ANEMIA

Dr. Odi Khasawneh

Done by:
Melad Dababneh & Hothaifah Abo-Romman
 What is Anemia?
• Decrease the level of Hb in the blood below the
reference range for the age, sex and race of the
individual.

• Normal results for adults vary, but in general are:

Male: 13.8 to 17.2 (g/dL)
Female: 12.1 to 15.1 g/dL

• Normal results for children vary, but in general are:

Newborn: 14 to 24 g/dL
Infant: 9.5 to 13 g/dL
 WHO's Hemoglobin thresholds
Age or gender Hb threshold Hb threshold
group (g/dl) (mmol/l)
Children (0.5–5.0 11.0 6.8
yrs)
Children (5–12 11.5 7.1
yrs)
Teens (12–15 12.0 7.4
yrs)
Women, non- 12.0 7.4
pregnant
(>15yrs)

Women, pregnant 11.0 6.8

Men (>15yrs) 13.0 8.1

 Epidemiology
• It is the most common disorder of the blood
• 30% of world population have anemia
• Half of these are iron deficiency anemia

• Anemia is common in menstruating women,

children and elderly patients
• 20% of children in the United States and 80%
of children in developing countries will be
anemic at some point by the age of 18
 Clinical Presentation
• Anemia goes undetermined in many people, and symptoms can be minor
or vague
• The signs and symptoms can be related to the anemia itself, or the
underlying cause

• Asymptomatic
(non-specific)

• Feeling of weakness
• Fatigue
• Dizziness
• Headache
• Dyspnea
• Palpitation (the body may compensate for the lack of oxygen carrying
capability of the blood by increasing cardiac output)
• Angina
• Intermittent claudication
• Parasthesia in fingers and toes
 Approach to Anemia
• History
• Physical examinations
• Investigations
 Hx
• Symptoms of Anemia

• History of bleeding, hematemesis or melena.

• History of renal disease, liver disease, thyroid disease,

rhematological disease, chronic infections or recent illnesses.
• Family history of anemia, blood diseases or chronic illnesses.
(SCA, Thalessemia, …)

• Nutritional history and socioeconomic status:

- Dietary habits
▫ Inadequate Iron or protein intake: Iron Deficiency
▫ Strict Vegetarian: Vitamin B12 Deficiency
▫ Diet lacking fruits and vegetables: Folate Deficiency
▫ Hx of Fava beans ingestion? G6PD
Hx
• History of Gastrectomy or Malabsorption
(e.g. Diarrhea)

• Medications or Substance abuse:

- Aspirin, NSAIDs  GI bleeding
-Anticonvulsants, methotrexate, alcohol  Folate def.
-Oxidant (antimalarial)

• Other related symptoms accordingly.

? Abdominal pain
PE
General Look + Vital Signs?

The general signs exhibited may include:

• Pallor:
Pale Conjunctiva or mucous membranes
• Pallor at the nail beds or palmar creases

• Dyspnea

In severe anemia, there may be signs of a hyperdynamic

circulation:
• Tachycardia
• Cardiac enlargement
• Systolic ejection murmur
PE
• Face:
PE
• Face:
PE
• Face:
PE
• Hands
PE
• Skin  Pallor , jaundice , pigmentation , bruises &
petechia
• Chest  Cardiovascular examination: S1 , S2 , Ejection
systolic murmurs
• Abdomen: Liver & Spleen

• Signs of underlying causes

- Hypothyroidism - RA
• Lower limb  Edema, Ulcers,..

• Neurological examination

• Full lymph node examination

• There may be signs of specific causes of anemia:

• Jaundice (in hemolytic anemia)

• Bone deformities - Skull (found in thalassaemia major)
• Leg ulcers (seen in sickle cell disease)
• Koilonychia, chielosis and brittle nails (IDA)
• Neurologic findings – abnormal reflexes, babinski,
ataxia, poor position & vibration sense. (B12 deficiency)
• Organomegally (Splenomegaly  hemolysis, leukemia,..)
• Pica?
Investigation and Diagnosis
• Done by lab tests :
• CBC (request in the first batch of blood tests in the
diagnosis of an anemia)
1.number of red blood cells
2.hemoglobin level
3.Hemoglobin concentration
4.Reticulocyte count.

• RBC Indices :
1.MCV 2.MCH 3.MCHC 4.RDW
• Blood Film

• Bone marrow

• And other tests.

