ANAEMIA

DEFINITION

Anemia (An-without, emia-blood)

‘ Decrease in number of red blood cells (RBCs) or

less than the normal quantity of Haemoglobin in the
blood.is Condition called Anaemia’’
Red Blood
Cells
mature red blood cells are flexible biconcave disk and
Resembles a soft Ball Compressed b/w Two Fingers
2.4 million new erythrocytes are produced per
second.
It has a diameter about 8 micro meter and is flexible
that it can pass easily through capillaries
The membrane of RBC is very thin , so that gases such
as Oxygen and Co2 can diffuse easily across it
Cont
…
Mature Erythrocytes have No Nuclei
Immature Erythrocytes (RBC) are called
Reticulocytes which contain
remnants of nuclear material (reticulum).
Life Span of RBC – 120 days
RBC production process called Erythropoiesis In
erythropoiesis process , the most common
important hormone participates is
Erythropoietin ,
which produced from kidney
The entire process of Erythropoiesis typically takes 5
Days
RBC
Production
( Erythropoiesi
s)
 MCV
( Mean Corpuscular
Volume )
measure of the average RBC size
allows classification of anemia based on red cell
morphology

10 x HCT (%)
MCV ───────────────
RBC count (millions/mm3)..
 Cont
..
The normal range for MCV
80-99 fL(Femtoliter)

80-99 fL.
 MCHC
(Mean Corpuscular Hb
Concentration)

MCHC
 MCH
(Mean Corpuscular
Haemoglobin)
mean cell Hb.
mass of hemoglobin in an average RBC
MCH = Hb / RBC
Hb b
MCH ___
RBC

──
Cont
.. The normal range for MCH
27-31 picograms/cell

27 to 31 pg/cell
WHO Grading of
Anaemia
Grade 1 (Mild Anemia): 10 g/dl
Grade 2 (Moderate Anemia): 7-10 g/dl
Grade 3 (Severe Anemia): below 7 g/dl
Classificati
on
1. On The Basis of
Cause
A. Hypo proliferative (Resulting from Defective RBC
Production)

B. Haemorrhagic (Resulting from RBC Loss)

C. Haemolytic Anaemia (Resulting from

RBC Destruction)
2. On the Basis of
Morphology
A. Microcytic Anemia (Cells are smaller than
normal under 80 fl)

B. Macrocytic Anaemia (cells are larger than

normal over 100 fl)

C. Normocytic Anaemia (Cells are normal size 80–

100 fl)
1.Microcytic
Anaemia
It Occurs in Iron Deficiency Anaemia and ineffective
RBC production
a result of Haemoglobin synthesis failure/insufficiency.
Cells are smaller than normal under 80 fl
Heme synthesis defect
-Iron Deficiency Anaemia
Globin Deficiency Defect
- Thalassemia
2. Macrocytic
Anaemia
An Abnormally Large RBC
cells are larger than normal over 100 fl
It Occurs as Nutritional Deficiency.
E.g.Vit.B12 , Folates and Protein
It’s also occurs due to Drug toxicity
(phenytoin)
&
- Liver Disease & Alcohlism
- Hypothyrodism
- Chronic Haemolytic Anaemia &
Leukaemia
- Gastric Bypass surgery
3. Normocytic
Anaemia
overall Haemoglobin levels are decreased
but the red blood cell size(MCV) remains normal.
Cells are normal size 80–100 fl
Causes
 Acute blood loss

