women of childbearing potential are higher than those in men because of menstruation and pregnancy.
Iron is lost from the gastrointestinal tract by sloughing of iron-containing mucosal cells and
extravasation
of erythrocytes, by skin exfoliation, and by shedding of urinary tract epithelial cells.
Iron loss through sweat is minimal
Slide34Blood loss in menstruating women varies, but if it exceeds 80
mL
, it can lead to iron deficiency.
Average iron losses through menstruation are about 0.3 to 0.5 mg daily.
Menstrual iron losses are lower in women taking oral contraceptives and higher in those using an intrauterine device.
Slide35Iron needs increase to 3 to 4 mg daily during pregnancy to account for obligatory losses, the expanded maternal erythrocyte mass that occurs in pregnancy and in the placenta and fetus.
Iron needs are greatest in the second and third trimester when the highest fetal erythrocyte needs occur.
Some of the iron incorporated in the expanded maternal erythrocyte mass returns to the iron pool after pregnancy, but
peripartum
blood loss partly nullifies this contribution.
Because menstruation does not start until several weeks after delivery, iron losses are reduced. However, breast-feeding offsets some of the gain.
Slide36The need for iron is high in the first year of life and throughout childhood because of rapid growth and
erythropoiesis
during this period.
Normal full-term infants need to absorb a minimum of 0.3 mg of iron daily in the first year of life.
Premature infants can need up to 1 mg daily. Children's iron needs increase with age
Slide37Recommended Daily Allowances for Iron, Folic Acid, and Vitamin B
12
Age
Iron (mg/day)
Folic Acid (µg/day)
Vitamin B
12
(µg/day)
Infants
0–6 months
0.27
65
0.4
7–12 months
11
80
0.5
Children
1–3 years
7
150
0.9
4–8 years
10
200
1.2
Males
9–13 years
8
300
1.8
14–18 years
11
400
2.4
≥19
years
8
400
2.4
Slide38Females
9–13 years
8
300
1.8
14–18 years
15
400
2.4
19–30 years
18
400
2.4
31–50 years
18
400
2.4
50–70 years
8
400
2.4
>70 years
8
400
2.4
Slide39Pregnancy
≤18 years
27
600
2.6
19–30 years
27
600
2.6
31–50 years
27
600
2.6
Lactation
≤18 years
10
500
2.8
19–30 years
9
500
2.8
31–50 years
9
500
2.8
Slide40Iron Absorption
Iron absorption is regulated by iron needs and body stores.
When iron stores are low or depleted, a higher proportion of available iron is absorbed. Absorption decreases when the stores are replete.
The serum
ferritin
concentration, which reflects body iron stores, is inversely related to iron absorption.
In some clinical states, such as primary
hemochromatosis
,
thalassemia
, and
sideroblastic
anemia, iron absorption remains normal and even elevated despite increased iron stores.
Slide41The iron content of food and its bioavailability determine if the diet can meet physiologic needs.
Dietary iron is present as two major pools:
heme
iron and
nonheme
iron.
Heme
iron, found only in meats, is two to three times more absorbable than
nonheme
iron, found in plant-based and iron- fortified foods.
Ingested
heme
compounds and organic
nonheme
iron complexes are broken down in the acid environment of the stomach to ferric ions (Fe
3+
) and
heme
molecules, respectively.
The stomach's acidity promotes reduction of iron from the ferric state to the ferrous state (Fe
2+
), which is better absorbed.
Patients with
achlorhydria
secondary to age or
gastrectomy
tend to absorb
nonheme
iron poorly.
Slide42Iron is absorbed primarily in the upper duodenum. The iron-absorptive capacity is limited by the rate at which iron is transferred from the intestinal lumen to the plasma.
The reduced (ferrous) iron binds to specific sites on the lumen and is actively carried across the intestinal membrane.
Iron absorbed by these cells is incorporated into an iron carrier pool, most of which is deposited as
ferritin
or used by the mitochondria for enzyme synthesis.
A small amount of iron is lost through the normal sloughing of the mucosal cells in the gastrointestinal tract.
A smaller proportion of the iron from the carrier pool is transferred to the plasma, where the ferric form binds tightly to
transferrin
.
Slide43Slide44A number of factors can inhibit or promote iron absorption. Foods that can reduce iron absorption by forming less soluble complexes include coffee, tea, milk and milk products, eggs, whole grain breads and cereals, and any food containing bicarbonates, carbonates, oxalates, or phosphates.
Commercial processing or enhancers can improve absorption from food in some cases. Enhancers of
nonheme
iron absorption are food acids such as citric, lactic, or ascorbic acids, and meats.