Classification of the anemia:
• Excessive blood loss.

• Excessive blood cell destruction (hemolysis)

 Hereditary spherocytosis
 Sickle cell anemia
 Prosthetic valve

• Deficient red blood cell production (ineffective

hematopoiesis).
 Iron deficiency anemia (deficient heme synthesis)
 Thalassemias (deficient globin synthesis)
Microcytic anemia
 1-Iron Deficiency Anemia
• It is the most common cause of anemia world
wide.
• Most common cause of affecting women in
childbearing age “menses”
• Most common cause of anemia affecting
children “nutritrional anemia”
• The diagnosis of iron deficiency anemia will be
suggested by appropriate history
 Physiology
• Normally circulating RBC life span is 120 days
• Fe is primarily supplied by destruction of old
RBC
• Fe absorption is about 10% of the intake and
change according to the body need
• Fe is mainly absorbed in the deodenum in the
ferrous state and is enhanced by the presence of
gastric juice, amino acid and Vit C
 IDA begin as normocytic
and the microcytic follows
Hb drop of 2g/dl

Daily need of iron 1-2mg

Pregnant 3mg
Lactating women 4mg
 Causes of IDA
• Blood loss: menorrhagia, GIT bleeding (PU,
malignancies, diverticulitis, hookworm,
schistosomiasis and NSAIDs)
• Malabsorption: hypochlorhydria, gastric
surgery, celiac disease
• Physiological demand: infancy, puberty and
pregnancy.
• Poor intake: mainly in childhood (nutritional
anemia).
Clinical features:
Symptoms of anemia.. Dysphagia?
Signs: atrophic glossitis, angular stomatitis, koilonychia,

Investigations:
CBC: decrease Hb and hematocrit, increase platelet
RBC INDICES:
* MCV decreased (Normal 80-100)
* MCH decreased (Normal 27-32)
* MCHC increased

BLOOD FILM:
* Microcytic hypochromic RBC
* Poikilocytosis (abnormally shaped RBC’s )
* Anisocytosis (RBC’s of unequal size)
 Ferritin level: low (if normal do I exclude IDA??)

TIBC: high

Transferrin saturation <16%

Serum soluble transferrin receptor is high.

Investigate for the cause: in men and postmenauposal women:

R/O GIT cause.
 Treatment
• Treat the underlying cause if present.
• Oral ferrous sulphate (325mg twice daily) for 3-6
months to replete iron stores (increase of retic. count
followed by increase Hb - 1g/dl every week after the third
week)
• S/E:
▫ Nausea
▫ Metallic taste
▫ Heartburn
▫ Constipation
▫ Black stool
• Parenteral iron only if pt is intolerant to oral therapy
(ongoing blood loss, IBD, severe iron deficiency,
malabsorption)
• Blood transfusion
• Failure of tt of iron are due to:
1. Non compliance
2. Ongoing blood loss
3. Malabsorption
4. Wrong dx
 2-Thalassemia
• Is an inherited autosomal recessive blood disease
• Thalassemia has higher incidence in the Mediterranean
region (Arabs and Asians).
• The Maldives has the highest incidence of Thalassemia in
the world with a carrier rate of 18% of the population.
• Thalassemia is a quantitative problem (unlike sickle-cell
anemia which is a qualitative problem).

• The two major forms of the disease:

* Alpha thalassemia: prevalent in peoples of Western
African descent.
* Beta thalassemia: particularly prevalent among
Mediterranean people.
 Pathopysiology
• Normal hemoglobin is composed of two α chains
and 2 β chains.
• Thalassemia is classified according to which
chain of the hemoglobin molecule is affected.
• In alpha thalassemia the production of the α
globin chain is affected.
• In beta thalassemia the production of the β
globin chain is affected.
 A)Alpha (α) thalassemia
• It is autosomal recessive involving the genes
HBA1 and HBA2. It is also connected to the
deletion of the 16p chromosome.
 4 globin chains 
if 1α chain deleted  no clinical effect (silent carrier)
if 2α chains deleted  mild hypochromic anemia
(α thalassemia minor)
if 3α chains deleted  Hb H disease
if 4α chains deleted  incompatible for life  hydrops fetalis
 The excess β chains form unstable tetramers called Hemoglobin H (Hb H)
composed of 4 beta chains which have abnormal oxygen dissociation
curves.
 Hb H is functionally useless, so that patients rely on their low levels of Hb
A for oxygen transport.
 Treatment of Hb H disease is similar to that of beta thalassemia
intermediete severity, involving folic acid supplement, transfusion if
required and avoidance of iron therapy.
 B)Beta (β) thalassemias
• It is autosomal recessive. Occur due to mutations in the
HB B gene on chromosome 11
• Ineffective erythropoiesis is the main cause of anemia.
• The severity of the disease depends on the nature of the
mutation

