Hemolytic anemia

DEFINITION
Those anemias which result from an increase in RBC
destruction coupled with increased erythropoiesis

It shares the features :

•A shortened RBC life span to less than 120 days

•Elevated erythropoietin level – erythropoiesis
•Accumulation of hemoglobin degraded products
 Pathogenesis
(Red cell destruction)
• Takes place within macrophages which are abundant in
RE system
• Triggered by age dependent red cell surface proteins
leading to their recognition and phagocytosis

• Red cell destruction – 2 mechanisms

1.Intravascular hemolysis
2.Extravascular hemolysis
Clinical features
Depends on severity and duration of hemolysis
Pallor
Jaundice
Splenomegaly
Dyspnoea
Tachycardia and systolic murmur
Gall stones and leg ulcers
Skeletal abnormalities
Hemolytic facies – chipmunk facies
Investigations
History
Peripheral blood film
Bone marrow findings
Biochemical tests
Screening tests
Peripheral blood film
Morphological findings
•Polychromatophilia, nucleated RBC, thrombocytosis,
neutrophilia

Morphological abnormalities
•Spherocytes, sickle cell, target cell, schistocytes,
acanthocytes
Polychromatophilia Nucleated RBC
Sickle cell Thalassemia
 Bone marrow findings
• Erythroid hyperplasia

• Reticulocytosis
5 % infancy
1 % after 1 year
Normal bone marrow Erythroid hyperplasia
Biochemical tests
Other tests
• Sickling test - sodium metabisulphite
• Osmotic fragility test
• HB Electrophoresis
HB ELECTROPHORESIS
Classification of hemolytic Anemia
CLASSIFICATION OF HEMOLYTIC
ANEMIA Intracarpuscular defects
• Red cell enzyme deficiency- G6PD deficiency,
Pyruvate kinase deficiency
• Hereditary defects of red cell membrane -
Hereditary spherocytosis, Elliptocytosis
• Ineffective erythropoiesis - Thalassemia
• Haemoglobinopathies - Sickle cell and
Hb C,D or E Diseases
• Paroxysmal nocturnal haemoglobinuria
 EXTRA CARPUSCULAR DEFECTS

• Immune haemolytic anemia - Rh,ABO incompatability

• Infections – Malaria, Kala azar,
• Schistocytic - DIC, HUS
 Haemoglobins

Hb A [alpha 2, beta2]
Hb F [a2, gamma2]
Hb A2 [a2 , delta2 ]
 VARIOUS TYPES OF
HAEMOGLOBINS
• Hb A1:Alfa 2 ,Beta2 -Adult
• Hb A2 :Alfa2 , Delta2-Adult
• Hb F: Alfa2, Gama2-Fetal
• Gower I: Zeta2,Epsilon2-Embryonic
• Gower II: Alfa2, Epsilon2-Embryonic
• Portland I: Zeta2,Gama2-Embryonic
• Portland II: Zeta2, Beta2-Embryonic
 BETA THALASEMIA

Beta chain production is either partially or

Totally reduced. So excess of alpha chains
get precipitated in RBC.
Types
THALASSEMIA MAJOR
Clinical features
• Infants born normally
• Increasing pallor with age and may
need transfusion around 6 months of
age
• Mild icterus
• Hepatosplenomegaly
• Mangoloid facies in infants survived the
first year of life
• Bossing of the skull
• Prominent frontal /parietal bones
• prominent malar eminence
• Depressed bridge of nose
Course of disease

• Depends on severity and treatment received

• IF no treatment received child may die during first few
years of life due to anemia and related complications
• If received transfusions child may succumb during
second decade of life with complications of iron
overload
• If iron overload is also taken care of ,they can lead near
normal life
X – RAY SKULL
Hair on end appearance
MANAGEMENT

• Packed red cell transfusions

• Chelation Therapy
 TRANSFUSION THERAPY
• As soon as diagnosis firmly established
• If Hb drops < 7 gms%, regular transfusion regimen
• Maintain Hb level 10-12gm/dl to prevent ill effects of anemia (hyper
transfusion)
• May require 10-15ml/kg every 2-3 weeks
• Transfusion with Group, type specific, triple saline washed packed cells is
preferable.
PREVENTION OF TRANSFUSION TRANSMITTED
INFECTIONS