Slide45Ascorbic acid, the most powerful promoter, has a dose-related effect on
nonheme
iron absorption.
In its presence, ferric iron is converted to the ferrous state, maintaining iron solubility in the alkaline environment of the duodenum and upper jejunum.
Ascorbic acid also forms an alkaline-stable
chelate
with ferric chloride in the stomach.
Meat, itself a rich source of iron, also promotes absorption of
nonheme
iron. Approximately 1 g of meat enhances
nonheme
iron absorption to about the same extent as 1 mg of ascorbic acid.
Citric acid, a common food additive and a less powerful promoter of iron absorption, has an additive effect to ascorbic acid.
Slide46Factor
Associations
Promoting absorption
Inorganic iron
Ionic iron, particularly in the ferrous form, is better absorbed than ferric iron and organically bound iron.
Ascorbic acid
Ascorbic acid helps to convert ferric iron to ferrous iron.
Acid
Gastric hydrochloric acid promotes the release and conversion of dietary iron to the ferrous form.
Chelates
Iron chelated to low-molecular-weight substances such as sugars (fructose and sucrose), amino acids, and succinate facilitates iron binding to the intestinal mucosa.
Clinical states
Iron deficiency, increased
erythropoiesis
, pregnancy, anoxia, and pyridoxine deficiency promote absorption.
Slide47Factor
Associations
Reducing absorption
Alkaline
Alkaline pancreatic secretions containing phosphate probably convert iron to insoluble ferric hydroxide; antacids.
Dietary
Dietary phosphates and phytates in cereals and tannins in tea probably complex iron.
Clinical states
Chronic diarrhea,
steatorrhea
, adequate iron stores, decreased
erythropoiesis
, and acute or chronic inflammation reduce absorption.
Medications
Anatacids
, tetracycline
Slide48Epidemiology
Iron deficiency, estimated to occur in more than 2.5 billion people throughout the world, is the most common cause of nutritional anemia.
Data from the third Nutritional Health and Nutrition Examination Survey (NHANES III) in the United States indicated that the incidence of iron deficiency was highest for toddlers aged 1 to 2 years, adolescent girls, and women of childbearing potential, with iron deficiency anemia occurring in 3%, 2%, and 5%, respectively.
For women of childbearing potential, iron deficiency was more common in minorities, people with lower incomes, and
multiparous
women.
Iron deficiency occurred in less than 1% of men and adolescent boys between 12 and 50 years of age and in 4% of men 70 years and older.
Slide49Etiology
Factor
Association
Dietary
Starvation, poverty, vegetarianism, religious practice, food fads
Blood loss
Women and girls
Menstruation, postmenopausal bleeding, pregnancy
General
Esophageal
varices
, peptic ulcer, drug-induced gastritis, carcinomas of stomach and colon, ulcerative colitis, hemorrhoids, renal or bladder lesions (
hematuria
), hookworm infestation, other organ bleeding (
hemoptysis
), frequent blood donation, athletic training, widespread bleeding disorders
Malabsorption
Celiac disease (gluten-induced enteropathy), partial and total gastrectomy, chronic inflammation
Increased requirements
Rapid growth (as in childhood and adolescence), pregnancy;
erythropoiesis
Slide50Signs and Symptoms
The usual signs and symptoms of iron deficiency anemia are often present .
Other problems caused by the gross epithelial changes associated with chronic iron deficiency include brittle or spoon-shaped nails, angular
stomatitis
, atrophic tongue, pharyngeal and esophageal webs causing
dysphagia
, and atrophic gastric mucosa.
Iron deficiency, in addition to its hematologic effects, may also be associated with diverse problems such as impaired work performance; low
birthweight
, prematurity, and increased
perinatal
mortality and impaired psychomotor behavior, cognitive function, and central nervous system development in infants and young children.
Slide51A common symptom of iron deficiency anemia is pica, a condition in which the person craves unusual substances that generally have no nutritional value, such as clay (
geophagia
), paper products, or starch (
amylophagia
).
Pagophagia
(pica for ice), or habitual ice eating, is a common form of pica in some communities.
Other people consume earth and particles of clay cooking pots. Such ingestions have led to metabolic problems, including heavy metal poisoning.
Slide52Diagnosis
Most cases of iron deficiency anemia are identified on the basis of a medical history, complete blood count, and peripheral smears.
In iron deficiency anemia, hematologic changes are evident only after all body iron stores have been depleted and there is insufficient iron to maintain normal erythrocyte morphology and mass .
Blood
Hb
concentrations and erythrocyte numbers are normal in mild cases. Serum
ferritin
is the first parameter to change with iron deficiency.
