ANEMIA

Dr. Feisal Dahir Kahie, MD

Mmed Internal Medicine
KIU-Western Campus
DEFINITION
 Deficiency in the number of erythrocytes(RBC),

the quantity of hemoglobin and/or the volume

of packed RBCs
CLASSIFICATION

 Etiologic (underlying cause)

 Morphologic (cellular characteristic)

 Classification based on signs and symptoms

ETIOLOGIC CLASSIFICATION
 Decreased erythrocyte production

 Blood loss

 Increased erythrocyte destruction

DECREASED ERYTHROCYTE PRODUCTION
 Decreased hemoglobin synthesis
* Iron deficiency
* Thalassemia(decreased globin synthesis)

 Defective DNA synthesis

* Cobalamin deficiency
* Folic acid deficiency

 Decreased number of erythrocyte precursors

* Aplastic anemia
* Anemia of myeloproliferative diseases(leukemia)
BLOOD LOSS
 Acute
* Trauma
* Blood vessel rupture

 Chronic
* Gastritis
* Hemorrhoids
* Menstrual flow
INCREASED ERYTHROCYTE
DESTRUCTION
 Abnormal hemoglobin( Sickle cell anemia)

 Infectious agents

 Physical trauma
MORPHOLOGIC CLASSIFICATION
 Normocytic normochromic

 Macrocytic normochromic

 Microcytic hypochromic
CLASSIFICATION BASED ON
SIGNS AND SYMPTOMS

 Mild

 Moderate

 severe
NORMOCYTIC NORMOCHROMIC
 Normal size and colour

 Causes include acute blood loss, chronic

kidney disease, aplastic anemia, sickle cell
anemia
MACROCYTIC NORMOCHROMIC
 Large size normal colour

 Causes include cobalamin deficiency, folic

acid deficiency, liver disease, post
splenectomy
MICROCYTIC HYPOCHROMIC
 Small size pale colour

 Causes include iron deficiency anemia,

Thalassemia
BASED ON THE CLINICAL
MANIFESTATIONS
 Mild(Hb- 10-14gm/dl)
* cardiovascular: palpitations
* Pulmonary : Exertional dyspnea

 Moderate (Hb- 6- 10 gm/dl)

* Cardiovascular: Increased palpitations
* Pulmonary: Dyspnea
* General: Fatigue
BASED ON THE CLINICAL
MANIFESTATIONS….
 Severe(Hb- less than 6gm/dl)
* Integumentary: Pallor, pruitus
* Eyes: Icteric conjuctiva and sclera,
blurred vision
* Mouth: Glossitis, Smooth tongue
* Cardiovascular: Tachycardia,
increased pulse pressure, murmurs
* Pulmonary: tachypnea, orthopnea,
dyspnea at rest
SEVERE….
* Neurologic: Headache, Vertigo,
irritability, depression, impaired thought
process

* Gastro intestinal: Anorexia,

hepatomegaly, splenomegaly, difficulty in
swallowing, sore mouth

* Musculo skeletal: Bone pain

* General : sensitivity to cold, weight loss

and lethargy
 ANEMIA CAUSED BY DECREASED
ERYTHROCYTE PRODUCTION
 Decreased Hb synthesis Iron deficiency anemia,
Thalassemia

 Defective DNA synthesis in RBC megaloblastic

anemia

 Diminished availability of erythrocyte precursors

Aplastic anemia, anemia of chronic disease
IRON DEFICIENCY ANEMIA
 Normal iron metabolism
 Obtained from food and dietary supplements

 Ingested iron absorbed in the duodenum and

upper jejunum

 Iron present in all RBC as heme in

hemoglobin and in a stored form(ferritin and
hemosiderin) in the bone marrow, spleen,
liver and macrophages
DAİLY IRON DEMANDS
 Male 1 mg

