Transcript Sickle cell anaemia

Course title: Hematology (1)
Course code: MLHE-201
Supervisor: Prof. Dr Magda Sultan
Date : 19/ 12 / 2013
Outcome :
The student will know :
-The types of hemolytic anemias
-The diagnosis of hemolytic anemias
-The types of hereditary hemolytic anemias.
-The diagnosis of hereditary hemolytic anemias
-The laboratory tests needed for diagnosis
1-Hemolytic anemia(HA)
• HA = decreased levels of red blood
cells in circulating blood (anemia)
because of their accelerated
destruction (hemolysis)
• A red blood cell survives 120 days
• The spleen (part of the reticulo-endothelial
system) is the main organ which removes old
and damaged RBCs from the circulation.
• Breakdown of RBCs can exceed the rate that
the body can make RBCs and so anemia can
develop.
HEMOLYTIC ANEMIA

Anemia of increased destruction





Normochromic, normocytic anemia
Shortened RBC survival
Reticulocytosis - Response to increased
RBC destruction
Increased indirect bilirubin
Increased LDH
Classification of hemolytic anemias

Causes of hemolytic anemias can be
either:
1 - hereditary (genetic )
2 - acquired.
Physiologic classification of
anemia
Hemolytic anemia

Hereditary
 Defects of hemoglobin
 Thalassaemia, Sickle cell anemia
 Defects of the red cell membrane
 Hereditary spherocytosis, Hereditary
elliptocytosis
 Defective red cell metabolism (enzymes)
 G6PD deficiency. P K deficiency

Acquired
 Immune mediated : Autoimmune,
isoimmune, drugs
 Microangiopathic: DIC, HUS
 Hypersplenism
 Miscellaneous: drugs, toxin, infection,
burn, chemical
Mechanisms of hemolysis:
- intravascular
- extravascular
Intravascular hemolysis :
Red cell destruction occurs in vascular space
e.g eclinical states associated with Intravascular hemol
acute hemolytic transfusion reactions
severe burns
physical trauma
bacterial infections
Intravascular hemolysis :
- laboratory signs of intravascular hemolysis:
tests for hemolysis and aditionally:
hemoglobinemia
methemalbuminemia
hemoglobinuria
hemosiderinuria
Extravascular hemolysis
:red cells
destruction occurs in reticuloendothelial system
e.g
scyrestem
- clinical states associated with extravascular hemolysis :
autoimmune hemolysis
delayed hemolytic transfusion reactions
hemoglobinopathies
hereditary spherocytosis
hypersplenism
hemolysis with liver disease
- laboratory signs of extravascular hemolysis:
tests for hemolysis
Signs of hemolytic anemia: Physical
•
•
•
•
Symptoms of anemia
Jaundice
Pallor
Splenomegaly / hepatosplenomegaly
Laboratory features (1)
*Morphology:
anemia
*Peripheral blood smear microscopy:
 **fragments of the red blood cells
("schistocytes") can be present
 **some red blood cells may appear smaller
and rounder than usual (spherocytes)
 **reticulocytes are present in elevated
numbers.
 Normoblasts can be present.
Bone marrow smear microscopy:
* Erytrhroid hyperplasia
* The level of unconjugated bilirubin in
the blood is elevated.
* The level of lactate dehydrogenase
(LDH) in the blood is elevated
Laboratory features (2)
*The
direct CoombꞋs test is positive, if hemolysis
is caused by an immune process.
*Increased excretion of urobilinogen in the
urine
*Increased stercobilinogen in the stool.
*Sometimes abnormal results of the osmotic
fragility test
Hereditary Hemolytic anemia

Defects of hemoglobin


Defects of the red cell membrane


Thalassaemia, Sickle cell anemia
Hereditary spherocytosis, Hereditary
elliptocytosis
Defective red cell metabolism

G6PD deficiency. P K deficiency
Haemoglobinopathy
.

