Anaemia

INTRODUCTION

Anemia is the blood disorder, characterized by the reduction in:

1. Red blood cell (RBC) count
2. Hemoglobin content
3. Packed cell volume (PVC).
Generally, reduction in RBC count, hemoglobin content and PCV occurs
because of:
1. Decreased production of RBC
2. Increased destruction of RBC
3. Excess loss of blood from the body.
 All these incidents are caused either by inherited disorders or
environmental influences such as nutritional problem, infection and
exposure to drugs or toxins.
CLASSIFICATION OF ANEMIA

Anemia is classified by two methods:

1. Morphological classification
2. Etiological classification.

„MORPHOLOGICAL CLASSIFICATION

Morphological classification depends upon the size and color of RBC.

Size of RBC is determined by mean corpuscular volume (MCV). Color is
determined by mean corpuscular hemoglobin concentration (MCHC). By
this method, the anemia is classified into four type
1. Normocytic Normochromic Anemia
 Size (MCV) and color (MCHC) of RBCs are normal. But the number of
RBC is less.
2. Macrocytic Normochromic Anaemia
 RBCs are larger in size with normal colour. RBC count is less.
3. Macrocytic Hypochromic Anaemia
 RBCs are larger in size. MCHC is less, so the cells are pale (less
coloured).
4. Microcytic Hypochromic Anaemia
 RBCs are smaller in size with less colour.
ETIOLOGICAL CLASSIFICATION
On the basis of etiology (study of cause or origin), anaemia is divided
into five types
1. Hemorrhagic anaemia
2. Hemolytic anaemia
3. Nutrition deficiency anaemia
4. Aplastic anaemia
5. Anaemia of chronic diseases
 Nutrition Deficiency
Anemia

Anemia that occurs due to deficiency of a nutritive

substance necessary for erythropoiesis is called
nutrition deficiency anemia. The substances which
are necessary for erythropoiesis are iron, proteins and
vitamins like C, B12 and folic acid. The types of
nutrition deficiency anemia are:
Iron deficiency anemia

Iron deficiency anemia is the most common type of anemia. It develops due to
inadequate availability of iron for hemoglobin synthesis. RBCs are microcytic and
hypochromic.

 Causes of iron deficiency anemia:

i. Loss of blood

ii. Decreased intake of iron

iii. Poor absorption of iron from intestine

iv. Increased demand for iron in conditions like growth and pregnancy.
STAGES OF IRON DEFICIENCY

The progression to iron deficiency can be divided into three stages

 The first stage is negative iron balance, in which the demands for
(or losses of) iron exceed the body’s ability to absorb iron from the
diet. This stage results from a number of physiologic mechanisms,
including blood loss, pregnancy (in which the demands for red cell
production by the fetus outstrip the mother’s ability to provide iron),
rapid growth spurts in the adolescent, or inadequate dietary iron
intake.
Iron-deficient erythropoiesis

 marrow iron stores are absent when the serum ferritin level is <15
μg/L. As long as the serum iron remains within the normal range,
hemoglobin synthesis is unaffected despite the dwindling iron stores.
Once the transferrin saturation falls to 15–20%, hemoglobin synthesis
becomes impaired. This is a period of iron-deficient erythropoiesis
 Gradually, the hemoglobin begins to fall, reflecting iron-deficiency
anemia.
The transferrin saturation at this point is <10–15%.
CLINICAL PRESENTATION OF IRON DEFICIENCY

Certain clinical conditions carry an increased likelihood of iron deficiency.

Pregnancy, adolescence, periods of rapid growth, and an intermittent
history of blood loss of any kind should alert the clinician to possible iron
deficiency. A cardinal rule is that the appearance of iron deficiency in an
adult male or postmenopausal female means gastrointestinal blood loss
until proven otherwise.
 Signs related to iron deficiency depend on the severity and chronicity
of the anemia in addition to the usual signs of anemia—fatigue,
pallor, and reduced exercise capacity. Cheilosis (fissures at
the corners of the mouth) and koilonychia (spooning of the
fingernails) are signs of advanced iron deficiency. The
diagnosis of iron deficiency is typically based on laboratory results
LABORATORY IRON STUDIES

 Serum Iron and Total Iron-Binding Capacity

 Serum Ferritin
 Evaluation of Bone Marrow Iron Stores
 Serum Levels of Transferrin Receptor Protein
TREATMENT

 Younger individuals who have compensated for their anemia can be

treated more conservatively with iron replacement. The foremost
issue for the latter patient is the precise identification of the cause of
the iron deficiency.

