2. Anemia
� Is a decrease in number of red blood cells (RBC) or less than normal
quantity of hemoglobin in the blood.
� The normal range varies with age, so anemia can be defined as:
3. Etiologies
� PRODUCTION DEFECTS:
• Nutritional deficiencies- vitamin B12, folate or iron deficiency
• Inflammation/ chronic diseases
• Bone marrow disorder- pure red cell aplasia, myelodysplasia
� BLOOD LOSS
• Hemorrhage
• Chronic GI bleeding
� BLOOD DESTRUCTION
• Hemolysis
• Sequestration (hypersplenism) – usually associated with mild pancytopenia
4. ASSESSMENT
� Diagnosed is made by :
• Patient history
• Physical examination
• Haematological lab findings
� Identification of the cause of anemia is important so that appropriate
therapy is used to treat the anemia
5. PATIENT HISTORY
� Dietary habits
� Medication
� Possible exposure to chemical / toxins
� Description and duration of symptoms
� Failure to thrive
� Tiredness
� Headache and vertigo
� Dyspnea from exertion
� GI problems
� Overt signs of blood loss such as hematuria or black stool
6. �PATIENT WITH ACUTE AND SEVERE
ANEMIA APPEAR IN DISTRESS WITH
TACHYCARDIA , TACHYPNEA,
HYPOVOLEMIA
�PATIENT WITH CHRONIC ANEMIA
TYPICALLY WELL, COMPENSATED
AND USUALLY ASYMPTOMATIC
7. HEMATOLOGICAL LAB FINDINGS
� Hematocrit ( HCT) or pack cell volume in %
� Hemoglobin ( Hgb) concentration
� RBC count
� Reticulocytes
� Mean corpuscular volume ( MCV) –HCT / RBC x 10
� Mean corpuscular hemoglobin ( MCH) – average weight of hemoglobin /
cell in picograms
• Varies according to age
8.
9. � Red cell distribution width(RDW)-measurement variation size of RBC
• Normal range 11.5-14.5%
• >14.5 means increased variation size above normal amount
• <11.5 means RBC population more uniform than normal
� Low RDW
• There is no haematologic disorders associated with a low RDW results
� Normal RDW and normal MCV.
• People with normal results may still have anemia caused by a chronic medical condition or blood
loss.
� Normal RDW and low MCV.
• This combination may indicate anemia caused by a chronic condition or thalassemia.
� Normal RDW and high MCV.
• This can indicate a liver condition or alcohol abuse. Or, a person may have this result because they
are on antiviral drugs or chemotherapy. If other blood characteristics are also affected, this can
suggest aplastic anemia, a rare disorder caused by inadequate blood cell production.
� High RDW count- if results are above the normal range, this is known as a high RDW count.
• It can indicate:Macrocytic anemia. This is characterized by red blood cells that are larger than
average. Macrocytic anemia is linked to a deficiency of folate or vitamin B-12.Microcytic anemia.
This involves red blood cells that are smaller than average. It is usually caused by a deficiency of iron,
but it may also suggest thalassemia.
10. CLASSIFICATION OF ANEMIA
MORPHOLOGICALLY
� Microcytic � Normocytic � Macrocytic
• Iron deficiency anemia
• Thalassemia
• Sideroblastic anemia
• Chronicle infection
• Severe malnutrition
• Acute blood loss
• Infection
• Renal failure
• Liver disease
• Early iron deficiency
• Normal newborn
• Increased erythropoiesis
• Post-splenectomy
• Liver disease
• Obstructive jaundice
• Hypothyroidism
11.
