HEMOLYTIC DESORDERS
Red Cell Turnover and Life Span
2.5 million red cells are removed from
the circulation every second.
BM produces 200 billion new red cells
(reticulocytes) each day. These cell
survived for 120 days before they are
removed by the RES ( BM, liver,
spleen).
• HEMOLYTIC ANAEMIA (HA)
Definition
HA is a decrease in the total number of
circulating
erythrocytes that is caused by the
premature
destruction or removal of red cells from the
circulation.
Anaemia will result only if the rate of RBC
destruction exceed the BM response (uncompensation).
Haemolytic anaemia cont.
Because of erythropoietic hyperplasia and •
anatomical extension of bone marrow, red cell
destruction may be increased several fold before
the patient become anaemic --- compensated
haemolytic anaemia.
The normal adult marrow, after full expansion, is •
able to produce red cells at 6-8 times the normal
rate.
Therefore HA may not be seen until the red cell •
lifespan is less than 30 days.
.
Hg g/dl
NORMAL
16.7
Total Hg (g)
RBC SURVIVAL (days )
&
degraded
( g/day)
800
Hg produced
120
6.7
COMPENSATED
HAEMOLYTIC
ANAEMIA
16.7
800
20
40
Classification of HA
The HA can be classified in several different •
ways:
1- Site of haemolysis:
Extravascular haemolytic disorders - •
macrophages of the RES
Intravascular haemolytic disorders- within the •
circulatory system
In many of the cases there is a combination of •
both extra and intravascular haemolysis.
Extravascular haemolysis
Red cell destruction •
usually occurs in the
cell of the RES.
Intravascular haemolysis
Destruction of red •
cells occur inside
the blood vessels.
Classification of HA
2- Site of defect:
Intrinsic defect (intracorpuscular)- •
structural or functional defect within the
red cell.
Extrinsic defect (extracorpuscular)- an •
abnormality in the red cell environment.
Classification of HA
3- 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.
Inherited & acquired HA
Acquired HA
Hereditary HA
Membrane defects e.g
Immune
•
-
Autoimmune eg AIHA
Alloimmune e.g Hemolytic
Disease of Newborn,
HaemolyticTransfusion
Reaction
hereditary spherocytosis
Metabolic defect e.g
•
G6PD deficiency. •
Haemoglobin defects e.g
sickle cell disease.
•
Red cell fragmentation syndromes
March haemoglobinaemia
Infections
Chemical and physical agents.
PNH
Clinical features
Pallor of the mucous membranes •
Mild fluctuating jaundice •
Splenomegaly •
Dark urine •
Pigmented gall stones. •
Ulcers around the ankle •
Aplastic crisis may complicate viral infections. •
Growth retardation •
Hypertrophic skeletal changes •
Leg ulcers in •
patients with severe
congenital
haemolytic
disorders. e.g sickle
cell anaemia
Skeletal changes in •
patients with b
thalassaemia.
Laboratory manifestation •
I.
signs of excessive RBC destruction:
1-Decrease RBC life span
2-Increase catabolism of heme.
indirect hyperbilirubinaemia.
increase rate of bilirubin production.
increase rate of urobilinogen production
• Laboratory manifestation cont.
3-increase LDH activity
4-Absence of serum haptoglobin.
5-Signs of intra-vascular hemolysis.
Hemoglobinaenemia.
Hemoglobinuria.
Haemosiderinuria.
Methemealbuminaemia.
Decrease
hemopexin
Decrease Hb level.
Intravascular haemolysis
Free Hb will be released from damaged red •
cells.
This free Hb will rapidly saturates plasma •
haptoglobins. The complex will be removed by
the liver.
The excess free Hb is filtered by the glomerulus, •
and free Hb will enter the urine, as iron is
released, the renal tubules become loaded with
haemosiderin.
Methaemalbumin and haemopexin are also •
found in the process of IV haemolysis.
The process of •
intravascular
haemolysis
Liberation of free Hb •
Filtered through the •
kidney
Appear in urine as •
haemoglobinuria
Haemoglobinuria
Notice the dark •
colour of urine
compared to the
normal colour in the
other container.
This is a sign of •
intravascular
haemolysis.
II. signs of accelerated erythropoiesis :
Blood
reticulocytosis (polychromasia in the blood film).
Macrosytosis.
Normoblastaemia .
Leukocytosis and thrombocytosis .
Bone marrow.
Erythroid hyperplasia.
Ferrokinetics:
increase plasma iron turnover.
increase erythrocyte iron turnover
III. Lab tests useful in the differential diagnosis •
:
1-Morphology (blood film findings): (spherocytes, elliptocytes,
acanthocytes, stomatocytes, target cells, fragmented RBCs,
Autoagglutination)
2-Direct coomb’s test
3-Osmotic fragility test
4-Auto-hemolysis test.
5-Hb-electorphoresis test.
6-Sickling test.
7-Ham’s test.
8-Screening test for G6PD deficiency
.
Reticulocytosis is a •
feature of increased
red cell production.
New methylene blue •
is used to stain the
reticulocytes
Fragmented cells, •
and bitten cells are
sings of damaged
cells occurring in
haemolysis
Approach to the diagnosis
of haemolytic anaemias.
Patient’s history
Good history is essential to provide guidance •
for the diagnosis of haemolytic disorders. The
following points should not be neglected:
Family history--- hereditary conditions, mode •
of inheritance.
Ethnic origin--- G6PD deficiency is most •
common in Mediterranean and Chinese
populations.
Past history--- NNJ may be indicative of •
congenital conditions as HS or G6PD
deficiency.
Triggering events--- history of drugs, •
infections
Differential diagnosis of hemolytic anaemia
Anaemia with increase reticulocyte count •
*Hemorrhage •
**Recovry from deficiency of iron,B12, folate. •
***Recovery from marrow failure. •
Anaemia with acholuric jaundice •
*ineffective erythropoiesis. •
**Loss of blood in body cavity & tissue. •
Marrow invasion •
myoglobinuria •