 Adolesc. 2-3 mg

 Women in repr.age 2-3 mg

 Pregnant 3-4 mg
 Small loss of iron each day in urine, faeces,
skin and in menstruating females as blood (1-2
mg daily)

 Normal diet contains about 15 mg of

iron/day

 6mg elemental iron/1000 cal

 1/10 of ingested iron is absorbed

 Gastric acid releases iron from food

DEFINITION
 Iron deficiency anemia is defined as anemia
associated with either inadequate absorption
or excessive loss of iron from the body.
ETIOLOGY
 Inadequate dietary intake
 Malabsorption

* After certain types of gastro intestinal

surgery(removal of bypass of duodenum)

* Malabsorption syndromes(diesases of the

duodenum)
ETIOLOGY…
 Blood loss

* sources of chronic blood loss are from GI

and GU systems
* Causes of GI blood loss – peptic ulcer,
gastritis, esophagitis, hemorrhoids and
neoplasms
* causes of GU blood loss – menstrual
bleeding
* At the time of delivery and lactation
ETIOLOGY…
 Pregnancy
- Diversion of iron to the fetus for
erythropoiesis

 Dialysis treatment
- blood lost in the dialysis equipment and
frequent blood sampling
CLINICAL MANIFESTATIONS
 Fatigability
 Dizziness
 Headache
 Irritability
 palpitation
 Glossitis
 Stomatitis
 Dry pale skin
 Spoon shaped nails, koilonychia
 Hair loss
 Splenomegaly
DIAGNOSTIC MEASURES
 Hb,Hct,RBC:Low

 Plt:Normal/Low/High

 WBC:Normal/Low

 S iron: Decreased
DIAGNOSTIC MEASURES….
 History collection and physical examination

 Stool routine: to identify the presence of

blood

 Endoscopy or colonoscopy: used to detect GI

bleeding
TREATMENT
 Replace iron and folic acid and treat
underlying disease.

 Oral route is preferred for replacement.

 Intake of liver and muscle meats, eggs, dried

fruits, legumes, dark green leafy vegetables,
bread and cereals and potatoes

 If iron deficiency from acute blood loss require

transfusion of packed RBC
TREATMENT….
 Response can be followed by retic.
increase in 1-2 weeks (5-7 days)

 Hb response to treatment
 half normal by a month
 returns to normal by 2-4 months

 Replacement therapy is prolonged by 6-12

months to replenish stores of iron.

 Ongoing bleeding may cause indefinite

therapy.
TREATMENT….
DRUG THERAPY
 Oral iron is usually prescribed

 Total daily dose:150-200 mg elemental iron

 Give in 3-4 divided doses(each tablet contains 50

to100mg of iron)

 Each one hour before meals.

 Taking iron with Vit C enhances iron

absorbtion
TREATMENT…
 Undiluted liquid iron may stain patients
teeth, therefore diluted and ingested
through a straw

 Iron preparations cause the stools to become

black(GI tract excretes excess iron)

 Constipation is common, therefore started on

stool softeners
TREATMENT…
 Parenteral iron therapy:
Indications
 Malabsorbtion

 Intolerance to oral replacement

 Colitis/enteritis

 Needs in excess of amount that can be given

orally

 Patient uncooperative/poor compliance

 Hemodialysis
TREATMENT…
Parenteral iron therapy:
 Given intramuscularly or intravenously

 Iron dextran complex contains 50mg/ml of

elemental iron in 2ml

 Test dose of parenteral iron is often done to

assess for allergic reaction

 Given deep IM in the outer quadrant of the

buttocks with a 18 to 20 gauze needle
THALASSEMIA
 Group of diseases that have an autosomal
recessive genetic basis involving inadequate
production of normal hemoglobin
 Normal hemoglobin is composed of 2 alpha and 2
beta globins
 Mutations in a given globin gene can cause a
decrease in production of that globin, resulting
in deficiency
 Absence of alpha globin chain alpha
thalassemia
 Absence of beta globin chain beta thalassemia
 CLINICAL MANIFESTATIONS
 Growth both physical and mental is retarded
Person with thalassemia major is pale and
displays other symptoms of anemia( Inadequate
production + ineffective erythropoiesis + haemolysis
Anaemia)