12. MANAGEMENT
� Acute anemia usually warrants immediate medical attention
� Treatment depends on the severity and underlying cause of the anemia
� Supportive measures such as supplemental oxygen for decreased oxygen
carrying capacity,fluid resuscitation for hypovolemia, or activity restriction
for fatigue
13. IRON DEFICIENCY ANEMIA
� Diagnosis :
• Low MCV, low MCH
• Smear : microcytic & hypochromic
• Additional diagnostic test:
✔ Serum ferritin - decreased
✔ Serum iron – decreased
✔ Iron binding capacity – increased
✔ Iron saturation – decreased
✔ Mentzer Index – MCV/RBC
o A Mentzer index <13 suggests that patient has thalassemia trait
o Index >13 suggests that the patient has iron deficiency
14. Treatment
� Nutritional counselling : if breast fed, maintain breastfeeding. Also can use
iron fortified cereals
� Oral iron supplementation :
• 6mg/kg/day of cereal elemental iron
• Continue for 6-8weeks after Hb level restored to normal
� Syrup FAC (ferrous ammonium citrate) – 86mg/5ml
� T. Ferrous fumarate 200mg has 65mg elemental iron per tablet
15. DOSE CALCULATION OF SYRUP FAC
(6mg/kg)
� Every 5ml has 86mg elemental iron
So, in 0.06ml has 1mg elemental iron
If child weighs 10kg,
= (weight x 6) x 0.06
= 3.5ml
16. B12/ FOLATE DEFICIENCY
� Smear : macrocytic RBC (high MCV)
� B12
• Low serum B12
• Anti-IF Abs
� Folate
• Serum level can be normalized with a single meal
Treatment
� B12 deficiency: IM B12 1mg/month , PO B12 1-2mg/ day
� Folate deficiency : improve diet, folate 1mg/day
17. HEREDITARY SPHEROCYTOSIS
� Due to inheritance of defective structural protein(spectrin ) in RBC membrane
producing spheroidal and osmotically fragile RBCs
� Degree of clinical severity proportional to the severity of RBC membrane defect
� Inheritance : AD in 2/3 , AR or de novo in 1/3
Clinical Features
• Anemia
• Intermittent jaundice
• Splenomegally
• Pigment gallstones in adolescent and young adult
• Aplastic crises with parvovirus B19 infection
• Megaloblastic crises(all patients need to receive folate supplement)
18. Rare manifestation
• Leg ulcer
• Spinocerebellar ataxia
• Myopathy
• Extramedullary hematopoetic tumours
Investigations
• Reticulocytosis
• FBP : microspherocytes seen
• Osmotic fragility increased
• MCHC increased
• Normal DAT
• Autohemolysis increased and corrected by glucose
19. Treatment
• Folic acid supplements
• Splenectomy – to be delayed as long as possible; in mild cases, avoid
splenectomy unless gallstones developed.
• Splenectomy is avoided for patients <5 years age because of the
increased risk of post-splenectomy sepsis due to capsulated bacteria . For
patient planned for splenectomy , give pneumococcal, Hemphillus,
meningococcal vaccination 4-6 weeks prior to splenectomy and
prophylactic oral penicillin given post-splenectomy for life.
20. GLUCOSE 6 PHOSPHATE
DEHYDROGENASE (G6PD) DEFICIENCY
• Definition : a common enzymopathy, X-linked
reduction in the activity of glucose-6-phosphate
dehydrogenase (G6PD), which makes erythrocytes
susceptible to oxidative stress and usually causes
acute hemolytic anemia in response to a “trigger.”
• 2 variants : African & Mediterranean
22. Favism
•Severe form of G6PD deficiency
•Haemolysis after ingestion or inhalation of materials released from fava beans
•Asians and Mediterranean but not in African Americans type
•Acute life threatening haemolysis within 24 hours of exposure
� Can cause severe haemolysis –jaundice – kernicterus
24. Investigation
Screening test
• A) Fluorescent spot test of Beutler using
• UV-light.
• Simplest & sensitive screening test. Based on the fluorescence of
NADPH if glucose-6-phosphate present in the tested RBCs.
25. Peripheral blood examination
• Bite cell & blister cells (due to Hb. retraction
from the membrane) with small contracted cells ---
-> polychromasia (Different coloration of RBCs).