 Haemolytic Anaemia

 Aplastic Anaemia
TYPES OF
ANEMIA
CAUSE
S
Cont
.. Idiopathic
Hereditary Spherocytosis
Impaired RBC Production
- Deficiency of Nutrition
( Iron,Vit.B12,Vit.B6 )
- Decreased
Erythropoietin Production
Increased Destruction of RBC(Haemolytic)
-Abnormal Haemoglobin Synthesis (Thalassemia)
- Enzymatic Defect (Glucose-6-phosphate
Deficiency)
Cont
.. - Drugs Toxicity ( Primaquine & Phenytoin)
-Poisoning ( Lead Poisoning )
-Burns
- Splenomegaly
Due to Increased Blood Loss(Haemorrhagic)
-Acute (Trauma,Epistaxis,Scurvy,Hemophilia etc.)
-Chronic(Chronic Dysentry,Bleeding Piles,GI Haemorrhage
etc.)
ed RBC Production(Bone Marrow Depression)
- Hypoplasia ,Chronic Illness (Leukaemia & Nephritis)
- TB , Neoplastic Disease , Liver Disease
- Hypothyrodism
Pathophysiolo
gy
investigatio
ns
Anaemia
Diagnosis
complete blood count(CBC)
thorough evaluation of the patient
Physical examination and
medical history
1. CBC 9.Stool hemoglobin test
2. Peripheral blood smear
3. RBC indices 10. Bilirubin
4.Iron level 11.Lead level
5.Transferrin level 12.Reticulocyte count
6.Ferritin 13.LFT
7.Folate(Vitamin B9) 14.RFT
8.VitaminB12 15.Bone marrow biopsy
(Cyanocobalamin)
Cont
.. The red cell population is defined by
1. Quantitative parameters:
Volume of packed cells(PCV) i.e. the Hematocrit
Haemoglobin concentration
Red cell concentration per unit volume.

2. Qualitative parameters:

Mean corpuscular volume (MCV)

Mean corpuscular Haemoglobin (MCH)
Mean corpuscular Haemoglobin
concentration(MCHC)
Name Full Forms Normal Value

N rmal ue
PCV
o tfal
Packed Cell
Volume s
33 to 45 %

RBC Red Blood Cells 3.9 to 5.03

MCV Mean 80 to 100 fL
Corpuscular
Volume
MCH Mean 27 to 31 Pg/cell
Corpuscular Hb
MCHC Mean 32 to 35 g/dl
Corpuscular Hb
Concentration
Reticulocytes - 0.8 to 2.2 %
Count
RDW Red Cell 12 to 14.5 gm/dl
Distribution Width
Cont
… Vitamin B12 Cobalamin 200to 500 Pg/ml
S. Iron Iron 65 to 150 Microgram
S. Billirubin - 0.2 to 1.2 mg/dl
SGPT Serum Glutamic Pyruvic 10 to 50 IU/L
Transminase
SGOT Serum Glutamic 10 to 40 IU/L
Oxaloacetic
Transminase
TIBC Total Iron Binding 250 to 370 mg/dl
Capacity
Haemoglobin - 12.5 to 15gm/dl
TC Total Count 4000 to 1000 Cu/mm
SIGNS &
SYMPTOMS
Brittle nails
Koilonychia (spoon shaped nails)
Atrophy of the papillae of the tongue
Angular Stomatitis
Brittle hair
Dysphagia and Glossitis
Plummer vinson Syndrome /kelly patterson
Syndrome ( Dysphagia with Iron Deficiency
Anaemia)
Koilonych
ia
Angular
Cheilitis
Splenomeg
aly
Anemic
eyes
Pallo
r
1.IRON DEFICIENCY
ANEMIA
Anaemia associated with either Inadequate
Absorption or Excessive Loss of Iron/Blood.

It is Chronic Microcytic Anaemia.

