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APPROACH TO CONGENTAL

HEMOLYTIC ANEMIAS
Dr. Somendra Shukla
Fellow Neonatology
Other questions to guide you


Is this acute or chronic? Is this acute or chronic?
Is there a family history? Is there a family history?
Does the child appear ill, or have signs of Does the
child appear ill, or have signs of systemic disease?
systemic disease?
Are the liver and spleen large? Are the liver and
spleen large? (extramedullary extramedullary sites of
sites of hematopoiesis hematopoiesis)
Exposure to infectious disease: HIV, Exposure to
infectious disease: HIV, malaria, dengue malaria,
dengue

But first, is there really anemia?
• Anemia: Central venous hemoglobin < 13 g/dL
or capillary hemoglobin < 14.5 g/dL in infant >
34 weeks and 0-28 days old

The Three Primary Measures
Measurement
A. RBC count (RCC) 5 million
B. Hemoglobin 15 g%
C. Hematocrit (PCV) 45

A x 3 = B x 3 = C - This is the rule of thumb
Check whether this holds good in a given result
If not -indicates micro or macrocytosis or hypochro.
The Three Derived Indices
easurement Normal
A. RCC 5 million
B. Hemoglobin 15 g%
C. Hematocrit 45 %

MCV C ÷ A x 10 = 90 fl
MCH B ÷ A x 10 = 30 pg
MCHC (%) B ÷ C x 100 = 33%
Anemia – Second Test
RETICULOCYTE COUNT %
Normal
Less than 2%
• ‘RBC to be’ or Apprentice RBC
• Fragments of nuclear material
• RNA strands which stain blue
Reticulocyte
No definite nucleus
Reticulum of RNA
Deep blue staining
Light blue cytoplasm
Cell size about 10 µ
Reticulocytes
Leishman’s Supravital
Reticulocyte Production Index
For example, the RPI is calculated as follows
Reticulocyte count 9%
Hb content 7.5 g%
1. Correction for Anemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %
2. Correction for life span
4.5 ÷ 2 = 2.25 %
3. Thus, the RPI is 2.25
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Anemia
Hypoproliferative
Hemolytic
RPI < 2 RPI > 2
The Reticulocyte production index (RPI, also called
a corrected reticulocyte count)

•raw reticulocyte count is misleading in anemic patients.
•reticulocyte count is not really a count but rather a percentage:
it reports the number of reticulocytes as a percentage of the
number of red blood cells.
•In anemia, the patient's red blood cells are depleted, creating
an erroneously elevated reticulocyte count
www.drsarma.in
Workup – Third Test
• The next step is ‘What is the size of RBC’ ?
• MCV indicates the Red cell volume (size)
• Both the MCH & MCHC tell Hb content of RBC
• If the RPI is 2 or less
• We are dealing with either
– Hypoproliferative Anemia (lack of raw material)
– Maturation defect with less production
– Bone marrow suppression (primary/ secondary)
www.drsarma.in
Mean Cell Volume (MCV)
• RBC size is measured indirectly by
• The Mean Cell Volume (MCV) and RDW
Microcytic
< 80 fl
MCV
Normocytic Macrocytic
80 -100 fl > 100 fl
< 6.5 µ 6.5 - 9 µ > 9 µ
www.drsarma.in
Anemia Workup - MCV
Microcytic
MCV
Normocytic Macrocytic
Iron Deficiency (IDA)
Chronic Infections
Thalassemias
Hemoglobinopathies
Sideroblastic Anemia
Chronic diseases, CKD
Early IDA
Hemoglobinopathies
Primary marrow disorders
Combined deficiencies
Increased destruction
Megaloblastic anemias
Liver disease/alcohol
Hemoglobinopathies
Metabolic disorders
Marrow disorders
Increased destruction
Presentation of hemolytic anemia
• Jaundice is usually the first symptom
• Compensatory reticulocytosis
• Pallor presents after 48 hours of age
• Unconjugated hyperbilirubinemia of > 10-12
mg/dL
• Tachypnea and hepatosplenomegaly may be
present

Hemolytic Anemia

• Definition:
– Those anemias which result from an increase in
RBC destruction

• Classification:
– Congenital / Hereditary
– Acquired

Laboratory Evaluation of Hemolysis
Extravascular Intravascular

HEMATOLOGIC
Routine blood film
Reticulocyte count
Bone marrow
examination
Polychromatophilia