For the majority of cases of iron deficiency (pregnant women, growing

children and adolescents, patients with infrequent episodes of bleeding,
and those with inadequate dietary intake of iron), oral iron therapy will
sufficent.
 For patients with unusual blood loss or malabsorption, specific
diagnostic tests and appropriate therapy take priority. Once the
diagnosis of iron-deficiency anemia and its cause is made, there are
three major therapeutic approaches.
RED CELL TRANSFUSION

Transfusion therapy is reserved for individuals who have symptoms of

anemia, cardiovascular instability, and continued and excessive blood
loss from whatever source and who require immediate intervention. The
management of these patients is less related to the iron deficiency than
it is to the consequences of the severe anemia. Not only do transfusions
correct the anemia acutely, but the transfused red cells provide a source
of iron for reutilization, assuming they are not lost through continued
bleeding.
ORAL IRON THERAPY

 In the asymptomatic patient with established iron-deficiency anemia and an

intact gastrointestinal tract, treatment with oral iron is usually adequate.
Encouraging dietary intake of iron-rich foods is also useful. Such foods include
oysters, kidney beans, beef liver, tofu, beef (chuck roast, lean ground beef),
turkey leg, whole-wheat bread, tuna, eggs, shrimp, peanut butter, leg of lamb,
brown rice, raisin bran (whole grain–enriched cereals), lentils, and beans.
Multiple preparations of oral iron supplements are available, ranging from simple
iron salts to complex iron compounds designed for sustained release throughout
the small intestine.
PARENTERAL IRON THERAPY

 Intravenous iron can be given to patients who are unable to tolerate

oral iron; whose needs are relatively acute; or who need iron on an
ongoing basis, usually due to persistent gastrointestinal or menstrual
blood loss.

 Parenteral iron is used in two ways: one is to administer the total

dose of iron required to correct the hemoglobin deficit and provide
the patient with at least 500 mg of iron stores; the second is to give
repeated small doses of parenteral iron over a protracted period
Protein deficiency anemia

 Due to deficiency of proteins, the synthesis of hemoglobin is reduced. The

RBCs are macrocytic and hypochromic.

Pernicious anemia or Addison’s anemia

 Pernicious anemia is the anemia due to deficiency of vitamin B12. It is also

called Addison’s anemia. It is due to atrophy of the gastric mucosa because
of autoimmune destruction of parietal cells. The gastric atrophy results in
decreased production of intrinsic factor and poor absorption of vitamin B12,
which is the maturation factor for RBC.
Megaloblastic anemia

 Megaloblastic anemia is due to the deficiency of another maturation

factor called folic acid. Here, the RBCs are not matured. The DNA
synthesis is also defective, so the nucleus remains immature. The
RBCs are megaloblastic and hypochromic.
Causes of folate deficiency

 Diet
1. Poor intake of vegetables
2. Malabsorption
• e.g. Coeliac disease, small bowel surgery
3. Increased demand
- Cell proliferation, e.g. haemolysis
- Pregnancy
Drugs
 Certain anticonvulsants (e.g. phenytoin)
 Contraceptive pill
 Certain cytotoxic drugs (e.g. methotrexate)
Symptoms

• Malaise
• Breathlessness
• Paraesthesia
• Sore mouth
• Weight loss
• Impotence
• Poor memory
• Depression
• Personality change
• Hallucinations
• Visual disturbance
Signs

 Smooth tongue
 Angular cheilosis
 Vitiligo
 Skin pigmentation
 Heart failure
 Pyrexia
Management of megaloblastic
anaemia
 The treatment should always include both folic acid and vitamin B12.
The use of folic acid alone in the presence of vitamin B12 deficiency
may result in worsening of neurological features.

 Vitamin B12 deficiency

Vitamin B12 deficiency is treated with hydroxycobalamin. In cases of

uncomplicated deficiency, 1000 μg IM for 6 doses 2 or 3 days apart,
followed by maintenance therapy of 1000 μg every 3 months for life, is
recommended.
 Folate deficiency

Oral folic acid (5 mg daily for 3 weeks) will treat acute deficiency and 5
mg once weekly is adequate maintenance therapy. Prophylactic folic
acid in pregnancy prevents megaloblastosis in women at risk, and
reduces the risk of fetal neural tube defects. Prophylactic
supplementation is also given in chronic hematological disease
associated with reduced red cell lifespan (e.g. haemolytic anaemias).
Haemorrhagic Anaemia