• Stringent Donor Selection

• Hepatitis B Vaccination
• Good screening for HIV, HbsAg And HCV
• Malaria– Prevention
• CMV – Leuco depletion.
 SPLENECTOMY

• INDIACATIONS FOR SPLENECTOMY

– Transfusion requirement exceeds 250 ml/kg/year of PCV
– Defer in children < 6years of age
Pneumococcal & Hib vaccines given before splenectomy
Life long post-splenectomy penicillin prophylaxis is advised
 CHELATION THERAPY

• Iron Overload
• Excess GI absorption
• Lack of excretory mechanism for excess iron in the body
- Chronic red cell transfusions
• Effects of iron overload(secondary haemochromatosis)
• Iron deposit in Liver, spleen, heart, endocrine glands and leads to their mal
function

• Drugs used presently

– Desferrioxamine (Injectable)
– Deferiprone (Oral )
Newer therapies approaches

• Bone marrow transplantation

• Stem Cell Transplant
• Sources
• Bone Marrow
• Peripheral Blood
• Cord Blood
 Gene Therapy
 Sickle cell Anemia
Terminology
Sickle cell disease: A group of disorders with abnormalities
caused by haemoglobin S
 Sickle cell trait/sickle cell carrier: A person with only one
sickle cell gene is asymptomatic and said to be a carrier.
 Sickle cell anemia: A person with two sickle cell genes (Hb
SS) and manifest as sickle cell anemia.
 Sickle cell syndromes: When a person is homozygous to
HbS or heterozygous for HbS but with any one of the
haemoglobinopathies like Thalassemia,HbC etc.
 Genetics of sickle cell anemia

• The gene related to sickle cell anemia is the hemoglobin

gene (HBB).
• The HBB protein is 146 amino acids long.
The HBB gene is found on chromosome 11.
• Single base pair change thymine for adenine at the 6th
position of the betaglobin chains
• Valine is substituted for glutamic acid on the beta
polyeptide chain.
Sickle cell is an autosomal recessive disease.
Therefore, the child can only get Sickle cell if
both parents are carriers, They have a 25%
chance of getting it if both are carriers
Sickle Cell Anemia: HbSS
• This results when both copies
of the hemoglobin beta gene
have an S mutation.
• All of this person’s beta
subunits are replaced by beta
S.
PATHOGENESIS
Normal Hb containing cells are
smooth, round, bi concave, flexible
easily deformable , nonsticky (Bag of
jelly)and can move through the
vessels easily .
 Half life of RBC with Normal Hb is
120 days.
 Pathogenesis
• The properties of HbS results in the
clinical manifestations of sickle cell
disease.
• Doxygenation of Haemoglobin S results
in polymerisation of HbS
• Distortion of RBC shape and form into
shape of sickle or C .
• Sickle cells are rigid, decreases
deformability of RBC and become sticky
and form clusters.
• Clusters cause blockage and stops
movement of normal oxygen carrying
blood also.
• Ishaemia of affected tissues.
• Causes painful and damaging
complications of sickle cell anemia.
• The spleen is an organ that filter blood of infection and due
to their shape and stiffness the sickle cells get struck in this
filter and die.
• The half life of RBC with HbS is only 15 days.
• The spleen also suffer damage due to the vaso-occlussive
phenomenon.
• The function of spleen is deranged and the children are at
risk for infections.
 Complications
• Vaso-occlussive crisis.
• Sequestration crisis.
• Haemolytic crisis.
• Aplastic crisis.
• Infections.
• Complications due to treatment.
VASO-OCCLUSIVE CRISIS
 Stroke, Focal seizures, Aphasia etc.
 Acute chest syndrome.
 Avascular necrosis of femoral / humeral head
 Corpus cavernosum - Priapism – Erectile impotence
 Dactylitis / Hand and foot syndrome: Painful swelling of the
small bones of hands and feet.
 Infarction of renal medulla- hyposthenuria, ATN
 Ocular- Orbital infarcts, Proliferative retinopathy.
 Skin ulcers- on lower limbs.
 Splenic infarcts- Auto splenectomy.
 Acute pain abdomen
 SEQUESTRATION CRISIS