The most common Cause of Anaemia in Children is

Iron Deficiency Anaemia.It’s most common cause by
Microcytic Hypochromic Anaemia.
Iron metabolism
 Most of the iron in the food is in the form of ferric
ion but it is ferrous form that is absorbed in the
proximal small intestine.To maintain positive iron
balance in childhood about 1mg of iron must be
absorbed .About 20% of iron is absorbed from the
diet so a diet containin 8-10mg of iron must be
consumed each day.
 Ferric ion coverts into ferrous by ferric reductase.
 All the iron absorption occur in the
duodenum,transport of ferrous into enterocytes by
divalent metal transporter(DMT1)
 Some of iron is stored in ferritin and remaining is
transported out of the enterocytes by ferroportin1, a
protien called hephaesitin is associated with it
present on the basolateral side.
 In plasma ferrous is converted to ferric and
transported by transferrin protien.
ETIOLOGY
 Low birth weight and perinatal haemorrhage
 Causes of chronic iron deficiency anaemia are:
 Lesions of GI tract(peptic ulcer,Meckel diverticulum,polyps,
hemangioma,inflammatory bowel diseases.)
 Hookworm infestations.
 Pulmonary hemosiderosis
 MILK ALLERGY-due to lactase deficiency.
 Histological abnormalities of mucosa of GI tract.
 Caus
es Iron Supply at Birth
Insufficient
Impaired Iron Absorption
Blood Loss
Insufficient Iron Intake in Diet
Periods of Rapid Growth
Sign &
Symptoms
Decreases Serum Iron Level
Decreased Hb Level (6 to 9 mg/dl)
Cold Hands and Feet
Shortness of breath
Fatigue
Sore Tongue
Brittle
Nails
Irritability
Pale Skin Colour
Dizziness
 CLINICAL MANIFESTATIONS
 Clinical findings are related to severity and rate of
development of anaemia.
 Pallor is the most important sign of iron deficiency.
 Irritability and anorexia usually precede weakness,fatigue,leg
cramps,breathlessness and tachycardia.it occures when Hb
level falls below 5g/dl
 Congestive cardiac failure,splenomegaly may occur with
severe untreated anaemia.
 Angular stomatitis.glossitis,koilonychia and platynychia are
noted in severe cases.
 In some children ingestion of lead leads to
PLUMBISM.
 Iron def.anaemia may have effects on neurological and
intellectual function
 Children with iron def.anemia may be obese or
MANAGEMENT
 INVESTIGATION-
 A careful dietary history is important,including the type
of milk and weaning foods in infants and the use of
supplements.
 Peripheral blood smear reveals microcytic hypochromic
red cells,with anisocytosis and poikilocytosis and
increased red cell distribution width.
 MCV and MCH are reduced.total serum iron and ferritin
are reduced while the total iron binding capacity is
increased.
 Saturation of transferrin is reduced to less than 16%..
Red cell birth 0.5-2yr 6-12yr 12- 12-18
indices 18yr(girl yr(boys)
s)
MCV 108 78 86 90 88
MCH 34 27 29 30 30
MCHC 33 33 34 34 34
RDW 12.8+_1. - - - -
2%
SERUM 10- - - - -
IRON 30umol/l
SERUM 15- - - -
FERRITI 300ng/m -
N l(boys)1
5-
200ng/m
l(girls)

TOTAL 250- - - - -
IRON 400ug/m
BINDIN l
G
CAPAC
I TY
High free erythroprotoporphyrin…
Reticulocyte count can be increased or
decreased,normal RC is 2-6%in newborns and 0.5-2%
in children.RC should be corrected for degree of
anaemia..
Corrected RC=RC X Actual hematocrit/normal
hematocrit
LOW RC
-Congenital or acquired anaemia,aplastic or
hypoplastic anaemia.
Pure red cell aplasia
Parvovirus B19 infection
HIGH RC
Hemolysis, hemorrhage,iron def. after
treatment,sepsis
 TREATMENT
Oral therapy-
Patients with iron def. anaemia should receive 3-
6mg/kg per day of elemental iron in 3 divided
doses.Ferroussalts (sulphates,fumarates,gluconate)
Absorption is better when taken on an empty
stomach or in between meals
About 10-20 % patients develop gastrointestinal
side effects such as nausea,epigastric
discomfort,vomiting,constipation and diarrhea.
Enteric –coated preparations have fewer side
effects but are less efficacious and more
expensive
Parenteral therapy—
Indications–
Intolerance to oral iron
Malabsorption on going blood loss at a rate
where oral replacement cannot match iron loss.
IV Iron sucrose is safe and effective and is
commonly used for children IBD and end
stage renal disease
The dose is 1-3mg/kg diluted in 150ml of NS
and given as slow infusion over 30-90 min.
Total dose of parenteral iron can be calculated
as
–
iron required(mg)=wt./kg x 2.3x(15-hb in g/dl) +
500 or 1000mg(for iron stores)
Blood transfusions—
Red cell transfusions are needed in emergency
situations such as acute severe
hemorrhage,severe anaemia and cogestive
cardiac failure but should be given at a very slow
rate with hemodynamic monitoring
Differential diagnosis—
Iron deficiency anaemia must be differentiated
from other causes of microcytic hypochromic
anaemia—
 Thalassemia (α&β)
 Other Hb pathies
 Anaemia of chronic disorders
 Lead poisoning
2.MEGALO-BLASTIC ANAEMIA
 Definition: Macrocytic Anemia

macrocytic anemia MCV>100fL

Impaired DNA formation due to lack of:
 B12 or folate in ultimately active form
 use of antimetabolite drugs
Macrocytosis also caused by
 Liver disease with inadequate cholesterol esterification
 Alcohol abuse independent of folate (MCV 100-105)
 Myelodysplasia
 Post-splenectomy
 HIV drugs
 Dilantin
 Vitamin B12: Cobalamin