 Hemorrhage refers to excessive loss of blood . Anemia due to

hemorrhage is known as hemorrhagic anemia. It occurs both in acute
and chronic hemorrhagic conditions.
Acute hemorrhage
 Acute hemorrhage refers to sudden loss of a large quantity of blood
as in the case of accident. Within about 24 hours after the
hemorrhage, the plasma portion of blood is replaced. However, the
replacement of RBCs does not occur quickly and it takes at least 4 to
6 weeks. So with less number of RBCs, hemodilution occurs. However,
morphologically the RBCs are normocytic and normochromic.
Decreased RBC count causes hypoxia, which stimulates the bone
marrow to produce more number of RBCs. So, the condition is
corrected within 4 to 6 weeks.
Chronic hemorrhage

 It refers to loss of blood by internal or external bleeding, over a long

period of time. It occurs in conditions like peptic ulcer, purpura,
hemophilia and menorrhagia. Due to continuous loss of blood, lot of
iron is lost from the body causing iron deficiency. This affects the
synthesis of hemoglobin resulting in less hemoglobin content in the
cells. The cells also become small. Hence, the RBCs are microcytic
and hypochromic.
Treatment
 Stopping bleeding
 Usually iron supplements

For large or rapid blood loss, the source of bleeding must be found and the bleeding
stopped. Transfusion of red blood cells may be needed.

With slow or small blood loss, the body may produce enough red blood cells to correct
the anemia without the need for blood transfusions once the bleeding is stopped.

Because iron, which is required to produce red blood cells, is lost as a result of
bleeding, most people who have anemia due to bleeding need to take iron
supplements, usually tablets, for several months. Sometimes people are given iron
intravenously.
anemia of inflammation and chronic
disease
 Anemia of inflammation and chronic disease is a
type of anemia that commonly occurs with chronic,
or long term, illnesses or infections. Cancer and
inflammatory disorders, in which abnormal
activation of the immune system occurs, can also
cause AI/ACD.
 AI/ACD is easily confused with iron deficiency
anemia because in both forms of anemia levels of
iron circulating in the blood are low. Iron in the body
is found both circulating in the blood and stored in
body tissues. Circulating iron is necessary for red
blood cell production. Low blood iron levels occur in
iron-deficiency anemia because levels of the iron
stored in the body’s tissues are depleted.
 In AI/ACD, however, iron stores are normal or high.
Low blood iron levels occur in AI/ACD, despite
normal iron stores, because inflammatory and
chronic diseases interfere with the body’s ability to
use stored iron and absorb iron from the diet.
AI/ACD is the second most common form of anemia,
after iron-deficiency anemia
 Who gets AI/ACD?

While AI/ACD can affect people at any age, older

adults are especially at risk because they have the
highest rates of chronic disease. AI/ACD is also
common among hospitalized patients, particularly
those with chronic illnesses.
What causes AI/ACD?

Anemia of inflammation and chronic disease is caused by red

blood cells not functioning normally, so they cannot absorb and
use iron efficiently. In addition, the body cannot respond normally
to erythropoietin (EPO), a hormone made by the kidneys that
stimulates bone marrow to produce red blood cells. Over time,
this abnormal functioning causes a lower than normal number of
red blood cells in the body. Some of the chronic diseases that
lead to AI/ACD include infectious and inflammatory diseases,
kidney disease, and cancer. Certain treatments for chronic
diseases may also impair red blood cell production and
contribute to AI/ACD.
 Infectious diseases that cause AI/ACD include,

• tuberculosis, an infection in the lungs

• HIV/AIDS, an infection that destroys the immune system
• endocarditis, an infection in the heart
• osteomyelitis, a bone infection
 Inflammatory diseases that can lead to AI/ACD include

•Rheumatoid arthritis, which causes pain, swelling, stiffness, and

loss of function in the joints.

• Lupus, which causes damage to various body tissues, such as

the joints, skin, kidneys, heart, lungs, blood vessels, and brain
SYMPTOMS

 Anemia of inflammation and chronic disease typically develops

slowly and, because it is usually mild, may cause few or no
symptoms. Symptoms of anemia may also be masked by the
symptoms of the underlying disease. Sometimes, AI/ACD can
cause or contribute to

• fatigue
• weakness
• pale skin
• a fast heartbeat
• shortness of breath
• exercise intolerance
Treatment

 Anemia of inflammation and chronic disease often is not

treated separately from the condition with which it occurs. In
general, health care providers focus on treating the underlying
illness. If this treatment is successful, the anemia usually
resolves. For example, antibiotics prescribed for infection and
anti-inflammatory medications prescribed for rheumatoid
arthritis or IBD can cause AI/ACD to disappear. However,
AI/ACD is increasingly being viewed as a medical condition
that merits direct treatment.
 If iron deficiency has a role in causing AI/ACD, a person may
need iron supplements to raise hematocrit to a target level. Iron
supplements can be taken by pill, subcutaneously, or
intravenously during hemodialysis.