As the deficiency worsens, the MCV and erythrocyte count decrease markedly, the RDW increases, and eventually, the
Hb
decreases.
When
Hb
concentrations are 4.4
mmol
per liter (7 g/
dL
) or less for women or 5.6
mmol
per liter (9 g/
dL
) or less for men, microscopic examination of peripheral blood smears shows
hypochromia
and
poikilocytosis
.
Slide53To diagnose iron deficiency
anemia
, your doctor may run tests to look for:
Red blood cell size and
color
.
With iron deficiency
anemia
, red blood cells are smaller and paler in
color
than normal.
Hematocrit
.
This is the percentage of your blood volume made up by red blood cells. Normal levels are generally between 34.9 and 44.5 percent for adult women and 38.8 to 50 percent for adult men. These values may change depending on your age.
Hemoglobin
.
Lower than normal
hemoglobin
levels indicate
anemia
. The normal
hemoglobin
range is generally defined as 13.5 to 17.5 grams (g) of
hemoglobin
per
deciliter
(
dL
) of blood for men and 12.0 to 15.5 g/
dL
for women. The normal ranges for children vary depending on the child's age and sex.
Ferritin
.
This protein helps store iron in your body, and a low level of
ferritin
usually indicates a low level of stored iron.
Slide54Prevention
You can reduce your risk of iron deficiency
anemia
by choosing iron-rich foods.
Choose iron-rich foods
Foods rich in iron include:
Red meat, pork and poultry
Seafood
Beans
Dark green leafy vegetables, such as spinach
Dried fruit, such as raisins and apricots
Iron-fortified cereals, breads and pastas
Peas
Slide55Your body absorbs more iron from meat than it does from other sources.
If you choose to not eat meat, you may need to increase your intake of iron-rich, plant-based foods to absorb the same amount of iron as does someone who eats meat.
Slide56Choose foods containing vitamin C to enhance iron absorption
You can enhance your body's absorption of iron by drinking citrus juice or eating other foods rich in vitamin C at the same time that you eat high-iron foods. Vitamin C in citrus juices, like orange juice, helps your body to better absorb dietary iron.
Vitamin C is also found in:
Broccoli
Grapefruit
Kiwi
Leafy greens
Melons
Oranges
Peppers
Strawberries
Tangerines
Tomatoes
Slide57Preventing iron deficiency
anemia
in infants
To prevent iron deficiency
anemia
in infants, feed your baby breast milk or iron-fortified formula for the first year.
Cow's milk isn't a good source of iron for babies and isn't recommended for infants under 1 year.
After age 6 months, start feeding your baby iron-fortified cereals or pureed meats at least twice a day to boost iron intake.
After one year, be sure children don't drink more than 20 ounces (591
milliliters
) of milk a day. Too much milk often takes the place of other foods, including those that are rich in iron.
Slide58Treatment
Although dietary improvements may reduce the risk of iron deficiency, the poor absorption of iron from foods limits the usefulness of dietary therapy in correcting an existing deficiency.
Therefore, iron deficiency generally is corrected with oral or
parenteral
iron.
Most iron therapy is given by the oral route, with few situations justifying the use of
parenteral
iron.
With appropriate therapy, the
Hb
levels improve within a few weeks, and the patient feels better.
Adequate iron must be supplied in the early stages of treatment to optimize the response.
Slide59Pharmacotherapy
Oral Iron Therapy
Oral iron supplementation is safer, more convenient, and less expensive than
parenteral
therapy.
Oral iron preparations are salt forms, which vary in elemental iron content, cost, and effectiveness.
Iron absorption from ferrous salts is considered better than that from ferric salts.
The dosage of the iron product is based on the elemental iron content.
In general, 30 to 40 mg daily elemental iron is used to treat iron deficiency states.
These numbers are derived from calculating the maximum rate of
Hb
regeneration
Slide60Since only 10% to 20% of iron is absorbed, 200 to 400 mg of iron would result in absorption of approximately 40 mg elemental iron.
Ferrous sulfate tablets contain 20% elemental iron (60 mg iron per 300-mg tablet).
The standard dosing of ferrous sulfate is 300 mg three times a day, which provides 180 mg of elemental iron per day.
Assuming 20% absorption, only about 60mg of elemental iron will be absorbed.
Maximum absorption occurs if iron is taken before or between meals.
Slide61The most common side effects of oral iron therapy are
epigastric
distress, abdominal cramping, nausea, diarrhea, and constipation caused by gastric irritation.
The reported incidence of these side effects ranges from 15% to 46% with daily dosing.
These side effects appear to be dose related. Options for minimizing these side effects include reducing the daily dose, taking the iron with food, or changing to once-a-week dosing.