• Denatured Hb. (Heinz bodies) will precipitate in
the RBCs and only seen by supravital staining.
Enzyme assay Method
• In most patient, the enzyme activity is < 20%.
DNA analysis: to study the
type of gene mutation.
26. MANAGEMENT
� Most cases do not need treatment
� however they must be taught to avoid the causes ie broad beans,drugs
and chemical which can cause oxidant stress
� Anemia should be treated with appropriate measures, recognizing that
hemolysis is self-limited and often resolves in 8 to 14 days
� for jaundice, phototherapy is given appropriately and if indicated,
exchange transfusion may be suggested
27.
28. SICKLE CELL ANEMIA
Sickle cell disease is a group of inherited red blood cell disorders that
affects hemoglobin,crescent or “sickle” shaped do not bend and move
easily and can block blood flow to the rest of the body
29. Clinical Feature
Acute onset of anaemia can result in a poorly compensated state
● Excessive sleeping (especially in infants)
● Fatigue
● Irritability
● Poor feeding
● Poor exercise tolerance
● Headache
● An elevated heart rate
● A systolic flow murmur
● Syncope
● Glossitis
● angular stomatitis
● spoon-shaped nail
● frontal bossing
30. Vaso-occlusive crises are often precipitated by the following
● Cold weather (due to vasospasm)
● Hypoxia (eg, flying in unpressurized aircraft)
● Infection
● Dehydration (especially from exertion or during warm weather)
● Acidosis
● Alcohol intoxication
● Emotional stress
● Pregnancy
31. INVESTIGATION
1. Peripheral blood
• Haemoglobin between 60 – 90 g/L
• Normochromic normocytic anaemia & “microcytic”
• Irreversibly sickled cell (ISC) indicates severity of hemolysis
• Increased indirect bilirubin, reticulocytosis & circulating nucleated red blood cells (erythroblast)
2. Haemoglobin electrophoresis
• Cellulose acetate estrase (CAE) electrophoretic
▪ When haemoglobin placed in an electrical field, it migrates toward the anode (+) depending on its
charge
▪ Haemoglobin variants carry different charge from normal Hb
▪ Hb S migrates more slowly than Hb A toward the anode (+)
▪ All Hb. electrophoresis should be done BEFORE blood transfusion (transfused RBCs disturb the
electrophoresis pattern)
• In sickle cell anaemia (homozygous (SS)): Hb-S mainly with few amount of Hb-F + NO Hb-A.
32. 3. Sickling test
• Patients blood is incubated with a strong reducing agent
(dithionite tube test (DTT) or Na-Metabisulphite)
• A drop of the mixture is putted on a slide and covered by cover
slide with the margins sealed by paraffin or petroleum jell
• In sickle cell anaemia (homozygous) sickling will occurs within few
minute, and in sickle cell trait (heterozygous), sickling is delayed &
unclear.
4. Hemoglobin solubility test
• Patient hemolysate (product resulting from the lysis of red blood
cell) is mixed with a reducing agent in a tube
• In sickle cell diseases, the Hb. is insoluble and show turbid cloudy
solution (The line on the reading rack are invisible)
• Hb-A is soluble and produce transparent solution
• This is a sensitive screening test for sickle cell disorders
33. MANAGEMENT
1. Prophylaxis
• Fully immunized against pneumococcal, Haemophilus influenzae type B and
meningococcus infection
o Increased susceptibility to infection, especially encapsulated organisms, e.g.
Streptococcus pneumoniae and Haemophilus influenzae type B because of functional
asplenia
• Daily oral penicillin throughout childhood
o To ensure full coverage of all pneumococcal subgroups
• Once-daily oral folic acid
o Increased demand for folic acid caused by the chronic haemolytic anaemia
2. Vaso-occlusive crises should be minimized by:
• Avoiding exposure to cold, dehydration, excessive exercise, undue stress, or hypoxia.