• Decrease production of ß chains excess α chains

combined with δ or γ chains  Hb A² or Hb F
 Classification of ß Thalassemia
 ß thalassemia minor
one allele is affected (β+/β or βo/β)
Asymptomatic heterozygous carrier state (trait).
Mild anemia with low MCV and MCH
Fe store and ferritin level is normal
High HbA2 (>3.5%)
ß thalassemia intermedia

Medium condition between minor and major

(β+/β+or βo/β)
Moderate anemia (7 -10)
Doesn’t require blood transfusion
Ex: HbC thalassemia.
ß thalassemia major
Both alleles have mutations (β+/βo or βo/βo or
β+/β+)
Homozygous thalasssemia
Present in the fist year of life as severe anemia,
FTT, recurrent infection
Hypertrophy of ineffective BM
Maxillary and frontal prominence
Hepatosplenomegaly due to extramedullary
hematopoiesis.
High level of Hb F
 Investigations
• CBC
Microcytic hypochromic anemia
Increase reticulocyte
• BLOOD FILM
Target cells
Anisocytosis
Nucleated RBC in peripheral blood
• HB electrophoresis
High Hb F
Decrease Hb A
some have high HBA2.
 TREATMENT
• Patients with thalassemia minor usually do not require any specific
treatment.

• Patients with thalassemia intermedia can often manage a normal

life but may need occasional transfusions like at times of illness or
pregnancy, depending on the severity of their anemia.

• Treatment for patients with thalassemia major includes:

* blood transfusion to keep Hb >10g/dl
* iron chelation due to iron overload
* Splenectomy
* allogeneic hematopoietic transplantation (BM transplant)
 Iron Chelation
• Iron overload can damage the endocrine gland, liver, pancreas and
give heart toxicity

• Deferoxamine: is the intravenously or subcutaneously

administered chelation.

• Deferasirox: is an oral iron chelation drug.

• Indicaxanthin:
* found in beets
* powerful antioxidant which is more effective than either Trolox or
Vitamin C.
 Prevention
• Genetic counseling and screening for couples
and decrease consanguinity marriage.
• Antenatal Dx using fetal blood and DNA
analysis.
Macrocytic anemia
 1-Megaloblastic anemia:
• Is an anemia that results from inhibition of DNA
synthesis in red blood cell production.

• This will cause in an arrest of nuclear maturation ,

with normal cytoplasmic development resulting in
MEGALOBLASTIC ANEMIA
• This is often due to deficiency of vitamin B12 and/or folic
acid.

• It is characterized by:

- many large immature and dysfunctional red blood cells

(megaloblasts) in the bone marrow

- and also by hypersegmented neutrophils.

megaloblasts in the bone marrow Hypersegmented neutrophils
A) Vitamin B12 deficiency
• Average daily diet contains 5-30 microgram,
reqiurement is about 1 microgram.
• Found in Egg, meat, fish and milk
• Body store of B12 last for years.
• Liver stores enough B12 for 3 years
• Gastric acid release B12 from food
• Intrinsic factor (IF) is essential for B12 absorption.
• Binding of IF require high pH (pH 8)
• B12-IF complex is absorbed in the terminal ileum.
 VIT B12 ABSORPTION
• Vit B12 is released from food by gastric
enzymes  at gastric pH, it binds to R protein (a
carrier protein)  as gastric emptying occur,
pancreatic secretion rises the pH  vit B12
switches place from the R protein to IF released
from parietal cell (in the gastric)  vit B12-IF
complex is absorbed in the terminal ileum  Vit
B12 is transported by enterocytes to the plasma
where it binds to transcobalamin II  carried by
transcobalamin II to the tissues for utilisation
 Causes:
 Dietary Factors: Vegans.

 Gastric Factors: Hypochlorhydria, gastric surgery

(gastrectomy ? IDA).