Use of enteric-coated products to minimize gastrointestinal effects is not recommended because the coating prevents dissolution in the stomach, thus minimizing iron absorption.
Iron therapy can cause the stools to appear black. Patients should be educated about differences between stool changes from iron and those associated with gastrointestinal bleeding.
Slide62Iron absorption may be reduced in patients with reduced gastric acid production or prior gastrointestinal surgeries.
Antacids, histamine-2 blockers, and proton pump inhibitors may also decrease iron absorption .
A careful medication history should be obtained to check for potential drug interactions before an absorption test or
parenteral
therapy is initiated.
Slide63Parenteral Iron Therapy
Oral iron replacement therapy is usually sufficient for most patients.
Oral iron may be inadequate in patients who are intolerant to oral iron, noncompliant, have abnormal absorption due to surgery or gastrointestinal conditions, or significant blood loss.
Parenteral
iron may be necessary in these patients.
Iron deficiency anemia in patients with chronic kidney disease and
hemodialysis
patients receiving erythropoietin or
darbepoetin
Slide64The amount of
parenteral
iron needed to replenish iron stores and restore
Hb
levels in patients with iron de-
ficiency
anemia can be approximated using the following formula:
dose = 0.3 X body
wight
(lbs) X [100 –
Hb
(
gms
/dl) X 100/14.8]
The formula can be modified to use kilograms instead of pounds:
dose = 0.66 X body
wight
(
kgs
) X [100 –
Hb
(
gms
/dl) X 100/14.8]
For children weighing less than 15 kg, the normal mean
Hb
of 12 g/
dL
is used in place of 14.8 g/
dL
in the equation.
Slide65Iron Dextran
Iron
dextran
is a complex of ferric hydroxide and
dextran
. Following administration, the iron
dextran
complex is separated by the
reticuloendothelial
system.
The iron that is released then binds to
transferrin
for transport to the liver, spleen, and bone marrow.
Iron
dextran
can be given as an intravenous infusion, slow intravenous injection, or by intramuscular injection.
Regardless of the route, a test dose of 0.5
mL
(25 mg) should be given before therapy is initiated.
The test dose should be given by the same route as the intended therapy. Patients should be observed for at least 1 hour for any reactions.
Slide66Most adverse reactions occur during or shortly after the test dose and range from mild transient reactions to life-threatening anaphylactic reactions.
Mild reactions are generally transient and include
dyspnea
, headache, nausea, vomiting, flushing, itching,
urticaria
, fever, hives, and chest, abdominal, or back pain.
Anaphylactic reactions are characterized sudden onset of respiratory difficulty or cardiovascular collapse.
Emergency medications such as epinephrine,
diphenhydramine
, and corticosteroids to treat the anaphylactic reaction should be readily available.
Slide67Iron Sucrose
Iron sucrose is a complex of ferric hydroxide and sucrose. Like iron
dextran
, iron sucrose is dissociated into iron and sucrose in the
reticuloendothelial
system.
Iron sucrose (
Venofer
) was approved by the FDA in November of 2000 for treatment of iron deficiency anemia in
nondialysis
and dialysis-dependent chronic kidney disease patients receiving erythropoietin.
The recommended dose of iron sucrose in
hemodialysis
-dependent patients is 100 mg (5
mL
) undiluted as a slow intravenous injection over 2 to 5 minutes or diluted in 100
mL
of 0.9% normal saline given as an intravenous infusion over 15 minutes on consecutive dialysis sessions to a cumulative dose of 1,000 mg.
Slide68In
nondi
-
alysis
patients with chronic kidney disease, the recommended dose is 200 mg, given as a slow intravenous injection over 2 to 5 minutes on five different occasions in a 14-day period to a cumulative dose of 1,000 mg.
Doses of 500 mg diluted in 250
mL
of 0.9% normal saline given over 3.5 to 4 hours on days 1 and 14 have been administered.
For peritoneal dialysis patients, a cumulative dose of 1,000 mg is given in three divided doses within a 28-day period, with two infusions of 300 mg each given over 1.5 hours 14 days apart followed by one 400-mg infusion over 2.5 hours 14 days later.
Iron sucrose is more readily available for
erythropoiesis
than iron
dextran
, with increases in hemoglobin noted after 1 week of
administration.Iron
sucrose has been used in patients with documented iron
dextran
sensitivity
Slide69Ferric Gluconate
Sodium ferric
gluconate
complex in sucrose was approved by the FDA in February 1999 for the treatment of patients with iron deficiency anemia undergoing chronic
hemodialysis
who are receiving erythropoietin therapy.