 Symptoms develop in childhood by 2 years of age

 Pronounced hepatosplenomegaly
(↑Haemolysis ↑demands of phagocytic function
 hyperplasia of phagocytes 
Hepatosplenomegaly )
CLINICAL MANIFESTATIONS….
 To compensate anaemia extramedullary
haemopoiesis in liver, spleen & brain
Organomegaly

 ↑Erythropoiesis marrow expansion & thinning of

cortex of skull bone Thalassaemia facies

 Jaundice from RBC hemolysis

DIAGNOSTIC MEASURES
 Hb concentration – Decreased

 ESR – Mild increase

 RBC count – Markedly decreased

 Reticulocyte count – Increased

TREATMENT
 Thalassemia minor requires no treatment
 Treatment of thassemia major includes
 Chronic Transfusion Therapy
 Maximizes growth and development
 Suppresses the patient’s own ineffective
erythropoiesis and excessive dietary iron absorption
 RBC transfusions often monthly to maintain Hgb 10-
12
 Chelation Therapy
 Binds free iron and reduces hemosiderin
deposits
 8-hour subcutaneous infusion of deferoxamine,
5 nights/week
 Start after 1year of chronic transfusions
 Splenectomy--indications
 Trasfusion requirements increase 50% in
6months
 Severe leukopenia or thrombocytopenia
MEGALOBLASTIC ANEMIA/COBALAMINE
DEFICIANCY ANEMIA
 Group of disorders caused by impaired DNA
synthesis and characterized by the presence of
large RBC

 Impaired DNA synthesis defective RBC

maturation

 Large (macrocytic) and abnormal RBC

megaloblasts
ETIOLOGY
 Result from cobalamin (Vit B12) and folic
acid deficiencies
 Supression of DNA synthesis by
* drugs

* inborn errors of cobalamin and folic acid

metabolism

* erythroleukemia( malignanat blood

disorder characterized by proliferation of
erythropoietic cells in bone marrow)
COBALAMIN (VIT B12 )
DEFICIENCY
 Vitamin B12
 Sources : Meat, fish

 Daily requirement : 2-5 micro gram

 Body stores : 3-5 mg( liver)

 Places of absorption: distal ileum

ETIOLOGY
1.Malabsorption
a) Inadequate production of intrinsic factor
- pernicious anemia
- gastrectomy, partial or total

b) Inadequate releasing vit. B12 from food

(partial gastrectomy, abnormality of
stomach function, chronic pancreatic
insufficiency)
MALABSORPTION…
c) Terminal ileum disease (celiac disease, ileal
resection, Crohn disease)

d) Competition for intestinal B12 :

- bacterial overgrowth: jejunal
diverticula, intestinal stasis and obstruction due
to strictures
- Fish tapeworm
ETIOLOGY….
2. Inadequate intake
- vegetarians

3. Inadequate utilisation
Drugs: Neomycin, Colchicin, Nitrous oxide ,long
term use of H2 receptor blockers
CLINICAL MANIFESTATIONS
 Atrophic glossitis (shiny tongue)

 Abnormal gait

 Anemia related manifestations

 Personality changes

 Anorexia

 Nausea, vomiting

 Abdominal pain
CLINICAL MANIFESTATIONS…
Neurologic manifestations
 Paresthesias

 Memory loss
 Numbness

 Weakness

 Symmetric neuropathy legs>arms

 Severe weakness, spasticity, paraplegia and incontinence
 Subacute combined degeneration of the dorsal
(posterior) and lateral spinal columns
DIAGNOSTIC MEASURES
1. Blood cell count:
macrocytic anemia
Thrombocytopenia
leucopenia (granulocytopenia)
low reticulocyte count
2. Blood smear:
Hypersegmentation of granulocytes
DIAGNOSTIC MEASURES….
3. Bone marrow smear
Hypercellular
Erythroid cell changes (megaloblasts,
RBC precursor a abnormally large with
nuclear- cytoplasmic asynchrony)