• Common < 6years of age

• Often preceded by infection
• In response to fever spleen enlarges suddenly and traps
blood cells
• Hb fall dramatically, Retic count normal, Thrombocytopeia
present
• Hypovolemic shock if severe sequestration.
 INFECTION
• Due to underlying functional asplenia ?defective immunity
against encapsulated organisms (eg, Haemophilus
influenzae, Streptococcus pneumoniae)
• Also:  IgM levels, impaired opsonization, and sluggish
alternative complement pathway activation.
• Increased susceptibility to other common infectious
agents (Mycoplasma pneumoniae, Salmonella
typhimurium, Staphylococcus aureus, and Escherichia coli)
 APLASTIC CRISIS
• Due to parvo virus B 19 Infection/ folate deficiency
• Results in rapid onset of severe anemia.
• Due to supression of erythroid production in marrow.
• Retic count is low.
• Platelet , WBC normal.
 Haemolytic crisis
• Hyperemia, Dehydration ,Hypoxia Increases haemolysis.
 Complications due to haemolysis
• Chole lithiasis
• Cholecystitis.
• Obstructive jaundice
• Unconjugated hyperbilirubinemia
 Complications due to treatment
• Iron overload,
• Hepatitis B , C infection
An x-ray of a hand swollen from dactylitis
 Imaging Studies

• Specific to symptoms
• CXR if respiratory symptoms (may be nl in acute chest)
• Bone Xray if localized bone tenderness
• (Note: Bone scans can aid in early differentiation of bone infarction
and osteomyelitis)
• Abd US or CT if abd pain to r/o cholecystitis or acute
abdomen, also useful to assess liver and spleen size.
• Head CT/MRI in neurological symptoms
 MANAEMENT
There is no known cure for sickle cell anemia.

The four main treatment options are:

Blood Transfusions
Drug Treatment
Blood and Marrow Stem Cell Transplantation
Gene Therapy

These main treatment options for the painful crisis involves heavy
reliance on painkilling drugs and oral and intravenous fluids
whose main functions are to reduce pain and prevent
complications.
 Indications for blood transfusion
• Symptomatic episodes of acute anemia.
• Severe symptomatic chronic anemia.
• Prevention of recurrent stroke.
• Acute chest syndrome with hypoxia.
• Surgery with general anesthesia, Eye surgery.
• Refractory leg ulcers.
• Refractory and protracted pain symptoms.
• Acute severe priopism
Hydroxyurea
• Selectively kills cells in BM --> Stimulate erythroblasts that make Hb
F  s polymerization of HbS
• Use in severe complications
• Dosing:
• Start 500 mg/day and to 1,000mg/day after 6-8 weeks
• Maintenance: 1000-2000mg/day
• Monitoring:
• CBC q4-6 weeks (decreases WBC and PLTs)
• Monitor for a decline in granulocyte or platelet counts.
• MCV ~ marker of HbF levels
• Stop if a patient does not respond after several months of
hydroxyurea therapy
• Long term side-effects are unknown
 Pain Crisis
• HYDRATION
• PAIN CONTROL
• Opiates
• Ketorolac
• R/O INFECTION
• Oxygen (only if hypoxic)
• Tranfusions
• Newer approaches:
• Anticoagulation
• Epidural anesthesia
• Steroids
• Poloxamer 188 : an artificial nonionic surfactant that reduces sickle
erythrocyte adherence to the endothelium
Chest Crisis
• Presence of the following signs and symptoms in a patient with
sickle cell disease:
• Chest pain
• Temperature >38.5ºC
• Tachypnea, wheezing, or cough
• Etiology: Unclear
• Infarction, infection, fat embolism
• Diagnosis: No lab/imaging study can differentiate from other
pulmonary causes
• Management: IVF, pain control with opiates,
• Blood transfusion if hypoxic
• Exchange transfusion if worsening infiltrates
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