The recommended dose is 125 mg (10
mL
) diluted in 100
mL
of 0.9% normal saline given as an intravenous infusion over 1 hour.
It can also be given undiluted as a slow intravenous injection (not to exceed 12.5 mg/min).
Most patients will require a cumulative dose of 1,000 mg given over eight sequential dialysis sessions to achieve the desired hemoglobin or
hematocrit
response.
Doses exceeding 125 mg and/or infusion rates exceeding the recommended rate have been associated with a higher incidence of adverse reactions.
Ferric
gluconate
has been safely administered to iron
dextran
-sensitive patients
Slide70Parenteral Iron Toxicities
Adverse reactions to iron
dextran
, iron sucrose, and ferric
gluconate
have been reported in 50%, 36%, and 35% of patients, respectively.
The most common adverse events include hypotension, hypertension, nausea, vomiting, diarrhea, abdominal pain,
bradycardia
, chest pain, headache, fever,
pruritus
, malaise,
arthralgias
,
myalgias
, back pain, and allergic reactions
Slide71Contraindications to Iron Therapy
Iron preparations should not be used in conditions, such as
hemochromatosis
and
hemosiderosis
, that already signify iron overload.
In
thalassemia
and anemic conditions with chronic inflammatory disease, such as rheumatoid arthritis, iron is contraindicated because these conditions have normal to high iron stores because of impaired use of iron.
Care must be exercised in giving iron to alcoholic patients because of elevated iron stores.
Patients with alcoholic liver disease, such as cirrhosis, generally do not suffer from
hemochromatosis
, but those with marked increases in iron deposition and body stores may have genetically determined
hemochromatosis
Slide72Iron Toxicity
Iron toxicity can be acute, such as in overdose and accidental poisoning, or chronic, as in overload that occurs in
hemochromatosis
,
hemosiderosis
, and
thalassemia
.
A person with iron overload usually has more than 4 g body iron. Iron, which is ordinarily stored in
reticuloendothelial
cells, is deposited as
ferritin
and
hemosiderin
into
hepatocytes
of the liver and eventually other tissues and organs.
Hemochromatosis
is associated with severe iron overload, and may lead to liver and heart failure
Slide73Vitamin B12 Deficiency
Anemia
Slide74Megaloblastic Anemias
Megaloblastic
anemia is a subclass of the
macrocytic
anemias
.
Megaloblastic
anemia is characterized by a lowered blood
Hb
mass because of reduced
erythropoiesis
secondary to defective DNA synthesis in the developing
erythroid
cells of the bone marrow.
Nonmegaloblastic
macrocytic
anemias
(those not resulting from disorders of DNA synthesis) are caused primarily by alcoholism, liver disease, and hypothyroidism.
Deficiencies of vitamin B
12
or
folate
are the major causes of
megaloblastic
anemia, followed by drug-induced interference, direct or indirect, with DNA synthesis or nutritional status.
Slide75Reduced availability or absence of one-carbon-unit coenzymes, such as
methylcobalamin
(active B
12
) or
formyltetrahydrofolic
acid (active folic acid), results in impaired DNA synthesis in developing
erythroid
cells.
These cells do not divide normally, and fewer large but well-
hemoglobinated
cells (
megaloblasts
) form in the bone marrow.
The resulting
megaloblasts
are characterized by an abnormal nucleus because of greater
cytoplasmic
(rather than nuclear) maturity.
Cells released into the circulation are larger than normal (
macrocytic
) and are generally
normochromic
.
Morphologic changes observed in the peripheral smear include macro-
ovalocyte
erythrocytes and
multilobed
neutrophilic
granulocytes.
These erythrocytes have a reduced life span.
Slide76In addition to the
erythroid
changes, similar effects on other
hemopoietic
cell lines in the bone marrow can lead to
leukopenia
, thrombocytopenia, or
pancytopenia
.
Other rapidly dividing tissue can also be affected, particularly the mucosal epithelium of the gastrointestinal tract.
Slide77Vitamin B12 Deficiency Anemia
Having vitamin B12 deficiency means that your body does not have enough of this vitamin.
You need B12 to make red blood cells , which carry oxygen through your body.
Not having enough B12 can lead to
anemia
, which means your body does not have enough red blood cells to do the job.
This can make you feel weak and tired. Vitamin B12 deficiency can cause damage to your nerves and can affect memory and thinking.
Slide78Physiologic Importance of Vitamin B12
Vitamin B
12
, also known as
cobalamin
(
Cbl
), occurs in synthetic and biologically active forms.
It is a cobalt-containing vitamin that cannot be synthesized by mammalian tissue.
Therefore, it must be obtained via dietary intake or supplementation.