Megakaryocytes are decreased and show

abnormal morphology
TREATMENT
 If the patient has
dietary deficiency
of cobalamin
dietary sources
rich in cobalamin
should be provided
TREATMENT….
1. Vitamin B12 administration intramuscular in dose 1000
μg per day for a week , then 100 μg 2x per week for 2
weeks, 1 x per week 100μg for month

2. Reticulocytosis begins 2 or 3 days after therapy

started and maximal number reached on day 5 to 8.
* Serum iron monitoring, after 7-10 days of vit.B12
treatment,
* if Fe deficiency is diagnosed, start iron substitution

3. 100 ug vit.B12 i.m. every month, regimen that must be

mainted for the rest on the patients life.
FOLIC ACID DEFICIENCY
 Folic acid deficiency Megaloblastic
anemia

 Folic acid is required for DNA synthesis,

leading to RBC formation and maturation
FOLIC ACID

Sources : Green vegetables, yeast

Daily requirement :50-100 ug

Body stores :10-12mg (liver)

Places of absorption : duodenum and proxymal

segment of small intestine
 ETIOLOGY
1. Inadequate intake
- diet lacking leafy green vegetables, liver,
citrus fruits, dried beans, nuts and grains;
chronic alcoholism, total parenteral nutrition

2. Malabsorption
- small bowel disease ( celiac disease)
- alcoholism
ETIOLOGY….
3. Increased requirements:
- pregnancy and lactation
- infancy
- chronic hemolysis
- malignancy
- hemodialysis

4. Defective utilisation
Drugs:folate antagonists(methotrexate,
trimethoprim), purine analogs (azathioprine),
primidine analogs (zidovudine), RNA reductase
inhibitor (hydroxyurea), miscellaneous
(phenytoin)
CLINICAL MANIFESTATIONS
 Clinical features similar to those of
cobalamin deficiency

 GI disturbances include dyspepsia and a

smooth red tongue

 Absence of neurologic problem

DIAGNOSTIC MEASURES
 Hemoglobin – Decreased

 S. Folate level - Low

TREATMENT
 Treated by replacement therapy

1. Oral administration of folate 1 (5) mg per

day, for 3 months, and maintance therapy if
it’s necessary.

2. Reticulocytosis after 5-7 days

3. Correction of anemia is over after 1-2

months of therapy
TREATMENT…
 Eat foods
containing large
amounts of folic
acid
ANEMIA OF CHRONIC DISEASE
 Chronic inflammatory, autoimmune,
infectious, or malignant diseases can lead to
anemia and it is known as anemia of chronic
disease

 Associated with under production of RBC and

shortening of RBC survival
ETIOLOGY
Chronic conditions leading to anemia

 Renal diseases

 Autoimmune hemolysis

 Chemotherapy and radiation therapy

 Infections

 Hypopitutirism & Hypothyroidism

DIAGNOSTIC MEASURES
 Findings of elevated serum ferritin and
increased iron stores distinguish it from iron
deficiency anemia.

 Normal folate and cobalamin blood levels

distinguish it from those types of anemias.
MANAGEMENT
 Correction of the underlying disorder

 Blood transfusions

 Erythropoetin therapy(Epogen, Procit)

APLASTIC ANEMIA
 Rare disease caused by a decrease in or
damage to marrow stem cells, damage to
the microenvironment within the marrow,
and replacement of the marrow with fat.
It results in bone marrow aplasia
(markedly reduced hematopoiesis).
APLASTIC ANEMIA