 People with kidney disease and AI/ACD may also be advised to

take vitamin B12 and folic acid supplements. A person should
talk with a health care provider before taking any supplements
 Hemolytic Anemia

Hemolysis means destruction of RBCs. Anemia due to excessive

hemolysis which is not compensated by increased RBC production is
called hemolytic anemia. It is classified into two types:
A. Extrinsic hemolytic anemia.
B. Intrinsic hemolytic anemia.
 Extrinsic hemolytic anemia:

It is the type of anemia caused by destruction of RBCs by external

factors. Healthy RBCs are hemolized by factors outside the blood cells
such as antibodies, chemicals and drugs. Extrinsic hemolytic anemia is
also called autoimmune hemolytic anemia.

Common causes of external hemolytic anemia:

 i. Liver failure
 ii. Renal disorder
iii. Hypersplenism
iv. Burns
v. Infections like hepatitis, malaria and septicemia
vi. Drugs such as penicillin, antimalarial drugs and sulfa drugs
vii. Poisoning by chemical substances like lead, coal and tar
viii. Presence of isoagglutinin like anti­Rh
ix. Autoimmune diseases such as rheumatoid arthritis and
ulcerative colitis
Intrinsic hemolytic anemia:

It is the type of anemia caused by destruction of RBCs because of

the defective RBCs. There is production of unhealthy RBCs, which
are short lived and are destroyed soon. Intrinsic hemolytic
anemia is often inherited and it includes sickle cell anemia and
thalassemia. Because of the abnormal shape in sickle cell anemia
and thalassemia, the RBCs become more fragile and susceptible
for hemolysis.
Sickle cell anemia

Sickle cell anemia is an inherited blood disorder, characterized by sickle­shaped

red blood cells. It is also called hemoglobin SS disease or sickle cell disease. It is
common in people of African origin. Sickle cell anemia is due to the abnormal
hemoglobin called hemoglobin S (sickle cell hemoglobin). In this, α­chains are
normal and β­chains are abnormal. The molecules of hemoglobin S polymerize
into long chains and precipitate inside the cells. Because of this, the RBCs attain
sickle (crescent) shape and become more fragile leading to hemolysis.
Thalassemia

 Thalassemia is an inherited disorder, characterized by abnormal

hemoglobin. It is also known as Cooley’s anemia or Mediterranean
anemia. It is more common in Thailand and to some extent in
Mediterranean countries.
 Thalassemia is of two types:
i. α ­thalassemia
ii. β ­thalassemia.
The β­thalassemia is very common among these two. In normal
hemoglobin, number of α and β polypeptide chains is equal. In
thalassemia, the production of these chains become imbalanced
because of defective synthesis of globin genes. This causes the
precipitation of the polypeptide chains in the immature RBCs, leading to
disturbance in erythropoiesis. The precipitation also occurs in mature red
cells, resulting in hemolysis.
α-Thalassemia

 α­thalassemia occurs in fetal life or infancy. In this α­chains are less,

absent or abnormal. In adults, β­chains are in excess and in children, γ­
chains are in excess. This leads to defective erythropoiesis and
hemolysis. The infants may be stillborn or may die immediately after
birth.
β-Thalassemia
 In β­thalassemia, β­chains are less in number, absent or abnormal with
an excess of α­chains. The α­chains precipitate causing defective
erythropoiesis and hemolysis
Extravascular haemolysis
 Physiological red cell destruction occurs in the reticulo-endothelial cells
in the liver or spleen, so avoiding free hemoglobin in the plasma. In
most hemolytic states, hemolysis is predominantly extravascular.

Intravascular haemolysis
 Less commonly, red cell lysis occurs within the blood stream due to
membrane damage by complement (ABO transfusion reactions,
paroxysmal nocturnal haemoglobinuria), infections (malaria, Clostridium
perfringens), mechanical trauma (heart valves, DIC) or oxidative
damage (e.g. enzymopathies such as glucose-6-phosphate
dehydrogenase deficiency, which may be triggered by drugs such as
dapsone and Malo prim).
Symptoms and Signs of Hemolytic Anemia

 Systemic manifestations of hemolytic anemias resemble those of

other anemias and include pallor, fatigue, dizziness, and weakness.
Scleral icterus and/or jaundice may occur, and the spleen may
enlarge. Thrombosis increases with many forms of hemolytic anemia.