Some bacterial synthesis of B
12
occurs in the large bowel and the
cecum
, but there is no absorption at these sites.
Slide79B
12
is an essential cofactor for three known enzymatic reactions:
conversion of
methylmalonyl
-Co A to
succinyl
-Co A, a critical step in propionate metabolism;
methylation
of
Hcy
to
methionine
by
methionine
synthetase
; and
interconversion
of
leucine
and β-
leucine
by
leucine
2,3-aminomutase.
B
12
deficiency inhibits the activity of these enzymes, resulting in increases in metabolites such as MMA and
Hcy
.
Some speculate that excess of 2-MMA (part of the conversion of
methylmalonyl
-Co A to
succinyl
-Co A) may be associated with the neurologic symptoms of B
12
deficiency
Slide80Vitamin B12 Needs
The daily requirement for humans is 0.4 to 2.4 µg, and higher in pregnant and lactating mothers.
The average diet in the United States supplies 5 to 15 µg/day, but there is a wide variation.
Some diets, such as vegan, macrobiotic, or weight-reduction diets that drastically restrict food selection, may not meet the minimum daily needs.
The total body stores amount to 2 to 5 mg, mainly in the liver.
Thus, B
12
deficiency takes years to develop.
Slide81Vitamin B12 Absorption and Metabolism
Slide82What causes vitamin B12 deficiency anemia?
Most people get more than enough B12 from eating meat, eggs, milk, and cheese. Normally, the vitamin is absorbed by your digestive system-your stomach and intestines.
Vitamin B12 deficiency
anemia
usually happens when the digestive system is not able to absorb the vitamin. This can happen if:
You have pernicious
anemia
. In this
anemia
, your body destroys the cells in your stomach that help you absorb vitamin B12.
You have had surgery to remove part of the stomach or the last part of your small intestine, called the ileum . This includes some types of surgery used to help very overweight people lose weight.
You have problems with the way your body digests food, such as
sprue
(also called celiac disease),
Crohn's
disease, bacteria growth in the small intestine, or a parasite.
Slide83This
anemia
can also happen if you don't eat enough foods with B12, but this is rare.
People who eat a vegan diet and older adults who don't eat a variety of foods may need to take a daily vitamin pill to get enough B12.
Other causes include drinking alcohol and taking some prescription and
nonprescription
medicines
Slide84What is the recommended daily amount of vitamin B12?
The amount of vitamin B12 you need depends on your age.
Daily recommended B12:
Age (years)
Daily amount of B12 (micrograms)
1-3
0.9 mcg
4-8
1.2 mcg
9-13
1.8 mcg
14 and older
2.4 mcg
Pregnant
women
2.6 mcg
Breast
-feeding women
2.8 mcg
Slide85What foods contain B12?
Vitamin B12 is found in foods from animals, such as meat, seafood, milk products, poultry, and eggs.
It is not in foods from plants unless it has been added to the food (fortified). Some foods, like cereals, are fortified with vitamin B12.
Supplements containing only B12, or B12 along with other B vitamins and/or
folate
, are readily available.
Also, B12 is usually in multivitamins. Check the label to find out how much B12 is in a supplement.
Slide86Estimates of B12 in certain foods
Food
Serving size
B12 amount (microgram)
Beef
liver
3 ounces
71 mcg
Clams
3 ounces
84 mcg
Cereal fortified with 100% daily value for B12
1 serving
6 mcg
Rainbow trout
3 ounces
3 mcg
Nonfat plain yogurt
8 ounces
1 mcg
Large egg
1 egg
½ mcg
Chicken
breast
½ breast
½ mcg
Slide87What are the symptoms?
If your vitamin B12 deficiency is mild, you may not have symptoms or you may not notice them. Some people may think they are just the result of growing older. As the
anemia
gets worse, you may:
Feel weak, tired, and lightheaded.
Have pale skin.
Have a sore, red tongue or bleeding gums.
Feel sick to your stomach and lose weight.
Have
diarrhea
or constipation.
If the level of vitamin B12 stays low for a long time, it can damage your nerve cells. If this happens, you may have:
Numbness or tingling in your fingers and toes.
A poor sense of balance.
Depression.
Dementia, a loss of mental abilities.
Slide88How is vitamin B12 deficiency anemia diagnosed?
Your doctor will examine you and ask questions about your past health and how you are feeling now.
You will also have blood tests to check the number of red blood cells and to see if your body has enough vitamin B12.
The level of folic acid, another B vitamin, will be checked too.
Some people whose vitamin B12 levels are too low also have low levels of folic acid. The two problems can cause similar symptoms. But they are treated differently.