 Characterized by peripheral blood

pancytopenia( decrease of all blood types-
RBCs, white blood cells and platelets)
 ETIOLOGY
Congenital causes
 Fanconi syndrome( disease of the proximal renal
tubules in which glucose, uric acid and amino acids
are not absorbed properly)

 Congenital dyskeratosis( abnormal pigmentation of

the skin will occur)

 Amegakaryocytic thrombocytopenia( it’s a

hematological disease characterized by severe
thrombocytopenia due to altered immunological
status)
ETIOLOGY….
Acquired causes

 Exposure to ionizing radiation

 Chemotherapy
 Chemical agents( benzene, arsenic, alcohol)
 Viral and bacterial infections
 Medications( Anti seizure agents, anti
microbials)
CLINICAL MANIFESTATIONS
 General manifestations of anemia( fatigue,
dyspnea along with cardiovascular and
neurologic responses)

 Patient with neutropenia susceptible to

infection and may be febrile

 Thrombocytopenia is manifested by a
predisposition to bleeding( petechiae,
epistaxis)
DIAGNOSTIC MEASURES
 Decreased Hb, WBC, and platelet values

 Normocytic, normochromic anemia.

 Low reticulocyte count.

 Prolonged Bleeding time .

 Elevated serum iron and total iron-binding

capacity (TIBC)

 Bone marrow biopsy - hypocellular with increased

yellow marrow (fat content).
MANAGEMENT
 Identify and remove the causative agent

 Hematopoietic stem cell transplant and

immuno suppressive therapy with anti
thymocyte globulin(ATG) and cyclosporine or
high dose cyclo phosphamide
ANEMIA CAUSED BY BLOOD
LOSS
 Acute blood loss

 Chronic blood loss

ACUTE BLOOD LOSS
ETIOLOGY
 Trauma

 Complications of surgery

 Conditions or diseases that disrupt vascular

integrity.
CLINICAL MANIFESTATIONS
Volume lost 10 %
None

Volume lost20%
No detectable signs or symptoms at rest,
tachycardia with exercise and slight
postural hypotension

Volume lost30%
Normal supine blood pressure and pulse rate at
rest ,postural hypotension and tachycardia with
exercise.
CLINICAL MANIFESTATIONS
Volume lost 40%
Blood pressure,central venous pressure,and
cardiac output below normal at rest,
rapid,thread pulse and cold clamy skin.

Volume lost 50%

Shock and potential death
CLINICAL MANIFESTATIONS
 Alert to patients expression of pain

 Internal hemorrhage cause pain

 Retro peritoneal bleed- may not experience

abdominal pain
MANAGEMENT
 IV fluids - dextran, hetastarch, albumin, and/or
crystalloid electrolyte solutions such as lactated
Ringer's.

 Blood transfusions (packed RBCs) may be needed if

the blood loss is significant.

 If the bleeding is related to a platelet or clotting

disorder, replacement of that deficiency is
addressed.

 supplemental iron
CHRONIC BLOOD LOSS
 Bleeding ulcer

 Hemorrhoids

 menstrual and postmenopausal blood loss

etc.
HEMOLYTIC ANEMIA
 Condition caused by destruction or hemolyis
of RBCs at a rate that exceeds production.

 Occur because of problems intrinsic or

extrinsic to the RBC
ETIOLOGY
 Intrinsic hemolytic anemia( heriditary)

*Abnormal hemoglobin
Sickle cell anemia
Thalassemia

*Red blood cell membrane abnormality

Heriditory spherocytosis

*Enzyme deficiencies
G6 PD deficiency
ETIOLOGY…
 Extrinsic hemolytic anemia( Acquired)

* damage is caused by external factors

such as trapping of cells within the sinuses of
the liver or spleen

* Antibody mediated destruction(Auto

immune hemolytic anemia)
CLINICAL MANIFESTATIONS
 General symptoms of anemia

 Jaundice

 Enlarged liver and spleen

MANAGEMENT

 Focus of treatment is to maintain renal

function
SICKLE CELL DISEASE
 Group of inherited, autosomal
recessive disorders characterized
by the presence of an abnormal
form of Hb in the erythrocyte.