 Hemolytic crisis (acute, severe hemolysis) is uncommon; it may be

accompanied by chills, fever, back and abdominal pain, and shock.
Hemoglobinuria causes red or reddish-brown urine.
diagnosis

 Peripheral smear and reticulocyte count

 Serum bilirubin (indirect), lactic dehydrogenase (LDH), and
haptoglobin
 Sometimes antiglobulin (Coombs) test and/or hemoglobinopathy
screen
 Urinalysis

Hemolysis is suspected in patients with anemia and reticulocytosis. If

hemolysis is suspected, a peripheral smear is examined and serum
bilirubin, LDH, and haptoglobin are measured. The peripheral smear and
reticulocyte count are the most important tests to diagnose hemolysis.
Antiglobulin testing or hemoglobinopathy screening (eg, high-
performance liquid chromatography [HPLC]) can help identify the cause
of hemolysis based on the results of the above laboratory investigations.
Treatment of Hemolytic Anemia

 Treatment depends on the specific mechanism of hemolysis.

 Corticosteroids are helpful in the initial treatment of warm antibody

autoimmune hemolysis. Transfusions are used in patients with
symptomatic anemia or when there is reticulocytopenia.

 Splenectomy is beneficial in some situations, particularly when

splenic sequestration is the major cause of RBC destruction. If
possible, splenectomy is delayed until 2 weeks after vaccination with
the following:
 Pneumococcal vaccine

 Hemophilus influenzae vaccine

 Meningococcal vaccine

 In cold agglutinin disease, avoidance of cold is recommended, and

blood will need to be warmed before transfusion. Folate replacement
is needed for patients with ongoing long-term hemolysis
Aplastic anemia

Aplastic anemia is a disease of the bone marrow that occurs when the
bone marrow stops producing enough new blood cells. Bone marrow is a
sponge-like tissue inside the bones that makes stem cells that develop
into red blood cells, white blood cells, and platelets.
Causes

 Aplastic anemia is caused by destruction of the blood-forming stem

cells in a person’s bone marrow. Most research suggests that stem
cell destruction occurs because the body’s immune system attacks its
own cells by mistake. Normally, the immune system attacks only
foreign substances. When the immune system attacks one’s own
body, it is known as an autoimmune disease; aplastic anemia is
generally thought to be an autoimmune disease.
 Low red blood cell count: The most common symptom of a low red
blood cell count is fatigue. A low red blood cell count also can cause
shortness of breath; dizziness, especially when standing up;
headaches; coldness in hands or feet; pale skin; and chest pain.

 Low white blood cell count: Also called neutropenia, a low white
blood cell count can increase the risk for infections.

 Low platelet count: A low platelet count, also called

thrombocytopenia, can lead to bleeding problems and cause a person
to bruise easily.
Investigations

 Blood Tests When trying to figure out the cause of a person’s

symptoms, the doctor will ask for blood samples. These samples will
be used in a number of tests, including:
 A complete blood count (CBC) test to measure the number of each
blood cell type in a person’s blood sample
 A reticulocyte count to measure the number of young red blood cells
in a person’s blood
 An EPO, or erythropoietin, count. EPO is a protein made in a person’s
kidneys that causes the bone marrow to make more red blood cells
 Iron level measurements
 • Vitamin B-12 and folate levels
 Bone Marrow Examination , a pathologist will take a bone marrow
sample from the hip bone to examine.
Treatment

 Supportive care, or treatments that help to manage the symptoms

of aplastic anemia and is not a cure. This approach includes the use
of blood transfusions, iron chelation therapy to treat iron overload,
growth factors, and antibiotics.

 Immunosuppressive drug therapy lowers the body’s immune

response to prevent one’s immune system from attacking the bone
marrow, let stem cells grow back, and raise blood counts. In acquired
aplastic anemia, immunosuppressive therapy with anti-thymocyte
globulin (ATG) plus cyclosporine is the therapy of choice for older
patients and patients who do not have a matched stem cell donor.
 Stem cell transplantation replaces damaged stem cells with
healthy ones from another person (a donor). During the transplant,
which is similar to a blood transfusion, a person gets donated stem
cells through a tube placed in a vein in the chest. The stem cells
travel to the bone marrow and begin making new blood cells. Stem
cell transplants may cure aplastic anemia in people who are eligible
for this type of treatment. The transplant works best in children and
young adults with severe aplastic anemia who are in good health and
who have matched donors, while older people may be less able to
handle the treatments needed to prepare the body for the transplant.