Slide89The health care provider will perform a physical exam. This may reveal problems with your reflexes.
Tests that may be done include:
Complete blood count (CBC)
Reticulocyte
count
Lactate
dehydrogenase
(LDH) level
Vitamin B12 level
Methylmalonic
acid (MMA) level
Other procedures that may be done include:
Esophagogastroduodenoscopy
(EGD) to examine the stomach
Enteroscopy
to examine the small intestine
Bone marrow biopsy if the diagnosis is not clear
TCII
Slide90How is it treated?
Vitamin B12 deficiency
anemia
is treated with supplements of vitamin B12.
Taking supplements brings your level of vitamin B12 back to normal, so you do not have symptoms.
To keep your level of vitamin B12 normal, you will probably need to take supplements for the rest of your life.
If you stop taking them, you'll get
anemia
again.
Slide91Your vitamin B12 supplements might be pills or shots. If you use shots, you can learn to give them to yourself at home.
For many people, pills work just as well as shots.
They also cost less and are easier to take. If you have been getting shots, ask your doctor if you can switch to pills.
Another form of treatment is a vitamin B12 nasal spray (such as
Nascobal
).
Slide92You can take steps at home to improve your health by eating a varied diet that includes meat, milk, cheese, and eggs, which are good sources of vitamin B12.
Also, eat plenty of foods that contain folic acid, another type of B vitamin.
These include leafy green vegetables, citrus fruits, and fortified breads and cereals.
Slide93Can vitamin B12 deficiency
anemia
be prevented?
Most people can prevent this
anemia
by including animal products like milk, cheese, and eggs in their diets.
People who follow a vegan diet can prevent it by taking a daily vitamin pill or by eating foods that have been fortified with B12.
Babies born to who eat a vegan diet should be checked by a doctor to see whether they need extra vitamin B12.
If you have a high risk of getting this type of
anemia
, your doctor can give you vitamin B12 shots or pills to prevent it.
Slide94Treatment depends on the cause of B12 deficiency
anemia
.
The goal of treatment is to increase your vitamin B12 level.
Treatment may include a shot of vitamin B12 once a month. If you have a very low level of B12, you may need more shots in the beginning. It is possible you may need shots every month for the rest of your life.
Some people may also need to take vitamin B12 supplements by mouth.
Treatment may no longer be needed after
Crohn
disease, celiac disease, or alcohol use is properly treated.
Your provider will also recommend that you eat a variety of foods.
Slide95Folate Deficiency
Like B
12
deficiency,
folate
deficiency occurs in stages, with depletion of stores leading to deficiency that can result in
megaloblastic
anemia and other hematologic abnormalities (thrombocytopenia,
leukopenia
).
Treating a B
12
deficiency
megaloblastic
anemia with folic acid may correct the anemia, but does not correct the B
12
deficiency or prevent the development of neurologic changes.
Therefore, it is important to determine the cause of a
megaloblastic
anemia before initiating therapy.
Folate
also is critical in early pregnancy for fetal neural tube development.
To reduce the incidence of neural tube defects, since January 1998 the FDA has required enriched grains to be fortified with folic acid at a concentration that provides, on average, 100 µg per day.
Slide96A high plasma
Hcy
concentration is a risk factor for the development of atherosclerosis, coronary artery disease, stroke, and peripheral vascular disease.
Hyperhomocystinemia
is related to low levels of
folate
and B vitamins.
A
folate
-rich diet as well as folic acid supplementation has been shown to decrease plasma
Hcy
concentrations.
It has been speculated that
folate
replenishment may have an important role in the prevention and treatment of cardiovascular disease.
Slide97Physiologic Importance of
Folate
Reduced forms of
folate
(
tetrahydrofolate
) are cofactors for
transformylation
reactions in the biosynthesis of
purines
and
thymidylates
of nucleic acids.
In
folate
deficiency, reduced
thymidylate
synthesis leads to defective DNA synthesis, resulting in
megaloblast
formation and bone marrow suppression.
Folate
is also involved in the
methylation
cycle and is essential in providing methyl groups for a wide range of cellular
methyltransferases
. In particular,
folate
is needed in
Hcy
metabolism, which accumulates in
folate
deficiency.
Slide98Folate
Needs
Folate
needs depend on metabolic and cell turnover rates. In general, the minimum daily requirement is 65 to 400 µg daily.
In pregnancy, 600 µg daily is recommended, and 500 µg daily for lactating mothers .
More than 2% is degraded daily, so a continuous dietary supply is essential.
The average amount stored in the body is 5 to 10 mg, one half of which is found in the liver.
With
folate
depletion, deficiency leading to anemia generally occurs within 6 months.