 This abnormal Hb, hemoglobin S (Hb S),

causes the erythrocyte to stiffen and
elongate taking on a sickle shape in response
to low oxygen levels.
ETIOLOGY
 Sickle cell anemia

 Sickle cell thalassemia

 Sickle cell Hb C disease

 Sickle cell trait

SICKLE CELL ANEMIA

 Occurs when is homozygous for hemoglobin

S; the person has inherited Hb S from both
parents
SICKLE CELL THALASSEMIA AND
SICKLE CELL HB C

 Occurs when a person inherits Hb S from one

parent and another type of abnormal
hemoglobin( thalassemia or Hb C) from other
parent
SICKLE CELL TRAIT

 Occurs when a person is heterozygous for Hb

S; the person inherits hemoglobin S from one
parent and normal hemoglobin(Hb A) from
another parent
SICKLING EPISODES
 Triggered by low oxygen tension in the blood
 Hypoxia can be caused by

* viral or bacterial infection

* high altitude
* emotional or physical stress
* blood loss
SICKLING EPISODES…
Sickled RBC become rigid and take an
elongated cresent shape

Cannot easily pass through capillaries

Cause vascular occlusion

Acute or chronic tissue injury

SICKLE CELL CRISIS
Blood flow is impaired by sickled cells

Vasospasm occurs

Severe capillary hypoxia

Changes in membrane permeability

Plasma loss
Hemo-concentration and development of thrombi

Further circulatory stagnation

SICKLE CELL CRISIS…
 Tissue ischemia, infarction and necrosis
occurs from lack of oxygen

 Shock can occur (life threatening consequence)

CLINICAL MANIFESTATIONS
 Features of anemia( pallor of mucous
membranes, decreased exercise tolerance)
 Jaundice
 Primary symptom associated with sickling is
pain
- pain is severe
- affect an area of the body with the
back, chest, extremities and abdomen being
mostly affected
CLINICAL MANIFESTATIONS….
 Damaged vision: The sickled blood
cells, often clog the blood vessels that
connect to the retina, causing optical
damage.

 Limited Growth: The scarcity of

oxygen caused by sickle-cell anemia is
detrimental to healthy human growth.
DIAGNOSTIC MEASURES
 Peripheral blood smear
 Sickling test
 Electrophoresis of hemoglobin
 Jaundice
 Skeletal X- rays
 MRI scan
 Doppler studies
COMPLICATIONS
 Infections
 Pulmonary complications
Pneumonia
Acute chest syndrome
Pulmonary hypertension
 Cardiac complications

MI
HF
corpulmonale.
COMPLICATIONS…..
 Ophthalmic complications
Retinal vessel obstruction may result
in
Hemorrhage
Scarring
retinal detachment
blindness.
 Renal complications

Renal failure.
 Neurologic complications

Stroke
COMPLICATIONS…..
 Musculoskeletal complications
Osteoporosis
Osteosclerosis
 Integumentory system complications

Chronic leg ulcers

 Genitourinary system complications

Priapism
MANAGEMENT
 No specific treatment for the disease

 Focus on alleviating the symptoms and

minimizing end organ damage

 Instruct to avoid high altitude, maintain

adequate fluid intake and treat infections
promptly

 Chronic leg ulcers treated with bed rest,

antibiotics, warm saline soak, mechanical
debridement and grafting
SICKLE CELL CRISIS
MANAGEMENT
 Oxygen administration

 Fluid administration

 Transfusion therapy

 Pain management

 Acute chest syndrome treated with broad spectrum

antibiotics, oxygen therapy and fluid therapy

 Antisickling agents(Hydroxy urea)

MANAGEMENT….
 Hematopoietic stem cell transplantation

* Allogenic
* Syngenic
* Autologous