Meat and dairy products only

Minimum daily requirement 6-9 mcg/d
Total body store 2-5 mg (half in liver)

Helps to synthesize thiamine, thus deficiency leads

to problems with DNA replication
 B12: Cobalamin absorption

 Initially bound to protein in

diet, liberated by acid and
pepsin, then binds to R factors
in saliva and gastric acids
 Freed from R factors by
pancreatic proteases then
binds to Intrinsic Factor
secreted by gastric parietal cells
 Absorbed together (Cbl + IF) in
ileum
 Released from IF in ileal cell
then exocytosed bound to
trans-Cbl II
 Cbl bound to transcobalamin II
binds to cell surface receptors
and is endocytosed
Actions of Cobalamin & Folate
 Causes of B12
Deficiency:
Pernicious Anemia
Autoantibody to Intrinsic Factor detectable in <70%
 Highly specific, but insensitive
 2 types of anti-IF antibody
 Blocks attachment of Cbl to IF
 Blocks attachment of Cbl-IF complex to ileal receptors
Chronic atrophic gastritis
 Autoantibody against parietal cells (H-K-ATPase) though
pathology indicates destruction by CD4+ T cells
 Increased risk of gastric cancer (carcinoid and intestinal-
type)
 Causes of B12 Deficiency:
Growing Older
Usually mild and subclinical
Age >65 approx 5%
Age >75 approx 10%+, up to 40% in institutionalized
patients
Unclear mechanism
 gastric atrophy
 inadequate intake
 Achlorhydria
 Causes of B12 Deficiency:
Surgery, Medication, Worms, Etc.
 Gastrectomy/Bariatric surgery
 Ileal resection or bypass
 Ileal disease (TB, lymphoma, amyloid, post-radiation, Crohn’s)
 Enteropathies (protein losing, chronic diarrhea, celiac sprue)
 Fish tapeworm (Diphyllobothrium latum) infection
 Bacterial overgrowth
 HIV infection
 Chronic alcoholism
 Sjogren’s syndrome
 Pancreatic Exocrine Insufficiency
 Strict vegetarian diet
 Inherited
 Trans-Cbl II or IF deficiency
 decreased uptake of IF-Cbl (Imerslun-Grasbeck’s or juvenile megaloblastic anemia) - also presents
with proteinuria
 Homocysteinuria, severe abnormalities of methionone synthesis, abnormal lysosomal exporter
 Decreased absorption from medication
 Neomycin
 Metformin (biguanides) up to 10-25%
 PPI
 Nitric oxide (inhibits methionine synthase)
 B12 Deficiency Symptoms
 Atrophic glossitis (shiny
tongue)
 Shuffling broad gait
 Anemia and related sx
 Vaginal atrophy
 Malabsorption
 Jaundice
 Personality changes
 Hyperhomocysteinemia
 Neurologic symptoms (next
slide)
 Copper deficiency can
cause similar neurologic
symptoms
 B12 Symptoms: Neurologic

 Paresthesias  Subacute combined degeneration of

 Memory loss the dorsal (posterior) and lateral
 Numbness spinal columns
 Weakness  Due to a defect in

 Loss of dexterity due to loss of

myelination
vibration and position sense
 NOT ALL PATIENTS WITH B12
 Symmetric neuropathy
DEFICIENCY RELATED NEUROLOGIC
legs>arms ABNORMALITIES ARE ANEMIA OR
 Severe weakness, spasticity, clonus, MACROCYTOSIS
paraplegia and incontinence
Subacute
Combined
Degeneration

Degeneration and demyelination of the

dorsal (posterior) and lateral spinal
columns
 B12 Lab findings
 Macroovalocytic anemia
with elevated serum bili
and LDH
 Increased red cell
breakdown due to
ineffective hematopoiesis
 Reticulocytes, WBC &
platelets normal to low
 Hypersegmented
neurophils
 Also occur in
renal failure,
iron deficiency,
inherited
Bone Marrow
Hypercellular marrow
 Megaloblastic erythroid
hyperplasia
 Giant metamyelocytes

Due to slowing of DNA

synthesis and delayed
nuclear maturation
Methionine deficiency may
play a central role
 Folate