Slide99Structure:
Pterdine
Amino
benzoic acid
Gultamic
acid
(
Poly
Glutamic
Acid)
Folicacid
Made of three components.
Folic acid derived from diet is not biologically active.
Once absorbed through the duodenum it hydrolyzed, reduced and methylated to form MTHF.
Other form THF (biologically active).
Slide100Folic Acid
Pteroyl glutamic acid and similar compounds are
termed as folic acid .
Polyglutamate is the
natural form.
Dihydro or tetrahydro folate are
metabolic active forms
.
Slide101Folic acid
Sources :
Produced by plants and some microorganisms
Folate rich foods;
vegetables (Green leaf),
Liver and kidney (parenchymal organs)
Molds.
Slide102Absorption and metabolism
Diet
Intestine
Poly glutamic acid
Poly glutamate
Mono glutamate
CH
3
THF
Methyl Tetrahydrfolate
Glu
Folate reductase
Reduced and methylated
Slide103Circulation
Tissue cell
CH
3
THF
CH
3
THF
Homocysteine
Methionine
cTHF
THF
Glu
DNA
Synthesis
Slide104Causes of folic acid deficiency
The main causes is decrease dietary intake:
Old age,
Alcoholism
Chronic diseases.
Mal absorption:
Tropical sprue.
Gluten-sensitive enteropathy.
Increase requirements:
Pregnancy.
Infancy.
Malignancy.
Drugs:
Methotrexate, oral contraceptives.
Slide105Folate deficiency symptoms
Similar symptoms as B12 save for neurologic symptoms
Presentation is different classically:
Alcoholic
Very poor dietary intake
Older
Depressed
Living alone
Slide106Whom should you test for B12 or Folate deficiency?
MCV >100 with or without anemia
Hypersegmented neutrophils
Pancytopenia of uncertain cause
Unexplained neurologic s/sx
Alcoholics
Malnourished, particularly the elderly
Vegans if no hx of supplementation
Diabetics on metformin with new onset neuropathy
Slide107Lab testing for diagnosis
Serum B12
Serum
Folate
MMA
Homocysteine
Normal
>300
>4
70-270
5-14
Deficiency
<200
<2
Confirm B12
200-300
High
High
Confirm
folate
2-4
Normal
High
Slide108Treatment
The primary prevention of
folate
deficiency should occur through dietary manipulation or oral supplementation.
Pharmacotherapy:
Women planning to become pregnant should take at least 400 µg daily to prevent fetal neural tube defects.
Because many pregnancies are not planned, the FDA has mandated food fortification to enhance the daily
folate
intake in all women by 100 µg daily.
There are two concerns with this approach. One is that the increase in
folate
intake could mask a B
12
deficiency by “correcting” the anemia.
However, one would hope to detect a B
12
deficiency before anemia develops. Also,
folate
dosages of 1 mg or more generally are needed to produce and maintain a remission in a B
12
deficiency anemia.
Slide109The other concern is that the
folate
amount is too low and does not provide enough to prevent neural tube defects.
Therefore, 400 µg folic acid daily is still recommended for pregnant women and women who are trying to become pregnant.
This dosage will also minimize the chance of the women developing
folate
-deficiency anemia during the latter part of the pregnancy, when
folate
needs increase. Dosages less than 1 mg are available in numerous over-the-counter preparations.
Slide110Folate
deficiency usually is treated with oral folic acid 1 mg
daily.This
dose is available only by prescription.
Parenteral
administration is indicated when oral administration is unacceptable (preoperatively, postoperatively, or if nausea or vomiting is a problem) or not possible (
malabsorption
syndromes or after gastric resection).
Available
parenteral
formulations contain 5 mg per milliliter and may be given intramuscularly, subcutaneously, or intravenously
Slide111The duration of therapy depends on the underlying cause.
Replacement therapy should be continued until the underlying problem has been corrected.
If this is impossible, lifelong therapy is needed.
B
12
studies should also be undertaken in people requiring long-term
folate
supplementation.
Long-term therapy may be needed in chronic hemolytic states,
myelofibrosis
, and refractory
malabsorption
.
Postgastrectomy
states, prolonged stress or infection, chronic fever, and persistent diarrhea may also increase needs.
Slide112Monitoring Folate Deficiency Therapy
In anemic patients, treatment response can be monitored by following the
reticulocyte
count, which peaks 5 to 8 days after treatment begins.
Hematologic findings (
Hb
, MCV) should be normal in about 2 months.
Measuring erythrocyte
folate
levels for several months during the treatment can confirm replenishment of tissue stores.
For patients with deficiency without anemia,
folate
stores are replenished in about 3 weeks