Erythroid
hyperplasia
Polychromatophilia

Erythroid
hyperplasia

PLASMA OR SERUM
Bilirubin
Haptoglobin
Plasma hemoglobin
Lactate dehydrogenase
Unconjugated
, Absent
N/
(Variable)
Unconjugated
Absent

(Variable)

URINE
Bilirubin
Hemosiderin
Hemoglobin
0
0
0
0
+
+ severe cases

Inherited or acquired:

• Inherited HA are usually caused by intrinsic
defect.
• While acquired HA are caused by an extrinsic
defect.
• However there are some exceptions: Paroxysmal
nocturnal haemoglobinuria (PNH) which is an
acquired intrinsic defect, and severe
hereditaryG6PD enz deficiency which requires
the presence of an extrinsic trigger such as the
antimalarial drug for the intrinsic defect to
manifest.

Hemoglobinuria
Classification of Hemolytic Anemias
Hereditary


1. Abnormalities of RBC interior
a.Enzyme defects: G-6-PD def,PK def
b.Hemoglobinopathies
2. RBC membrane abnormalities
a. Hereditary spherocytosis etc.
b. PNH



Acquired c. Spur cell anemia
3. Extrinsic factors
a. Hypersplenism
b. Antibody: immune hemolysis
c. Mechanical trauma: MAHA
d. Infections, toxins, etc



Ref : Harrison’s
Features of HEMOLYSIS
Bilirubin
LDH
Reticulocytes, n-RBC
Haptoglobulins
+ve Urinary hemosiderin, Urobilinogen

Blood Film

Spherocytes No spherocytes Fragmentation

DCT +ve DCT –ve

AI Hemolysis H. Sherocytosis Malaria,
Clostidium
Hereditery enzymopathies Microangiopathic,
Traumatic

Red Cell Membrane Defects
1.Hereditary Spherocytosis
– Usually inherited as AD disorder
– Defect: Deficiency of Beta Spectrin or Ankyrin 
Loss of membrane in Spleen & RES becomes
more spherical Destruction in Spleen

RBC Membrane
–C/F:
• Asymptomatic
• Fluctuating hemolysis
• Splenomegaly
• Pigmented gall stones- 50%

Complications
• Clinical course may be complicated with Crisis:
– Hemolytic Crisis: associated with infection
– Aplastic crisis: associated with Parvovirus infection
• Inv:
– Test will confirm Hemolysis
– P Smear: Spherocytes
– Osmotic Fragility: Increased


Screen Family members

Osmotic Fragility
• Management:
– Folic Acid 5mg weekly, prophylaxis life long
– Spleenectomy
– Blood transfusion in Ac, severe hemolytic crisis

2.Hereditary Elliptocytosis
• Equatorial Africa, SE Asia
• AD / AR
• Functional abnormality in one or more anchor
proteins in RBC membrane- Alpha spectrin , Protein
4.1
• Usually asymptomatic
• Mx: Similar to H. spherocytosis
• Variant:
3.SE-Asian ovalocytosis:
• Common in Malaysia , Indonesia…
• Asymptomatic-usually
• Cells oval , rigid ,resist invasion by malarial parasites

Elliptocytosis
Red Cell Enzymopathies
• Physiology:
– EM pathway: ATP production
– HMP shunt pathway: NADPH & Glutathione
production
1. Glucose-6-Phosphate Dehydrogenase (
G6PD ) Deficiency
–Pivotal enzyme in HMP Shunt & produces NADPH
to protect RBC against oxidative stress
–Most common enzymopathy -10% world’s
population
–Protection against Malaria
–X-linked

(Oxidised form)
(Reduced form)
• Clinical Features:
– Acute drug induced hemolysis:
• Aspirin, primaquine, quinine, chloroquine, dapsone….
– Chronic compensated hemolysis
– Infection/acute illness
– Neonatal jaundice
– Favism

• Inv:
–e/o non-spherocytic intravascular hemolyis
–P. Smear: Bite cells, blister cells, irregular
small cells, Heinz bodies, polychromasia
–G-6-PD level

• Treatment:
–Stop the precipitating drug or treat the
infection
–Acute transfusions if required
2. Pyruvate Kinase Deficiency
–AR
–Deficient ATP production, Chronic hemolytic
anemia
–Inv;
• P. Smear: Prickle cells
• Decreased enzyme activity
–Treatment:
• Transfusion may be required