SOURCE:Animal products (liver), yeast and leafy

vegetables
Normal requirement 400mcg/day
Pregnancy/Lactation: 500-800mcg/day
Increased requirement in hemolytic anemia
and exfoliateive skin disease
Body stores: 5-10mg
 Folate Metabolism

Binds to folate
receptor, becomes
polyglutamated
intracellularly
Many drugs
(trimethoprim,
methotrexate,
pyrimethamine)
inhibit dihydrofolate
reductase
 Causes of Folate Deficiency

Malnutrition: Destroyed by heat during cooking

Alcoholism (decreased in 2-4 days): impairs
enterohepatic cycle and inhibits absorption
Increased requirement in hemolytic anemia,
pregnancy, exfoliative skin disease
IBD, celiac sprue
Drugs
 Trimethoprim, Methotrexate, Pyrimethamine
(inhibit DHFR)
 Phenytoin: blocks FA absorption, increases utilization
(mech unknown)
 Folate deficiency symptoms

Similar symptoms as B12 except for neurologic

symptoms
Presentation is different classically:
 Alcoholic
 Very poor dietary intake
 Older
 Depressed
 Living alone
Whom should you test for B12 or Folate deficiency?

MCV >100 with or without anemia

Hypersegmented neutrophils
Pancytopenia of uncertain cause
Unexplained neurologic symptoms
Alcoholics
Malnourished, particularly the elderly
Diabetics on metformin with new onset neuropathy
 Lab testing for diagnosis

Serum B12 Serum MMA Homocystein

Folate e
Normal >300 pg/mL >4 ng/mL 70-270 5-14
Deficiency <200 pg/mL <2 ng/mL
Confirm B12 200-300 High High
Confirm folate 2-4 Normal High

High amount of seaweed in the diet can interfere with the B12 assay as
can a single meal. It is best to add-on tests to blood already in the lab,
particularly for inpatients due to the variability of the test.

Intrisic factor antibody assay can be falsely positive if pt has recently

received a B12 shot with B12 >800, thus important to add-on.
 Shilling Test

1. PART 1: Oral labeled B12 and

IM unlabeled B12 at the same
time to saturate tissue stores
2. 24h urine to assess absorption
>5% normal
<5% impaired
3. PART 2: Repeat w/oral IF
if now normal =PA
if abnormal = malabsorption
4. Can continue with antibiotics to
look for bacterial overgrowth,
pancreatic enzymes for Part 1 test result Part 2 test result Diagnosis
Normal
exocrine insufficiency Normal - or vitamin B12
deficiency
Pernicious
Low Normal
anemia
Low Low Malabsorption
 B12 Deficiency: Treatment

IM B12 1000mcg daily x 1 wk

 then 1000mcg weekly x 1 month
 Then 1000mcg monthly for life for PA
Oral high dose 1-2 mg daily
 As effective but less reliable than IM
 Currently only recommended after
full parenteral repletion
Sublingual, nasal spray and gel formulations
available
 Vegan B12 Recommendations

Daily multivitamin with 10mcg/d

Available in a few specific commercial nutritional
yeasts most of which contain B12 from
Pseudomonas sp., Propionibacterium sp. or
Streptomyces sp.
Probiotics are NOT sufficient to provide
adequate B12
Keep supplements in the fridge and out
of light
 Folate Deficiency Treatment

Oral folate 1mg daily for 4 months or until

hematologic recovery
Rule out B12 deficiency prior to treament as folic
acid will not prevent progression of neurologic
manifestations of B12 deficiency
Repeat testing for B12 deficiency may be
reasonable for those on long-term folic acid
therapy if hematologic (macrocytosis or ↑LDH) or
neurologic sx persist
3.HAEMOLYTIC ANAEMIA

 It is defined as
1) Premature destruction of red cells and a shortened red cell life
span below normal 120 days
2) Elevated erythropoietin levels and a compensatory increase in
erythropoiesis
3) Accumulation of hemoglobin degradation products released by red
cell breakdown derived from haemoglobin
CLASSIFICATION
ACQUIRED HAEMOLYTIC ANAEMIA