 Pernicious anemia: autoimmune disease that affects the

parietal cells
- Pernicious anemia vs ileal cause  do Schilling test.
(ptn with B12 deficiency but –ve anti-IF should do Schilling
test to determine whether there is B12 malabsorption, and if
so, where it is occurring)

 Small bowel factors: resection of the terminal ileum ,

pancreatic insufficiency , crohn’s disease, celiac disease or
tropical sprue, bacterial overgrowth (scleroderma, celiac
disease, chronic pancreatitis, Ig A deficiency, etc.)
• Schilling test
 SYMPTOMS

• Malaise (90%) • Poor memory

• Breathlessness (50%) • Depression
• Parasthesia (80%)* • Hallucination
• • Visual disturbances (due to
Sore mouth (20%)
optic nerve atrophy)
• Weight loss
• Paraplegia, ataxia and
• Altered skin pigmentation weakness (subacute combined
• Grey hair degenerative of spinal cord)
• Impotence
 SIGNS

• Smooth tongue
• Angular cheilosis
• Vitiligo
• Skin pigmentation
• Heart failure
• Pyrexia
Investigations:
• CBC, RBC indices and blood film  macrocytic anemia, MCV >110 and
hypersegmented neutrophil nuclei
• Serum B12 is low <50ng/L (norm. >160ng/L)
• Serum autoAb
• Serum ferritin elevated
• BM examination (not necessary)  hypercellularity with megaloblastic
changes

Management:
• Adminster: IM hydroxycobalamine 
- 1 microgram in 5 divided doses for every other day for 10 days
- 5 divided doses for every week for 5 weeks
- 1/month for at least 1 year
B) Folate Deficiency Anemia
Another cause for megaloblastic anemia.
Folate is found in green vegetables, fruits and
animal proteins (liver and kidney).
 Absorbed in the Jejunum
Daily requirements  100-200μg and body
stores are sufficient for 3-4 months.
Causes of folate deficiency:
 Dietary factors: poor vegetables intake , alcohol
excess, anorexia
 Malabsorption: Celiac disease, Crohn’s disease
 Excess utilization:
# pathological  chr. hemolytic anemia
# physiological  pregnancy, lactation

 Drugs: phenytoin, trimethoprim, sulfasalazine,

methotrexate.
• Clinical features: similar of B12 def. but without neurological features.
• Investigations:
• CBC, RBC indices and blood film
• Low Red cell folate -more accurate guide to tissue folate than serum
folate.( norm 160-640μg/ mL.)
• Investigate for the cause
• Treatment:
* Oral folate 5mg daily for 3 weeks and then 5mg weekly as
maintenance.
* Prophylactic folate is given to patient with chronic hemolysis
(autoimmune hemolytic anemia or hemoglobinopathies) and pregnancy.
• Note:
If the pt was very ill, don’t wait the result of B12 and
folate levels and treat with both. If you use folate alone you
may exacerbate the neurological defects in vit. B12 deficiency.
 2-Non Megaloblastic anemia:
• Physiological cause:
i. Pregnancy

• Pathological cause:
i. Chronic liver disease
ii. Alcohol
iii. Hypothyroidism (Macrocytosis is found in up
to 55% patients with hypothyroidism and may
result from the insufficiency of the thyroid
hormones themselves)
Normocytic anemia
 1. Sickle-cell disease
• Is an autosomal recessive genetic blood
disorder
• Characterized by red blood cells that assume an
abnormal, rigid, sickle shape
• Life expectancy of RBCs is shortened
• Sickle-cell disease, usually presenting in
childhood
• With studies in 1994, in the US, reporting an
average life expectancy of 42 in males and 48 in
females ( Nowadays ? >50)
 Precipitating factors for
crisis:
-hypoxia.
-acidosis.
-dehydration.
-infection