• This require practical measure 🡪 Dressing children warmly, giving drinks especially
before exercise, and taking extra care to keep children warm after swimming.
34. 3. Treatment of acute crises
• Painful crises: oral or intravenous analgesia according to need (may require opiates)
and good hydration (oral or intravenous as required)
• Infection: antibiotics
• Oxygen should be given if oxygen saturation is reduced
• Exchange transfusion is indicated for acute chest syndrome, stroke and priapism.
4. Treatment of chronic problems
• Children with recurrent hospital admissions for painful vaso-occlusive crises or acute
chest syndrome:
o Hydroxycarbamide
▪ Increases the HbF production and helps protect against further crises
▪ Requires monitoring for side-effects, especially white blood cell suppression.
o Bone marrow transplant
▪ For the most severely affected children (1–5%) who have had a stroke or who
do not respond to hydroxycarbamide
▪ Only possible if the child has an HLA-identical sibling who can donate their
bone marrow
▪ Cure rate is 90% but there is a 5% risk of fatal transplant-related complications.
36. Definition of
Thalassemia
• Thalassemias are heterogeneous group
of inherited disorders characterized by
the reduction or absence of synthesis
of either alpha or beta globin chains of
Hb.
• Here the globin chains are structurally
normal.
37. World:
Beta Thalassemia : 7-8%
More than -100 million carrier
� Malaysia: In Malaysia, the β-thalassaemia carrier rate
is estimated at 3-5%, most of whom are unaware of
their carrier / thalassaemia minor status.
� The carrier rates of α-thalassaemia and
Haemoglobin E (HbE) are 1.8-7.5% and 5-46%
respectively. HbE are found more in the northern
peninsular states.
Incidence
38. � Interaction between a β-thalassaemia carrier
with a HbE carrier may result in the birth of a
patient with HbE/β-thalassaemia or
thalassaemia intermedia with variable clinical
severity.
42. Mode of inheritance:
� Autosomal
recessive
� Heterozygote are
not affected.
� Homozygote or
compound
heterozygote (HbE
β thalassemia) are
affected.
43. Type of Thalassemia
▪ According to Hb synthesis:
Alpha thalassemia
Beta thalssemia
▪ According to degree of severity:
thalassemia major
thalassemia intermedia
thalassemia minor
▪ According to genetics:
Homozygous ,
Heterozygous
45. BETA
THALASSEMIA
� Usually and mostly they are caused by gene
mutations in the β gene in chromosome 11.
� A complete absence of β-globin chain
production -βº-thalassemia.
� A partial reduction β-globin gene production β+-
thalassemia.
47. β-Thal--Clinical
� β-Thalassemia Minor
� Minor point mutation
� Minimal anemia; no treatment indicated
� β-Thalassemia Intermedia
� Homozygous minor point mutation or more severe
heterozygote
� Can be a spectrum; most often do not require
chronic transfusions
� β-Thalassemia Major-Cooley’s Anemia
� Severe gene mutations
� Need careful observation and intensive treatment
48. Beta Thalassemia Major
❑Reduced or absent production of β-globin
▪ Poor oxygen-carrying capacity of RBCs Failure to
thrive, poor brain development
▪ Increased alpha globin production and
precipitation
�RBC precursors are destroyed within the marrow
❑Increased splenic destruction of dysfunctional RBCs
�Anemia, jaundice, splenomegaly
49. ❑Hyperplastic Bone Marrow
▪ Ineffective erythropoiesis—RBC precursors
destroyed
�Poor bone growth, frontal bossing, bone pain
▪ Increase in extramedullary erythropoiesis
❑Iron overload—increased absorption and
transfusions
Endocrine disorders, Cardiomyopathy, Liver failure
50. A. EXCESS ERYTHROPOIESIS:
� Facial changes-
Maxillary over growth,
malocclusion of teeth, frontal
bossing, chronic sinusitis,
impaired hearing.