 IMMUNE HAEMOLYTIC ANAEMIA

These can be subdivided into:

a) Autoimmune
b) Alloimmune
c) Drug-induced
AUTOIMMUNE HAEMOLYTIC ANAEMIA

Caused by antibodies produced by patient’s own

immune system
 Classified according to thermal properties of antibodies:

 warm antibodies bind to RBC most avidly at 370C

 cold antibodies bind best below 320C
Warm AIHA:
Antibody usually IgG, but may be IgM or IgA
Usually facilitate sequestration of sensitized RBCs
in spleen
May be primary or secondary –
 autoimmune disorders, HIV,
 chronic lymphocytic leukaemia (CLL),
 non-Hodgkin's lymphoma (NHL)
Most common type
Incidence:

Occurs in either sex but female

preponderance reported esp. primary
Occurs in all ages

Higher incidence of secondary noted in patients > 45

years
Clinical Features:

Hemolytic anaemia of varying severity

Tends to remit and relapse
Symptoms of anaemia
Jaundice
Splenomegaly
Symptoms of underlying disorder (if 20
Laboratory Features:

Variable anaemia
Blood film: polychromasia, microspherocytes
Severe cases: nucleated RBCs, RBC fragments
Mild neutrophilia, normal platelet count
Evan’s syndrome: association with ITP(immune
thrombocytopenia)
Bone marrow: erythroid hyperplasia; underlying
lymphoproliferative disorder
Unconjugated hyperbilirubinaemia
Haptoglobin levels low
Urinary urobilinogen usually increased; haemoglobinuria
uncommon
Serological Features
Direct antiglobulin test (DAT; Coomb's test) usually
positive
DAT: rabbit antiserum to human IgG or complement C3
(Coomb's reagent) added to suspensions of washed
RBCs. Agglutination signifies presence of surface IgG or
complement
RBC may be coated with
 IgG alone
 IgG and complement
 complement only
Rarely anti-IgA and anti-IgM encountered
Treatment:
 Remove/treat underlying cause
 Corticosteroids - high doses then tapering when PCV stabilizes
 Splenectomy:
 patients who fail to respond to steroids
 unacceptably high doses of steroids to maintain adequate
PCV
 unacceptable side-effects
 Transfusion
 Immunosuppressive Drugs:
 Azathioprine
 Cyclophosphamide (CTX)
 Others:
 plasmapheresis
 Intravenous immunoglobulin (IVIG)
 Androgens e.g. danazol
Cold AIHA:

• Two major types of cold antibody:

1) Cold agglutinins
2) Donath-Landsteiner antibodies
Causes either immediate intravascular destruction of
sensitized RBCs by complement-mediated mechanisms
or sequestration by liver (C3 coated RBCs preferentially
removed here)
Cold Agglutinins:

IgM autoantibodies that agglutinate RBCs

optimally between 0 to 50C. Complement fixation
occurs at higher temperatures
Primary - Cold Haemagglutinin Disease (CHAD)
or secondary (usually due to infections)
Peak incidence for CHAD > 50 years
Primary usually monoclonal;
 secondary usually polyclonal
Pathogenesis:

Specificity usually against I/i antigens

Varying severity depending on:
 titre of antibody in serum

 affinity for RBCs

 ability to bind complement
 thermal amplitude
Bind red cells in peripheral circulation impeding capillary
flow, producing acrocyanosis
Clinical Features:

Chronic haemolysis; episodes of acute haemolysis

can occur on chilling
Acrocyanosis frequent; skin ulceration and necrosis
uncommon
Mild jaundice and splenomegaly
Secondary cases e.g. Mycoplasma infection, self-
limited
Laboratory Features:
Anaemia- mild to moderate
Blood film:
a) agglutination,
b) spherocytosis less marked than warm AIHA

DAT +ve: complement only

Anti-I: idiopathic disease, mycoplasma, some
lymphomas
Anti-i: infectious mono, lymphomas
Treatment:

Keep patient warm

Treat underlying cause
Alkylating agents: chlorambucil, CTX
Splenectomy and steroids generally not
helpful
Plasmapheresis- temporary relief
Transfusion- washed packed cells
Paroxysmal Cold Haemoglobinuria
Donath-Landsteiner syndrome
Rare form of haemolytic anaemia
Characterized by recurrent haemolysis following
exposure to cold
Formerly, more common due to association
with syphilis
Self-limited form occurs in children following
viral infections
Antibodies usually IgG with specificity for P
antigen
Biphasic:
Drug-induced Haemolytic Anaemia