.
 Pathophysiology
• Sickle-cell anaemia is caused by a point mutation in the
β-globin chain of haemoglobin
• Glutamic acid is been replaced by valine at the sixth
position
• The β-globin gene is found on the short arm of
chromosome 11
• The loss of red blood cell elasticity is central to the
pathophysiology of sickle-cell disease
• The actual anemia of the illness is caused by hemolysis
• Sickle cells only survive 10–20 days, Healthy red blood
cells typically live 90–120 days
Sickle cell crisis:
# Vaso-occlusive crisis: (painful crisis )
Sickle-shaped red blood cells obstruct capillaries and
restrict blood flow to an organ resulting in ischemia, pain,
necrosis and often organ damage
# Splenic sequestration crisis:
Is a common complication of sickle cell anemia in children.
results when intrasplenic sickling prevents blood from leaving
the spleen and acute painful splenic engorgement occur.
Abdomen will become bloated and very hard (emergency)
# Aplastic crisis: triggered by infection of parvovirus B19.
# Haemolytic crisis. Common in patient with co-exist with
G6PD deficiency
# Acute chest syndrome. Triggered by painful crisis, resp.
infxn, BM embolisation, atelactesis and surgery
Complications
• Stroke
• Cholelithiasis and cholecystitis
• Osteomyelitis (SALMONELLA)
• Leg ulcer
• Chronic renal failure
• Pulmonary hypertension

Diagnosis
• full blood count:
-reveals haemoglobin levels in the range of 6–8 g/dL with a high reticulocyte count
• blood film:
-show sickle cell and features of hyposplenism (target cells and Howell-Jolly bodies)
• haemoglobin electrophoresis:
-Abnormal haemoglobin forms of HbS can be detected
Management
• Folic acid and penicillin V:
-These patients will take a 1 mg dose of folic acid daily for life. From
birth to 5 years of age, they will also have to take penicillin V to
protect against pneumococcal infection.

• Painful (vaso-occlusive) crisis: (treat aggresively)

-rehydration
-O2 therapy
-Analgesia (NSAIDs or Opioid)

• Acute chest crisis:

-Management is similar to vaso-occlusive crisis, with the addition
of antibiotics (quinolone or macrolide)
 2. G6PD deficiency
 Most common inherited red cell enzymopathy
 up to 10% of those with African and Mediterranean descent

 Inheritance is X-linked.

 Neonatal jaundice occur, but most are symptomless with

normal Hb and blood film.

 They are susceptible to oxidative crises precipitated by

drugs (e.g. , sulfonamide), exposure to the bean (favism)
or illness.

 Typically there are rapid anemia and jaundice.

Clinical manifestations:
Children usually present clinically with:
# Neonatal jaundice (world wide it is the most cause
of severe neonatal jaundice requiring exchange
transfusion)
# acute hemolysis-precipitated by:
*infection
*certain drugs
*fava beans
*naphthalene in mothballs
# Intravascular hemolysis is associated with fever,
malaise and the passage of dark urine as it contains
hemoglobin as well as urobilinogen.
# The hemoglobin levels falls rapidly.
Diagnosis:
*Between episodes, almost all patients have a completely
normal blood picture.
*The diagnosis is made by measuring G6PD activity in RBC.
*During a hemolytic crisis, G6PD may be misleading elevated
due to the higher enzyme concentration in reticulocytes.
*A repeat assay then required in the steady state to confirm the
diagnosis.

Laboratory diagnosis:
▫ Bite cells
▫ Heinz bodies

Management:
▫ Supportive (blood transfusion)
▫ Avoid precipitants
▫ Counsel patient/family
*The parents should be given advice about the sign of acute
crisis and provided with a list of drugs, chemicals and food to
avoid.
Evaluation of hemolysis:
Peripheral blood smear:
• Serum unconjugated bilirubin..Increased
• Serum LDH.......Increased
• Serum haptoglobin.....Decreased
• Reticulocyte count....Increased
Urine analysis:
• Urine hemoglobin...Present
• Urine hemosiderin...Present
• Urine urobilinogen...Increased
 3- Anemia of chronic diseases:
• Chronic renal failure:
# Decreased erythropoietin
# Anemia of chronic illnesses
# Uremia cause stress ulcer and suppress the bone
marrow

• Thyroid disease:
# Loss of iron by Menorrhagia (microcytic anemia)
# Pernicious anemia (Pernicious anemia occurs 20
times more frequently in patients with hypothyroidism
than generally- Macrocytic anemia)

• Collagen Vascular disease

• Rheumatoid Arthritis:
1. Iron utilization is impaired
2. Reduced erythropoietin levels
3. Decreased bone marrow response to erythropoietin.
4. Premature destruction of red blood cells
5. Drug associated anemia : Bone marrow suppression from
drug therapy i.e. gold / penicillamine / Methotrexate.
6. Intercurrent infection

• SLE
• Polymyositis
• Polyarteritis
• Inflammatory bowel disease ( UC , CD )
Thank You