51. •Bone changes:
� Medullary expansion -
cortical thinning, risk of
fracture, osteopenia,
osteoporosis, back ache.
� Vertebral expansion lead
to spinal cord
compression-neurological
manifestations.
Medullary expansion
54. B. IRON OVERLOAD:
1. Endocrine failure:
� Short stature.
� Delayed puberty.
� Estrogen/ Testosterone
deficiency.
� Hypothyroidism.
� Diabetes mellitus.
� Hypoparathyroidism.
β thalassemia major
Male 18 years
59. � Acute haemolytic reactions
� Delayed transfusion reaction
� Autoimmune haemolytic anaemia
� Febrile transfusion reaction
� Allergic reaction
� Transfusion-related acute lung injury (TRALI)
� Graft versus host disease (GVHD)
� Volume over load.
� Transfusion of disease – HAV,HBV, HIV
F. Complications due to Blood transfusion::
60. � Congestive heart failure.
� Cardiomyopathy.
� Sepsis due to increase susceptibility to
infection.
� Multiple organ failure due to
hemochromatosis.
CAUSES OF DEATH IN
THALASSEMIA
62. α Thalassemia
� Is usually caused by deletion of 1 or more of
the 4 α globin genes on chromosome 16.
� Severity of disease depends on number of
the deleted α genes.
� Absence of α chains will result in increase
excess of γ globin chains during fetal life
and excess β globin chains later in postnatal
life.
63. α Thalassemia
α2 α1 α2 α1
α2
α2 α1
α2 α1
α2 α1
α2 α1
α2 α1
α2 α1
Normal Hb
One α gene deletion
silent carrier
Two α gene deletions
α-Thal. Minor
Four α gene deletions
Hydrops fetalis or also
called:
Erythroblastosis Fetalis.
Three α gene deletions
Hb-H disease
64. Infants with severe α
Thalassemia (zero
functional alpha genes)
and Hb Barts suffer
from-
• severe intrauterine
hypoxia.
• born with massive
generalized fluid
accumulation,
Condition known as
hydropsfetalis or
erythroblastosis fetalis.
65. HbE Beta Thalassemia:
� Most common type of thalassemia seen in Bangladesh
and alsi in South-East Asia.
Clinically 3 types:
� Mild Hb E beta thalassemia.
� Moderately severe Hb E beta thalassemia – usualy
resemble thalassemia intermedia.
� Severe Hb E beta thalassemia- resemble thalassemia
major
74. • Widening of diploic space
• Hair on end appearance
• Thinning of cortex
X-ray skull
75. X-ray hand
- Rectangular appearance
- Widening of medullary cavity with coarse
trabecular pattern
- Thinning of cortex
76. Investigations
� Osmotic fragility : Decrease
� Liver biopsy : To measure liver iron
concentration (LIC)
� T2 MRI : To measure LIC & cardiac iron
• DNA analysis : Determine specific defect at
molecular DNA level
79. Treatment of alpha thalassemias:
� Patients with silent carrier & alpha thalassemia
trait do not require any treatment.
� HbH disease – usually does not require regular
transfusions. But, Hb levels may fall with
intercurrent illnesses & patients may require
transfusion at such times.
❖Patients with beta thalassemia minor usually do
not require any specific treatment.
80. ❑Hb E-Beta thalassemia-
� Mild- no treatment
� Moderate- normally requires no transfusion
unless infection precipitate anemia
� Severe- similar to major with regular transfusion
and chelation therapy.
81. Standard Transfusion Regimen for
Beta Thalassaemia Major
� Regular blood transfusions administered every 3-6
weekly ( interval varies depending on patients)
� The goal of transfusions is to maintain the pre-transfusion
Hb between 9-10 g/dl.