May cause immune haemolytic anaemia by

three different mechanisms:
1) Neoantigen type e.g. Quinidine
2) Autoimmune mechanism e.g.  - Methyldopa
3) Drug adsorption mechanism e.g. Penicillin
Drug adsorption mechanism
Also known as hapten mechanism
1) Drug binds tightly to red cell membrane
2) Antibody attaches to drug without direct
interaction with RBC
Usually seen in patients receiving high doses of
penicillin – substantial coating of RBC with
drug
Small proportion develop anti-penicillin
antibody binds to drug on RBC
DAT +ve and haemolysis may ensue
Occurs after 7-10 days of treatment
Neoantigen type
Formerly known as immune complex /
innocent bystander
 theory suggested drug formed immune complex
with anti-drug antibody
a) attached non-specifically to red cell
b) destruction by complement
Above interaction required component of red cell
membrane to bind to antigen recognition site on
antibody
Autoimmune mechanism

Antibody binds to red cell membrane antigens

Alpha-methyldopa responsible for most cases
DAT becomes +ve in 8-36% of patients taking drug
However, only 0.8% of patients develop clinical
haemolysis
Induces auotimmune red cell antibodies by
unknown mechanisms
Non-immune haemolytic anaemias:

Non-immune haemolytic anaemias:

 Paroxysmal nocturnal haemoglobinuria (PNH)
 Red cell fragmentation syndromes
 March haemoglobinuria
 Infections
 Chemical and physical agents
 Secondary haemolytic anaemia
4.Aplastic
Anaemia
Aplastic Anaemia is Rare and Serious Blood Disorder
in which Bone Marrow Stops making Enough New
Blood Cells.
This is Because The Bone Marrow’s Stem Cells are
Damaged.
The Disorder tends to get Worse over Time,Unless
it’s cause is Found and Treated.
Resulting Pancytopenia ( Insufficient Numbers of
RBCs,WBCs and Platelets)
Caus
es
Exposure to Toxic Substances such as Arsenic,
Benzene
Cancer Therapy
Use of Certain Drugs
Autoimmune disorder such as Rheumatoid Arthritis
Viral Infection such as Hepatitis, HIV etc.
Damage to the Stem Cells in Bone Marrow that are
Responsible for Blood Cell Production.
Weakend Bone Marrow (Hypo parathyrodism)
Sign &
Symptoms
Pancytopenia
Fatigue and Restlessness
SOB
Hypoxemia
Irregular Heartbeat
Heart Murmur
Pale Skin , Gums
and Nail beds
Fever and
Frequent Infection
due to
Leukocytopenia
Management
Blood Transfusion
BMT OR Stem cells Transplantation
Medicines :
 Erythropoietin to Stimulates The Bone
Marrow
 Antibiotic & Anti Viral Medicines to Prevent & Treat
Infection
Avoid Exercise
Avoid Contact Sports
Avoid Infections
5.Sickle cell anemia
Sickle Cell Anaemia is Serious Inherited Disease
RBC that assume an abnormal, rigid, sickle shape
Sickling decreases the cells' flexibility and results in a
risk of various complications.
The sickling occurs because of a mutation in the
hemoglobin gene
Cont
…
Sickle cells contain abnormal hemoglobin called
sickle hemoglobin or hemoglobin S. Sickle
hemoglobin causes the cells to develop a sickle, or
crescent, shape.

Sickle cells are stiff and sticky. They tend to block

blood flow in the blood vessels of the limbs and
organs. Blocked blood flow can cause pain and organ
damage. It can also raise the risk for infection.
Sickle cell
anemia
Sign &
Symptoms
The most common symptom of anemia is fatigue.
Other signs and symptoms of anemia include:
 Shortness of breath
 Dizziness
 Headaches
 Coldness in the hands and feet
 Paler than normal skin or mucous membranes
 Jaundice
Management

The goal of treatment is to manage and control symptoms, and

to limit the number of crises. People with sickle cell disease
need ongoing treatment, even when not having a crisis.
People with this condition should take folic acid supplements.
Folic acid helps make new red blood cells. Blood
transfusions (may also be given regularly to prevent stroke)
Pain medicines
Plenty of
fluids
Cont
…
Antibiotics, which help prevent bacterial infections that are common
in children with sickle cell disease
Medicines that reduce the amount of iron in the body People with
sickle cell disease should have the following vaccinations to lower the
risk of infection:
Haemophilus influenzae vaccine (Hib) Pneumococcal
conjugate vaccine (PCV) Pneumococcal polysaccharide
vaccine (PPV)