The abnormalities of the gene may result from
substitution of single amino acid like sickle cell
anaemia or decrease synthesis of the whole
globin chain (thalassaemia)
Sickle cell anaemia

Substitution of glutamic acid by valine
The Hb is stable when oxygenated state
and become unstable and polymerized on
deoxygenated state
Sickle cell anaemia


Polymerization will lead to precipitation of Hb.
The cell become deformed
(sickle shape)
and very sticky leading to vascular occlusion and
small infarction to the affected areas.
Short life span of cells leading to chronic
anaemia,
The origin of the disease is a small
change in the protein hemoglobin
The change in cell structure arises from a change in
the structure of hemoglobin.
A single change in an amino acid causes hemoglobin
to aggregate.
Sickle cell anaemia
Diagnosis
Laboratory:
Hb 6-9 g/dl, high retics (5-15%), Normocytic
anemia , target or anisocytosis
Sickling test
Hb electrophoresis
Hb S 60-100 in SS
Parents sickle trait Hb AS
Hgb Electrophoresis

Amino acids in globin chains have
different charges

Separates hemoglobin according to
charge

90% Hgb S, 10% Hgb F,
small fraction of Hgb A2
Thalassaemia
Means defective synthesis of one or more of the
globin chains which form normal hemoglobin. In
very severe form this globin is totally absent. The
defect may be in alpha chain ( thalassaemia),
Beta chain ( thalassaemia) or Delta chain (
thalassaemia)
HEMOGLOBIN


NORMAL ADULT RBC CONSISTS OF 3
FORMS OF Hb:
- HbA - 2 α and 2 β globin chains
- HbA2 – 2 α and 2 δ globin chains
- HbF - 2 α and 2 γ globin chains
THALASSEMIAS α and β
Different forms of thalassemia




Alfa thalassemia
Beta thalasemia: major, minor (trait),
intermedia
Delta/Beta thalassemia
Hereditary persistentce of fetal
hemoglobin (HPFH)
Beta Thalassaemia
Defective  chain synthesis
Excess  chain Precipitation
cell membrane damage
Circulating Red cell
Bone marrow
Anaemia
Hemolytic
Erythropoietin increased
Ineffective erythropoiesis
blood transfusion
 Iron absorption
Bone marrow expansion
skeletal changes & hyper metabolism
Iron overload
Complication and death
Beta-Thalassemia major
laboratory features

Severe anemia
Blood film: anisopoikilocytosis, hypochromia,
target cells, basophylic stippling, reticulocytes
moderately increased and normoblasts .
Marrow: marked erythroid hyperplasia,
increased sideroblasts
Shortened red cell survival

Haemoglobin electrophoresis :




Fetal hemoglobin > 90%, HbA
absent, HbA2 low/normal/high
HEREDITARY
SPHEROCYTOSIS





Defective or absent spectrin molecule
Leads to loss of RBC membrane,
leading to spherocytosis
Decreased deformability of cell
Increased osmotic fragility
Extravascular hemolysis in spleen
Hereditary spherocytosis
(HS)
Laboratory features
- hemolytic anemia
- blood smear-microspherocytes
- abnormal osmotic fragility test, acidified
glycerol lysis time
- negative direct Coombs test
G6PD DEFICIENCY
Function of G6PD
Infections
Drugs
2 H2O
GSSG
H2O2
2 GSH
NADPH NADP
6-PG
G6P
G6PD
Hgb
Sulf-Hgb
Heinz bodies
Hemolysis
Glucose 6-Phosphate Dehydrogenase
Functions



Regenerates NADPH, allowing regeneration of
glutathione
Protects against oxidative stress
Lack of G6PD leads to hemolysis during
oxidative stress




Infection
Medications
Fava beans
Oxidative stress leads to Heinz body
formation,  extravascular hemolysis
G6PD DEFICIENCY



DIAGNOSIS :
QUANTITATIVE ASSAY
DETECTING LOW ENZYME
TREATMENT – SUPPORTIVE AND
PREVENTATIVE
Assignement :
Student name :‫الشيماء مصطفي عبد العاطي‬
Title:Sickle cell anaemia
Student name :‫اميره اسعد يوسف‬
Title : Haemoglobin electrophoresis .
Student name :‫اميره صالح مرشدي‬
Title :G6PD deficiency .
Student name :‫انجي عبد الموجود‬
Title : Spherocytic anaemia .
Student name : ‫بسمه مهدي رياض‬
Title :Laboratory tests of hemolytic anaemias .
Training questions :
What are the tests of hemolysis ?
 How to diagnose Sickle cell anaemia ?
 How to classify hemolytic anaemias ?



Reference book :
Essential Hematology .
Dacie .