� Keep mean post-transfusion HB at 13.5- 15.5g/dl
� Keep mean Hb 12- 12.5g/dl
� Packed RBC=15- 20 ml/kg over 3- 4 hour
82. When to start blood transfusion?
� After completion of blood investigation for confirmation of diagnosis,
� - Hb <7g/dl on 2 occasions > 2 weeks apart ( in the absence of other
factor like infection)
- Hb >7 in beta thalassemia major/ severe forms of HB e Beta thalassemia
if impaired growth, paraspinal masses, severe bone changes, enlarging
liver and spleen
83. �In patients with cardiac disease, higher pre-
transfusion Hb level may be beneficial.
�Cardiac failure or very low Hb level (<5 gm/dl) =
aim to give only 5ml/kg of blood at any one
setting and transfuse at rate of <2 ml/kg/hr at
slower rate with diuretic (IV Frusemide 1mg/kg) at
the end of transfusion
84. Aim of Blood transfusions:
� Maximizing growth & development
� Minimizing extramedullary hematopoiesis &
decreasing facial & skeletal abnormalities
� Reducing excessive iron absorption from gut
� Retarding the development of splenomegaly &
hypersplenism
� Delaying the onset of complications
85. Blood Products for Transfusion
� Packed red cells
� Leukocyte depleted reds cells
� Neocytes ( <2 weeks old)
86. Iron chelation therapy
When to start chelation -
� 10-20 units transfused
� S. ferritin > 1000 ng/ml
� Age > 3 years old
96. Splenectomy
� Vaccination against encapsulated organisms should
be given 4 to 6 wks prior to surgery.
- Pneumococcal and Hib vaccinations
- Meningococcal vaccine required jn endemic areas
� After surgery, prophylactic oral penicillin should be
continued for prolong period at least up to the age of
15 yrs.
� Low dose aspirin (75mg daily) if thrombocytosis>
800,000mm3 after splenectomy
98. Management of complications
� Heart failure: Restriction of physical activity,
slow blood transfusion with diuretics, ACE
inhibitor, diuretics, beta blocker if
arrhythmia, combination therapy (DFO &
deferiprone)
� Hypothyroidism: Thyroxine
� Hypoparathyroidism: Calcium, vitamin D
99. � Osteoporosis: Regular blood transfusion, good
chelation, calcium, vit D, biphosphonates, sex
hormones (if associated with hypogonadism)
� Hypogonadism: Testosterone in boys & estrogen in
girls.
� Diabetes mellitus: Injection insulin
� Infections: Infections transmitted by Blood
Transfusion can be prevented by proper screening
blood before transfusion.
Other infections are managed accordingly.
103. Diet
▪ Foods with high iron contents should be avoided.
▪ Foods which decreases absorption of iron should
be taken.
▪ Milk & milk products, tea coffee should be taken
just after food.
▪ Vit E
▪ Zinc
▪ Iron supplementation should never be given to
Thalassemia patients.
104. Follow up
� Monthly
FBC, liver and spleen size
� Every 3 months
S. ferritin, glucose, urea, creatinine, SGPT
� Every 6 monthly
ECG, Echo
106. Prognosis
Thalassaemia major-life expectancy
• Without regular transfusion
– Less than 10 years
• With regular transfusion and no or poor iron
chelation
– Less than 25 years
• With regular transfusion and good iron
chelation
– 40 years, or longer?
The commonest cause of death is iron overload
112. � 8th May is the international Thalassemia Day. This
day is dedicated to Thalassemia, to raise public
awareness for prevention of Thalassemia and to
highlight the importance of clinical care for
Thalassemia patients in all countries.
Thalassemia Day
113. Take Home Messages...
� The key feature in all forms of thalassemia is microcytic hypochromic
anemia (which may be very mild in minor forms), but more severe forms may also
manifest with hemolysis, splenomegaly, delay in growth and development, and
skeletal deformities.
� Mandatory blood investigations has to be taken for confirmation and as a baseline
prior to transfusion.
� Management of G6PD mainly consists of preventing hemolysis by avoiding
triggers.
