L11._Hemolytic_Anaemia.pdf. .

Medical research

1. Hemolytic Anaemia

2. Introduction
Haemolytic anaemias are defined as those anaemias that
result from an increase in the rate of red cell
destruction.
Destruction of red blood cells (RBC) either in the blood vessels (
intravascular hemolysis) or in the bone marrow, lymph node or
spleen ( extravascular hemolysis).
.

3. In hemolytic anemia's, the red blood cells are destroyed
prematurely and removed from the circulation before
their normal lifespan of 120 days
The hallmark of these disorders is reduced life span of
the red cells rather than under production by the bone
marrow.

The cells are broken down at a faster rate than the bone
marrow can produce new cells.

4. Hemoglobin, the component of red blood cells that
carries oxygen, is released when these cells ( RBCs) are
destroyed.
Hemolytic anemia's are identified as the disorder that
brings about the premature destruction of RBCs and
these disorders can either be inherited or acquired.

5. Classification of hemolytic anaemia
1.Hereditary haemolytic anaemias are the result of ‘
intrinsic’ red cell defects.
2.Acquired haemolytic anaemias are usually the result of
an ‘ extracorpuscular ’ or ‘environmental’ change
.
Paroxysmal nocturnal haemoglobinuria (PNH) is the
exception because although it is an acquired disorder, the
PNH red cells have an intrinsic defect.

7. Clinical features
Anaemia
condition in which the number of red blood cells or the
amount of hemoglobin is below normal range of age and sex.

Symptoms of anaemia are fatigue, palor , fever, shortness of
breath, headache.

8. Clinical features
Jaundice
Jaundice appears as the yellowish color of the skin or
whites of the eyes.
When red blood cells die, they release hemoglobin into
the bloodstream.

The hemoglobin is then broken down into bilirubin,
which gives the skin and eyes a yellowish color. Bilirubin
also causes urine to be dark yellow or brown.

9. Clinical features
Pain in the Upper Abdomen
Gallstones or an enlarged spleen (splenomegaly) may
cause pain.
The spleen is an organ in the abdomen that helps fight
infection and filters out old or damaged blood cells.
In hemolytic anemia, the spleen may be enlarged, which can be painful.

10. Clinical features
Splenicpain
As a result of splenicinfarction and splenomegaly.
Leg Ulcers and Pain

11. Clinical features
A Severe Reaction to a Blood Transfusion
It can occur if the transfused blood is different from the
recipients blood type.

Signs and symptoms of a severe reaction to a transfusion include fever, chills, low blood pressure and shock.

12. Mechanisms of hemolysis:
Intravascular hemolysis
Extravascular hemeloysis

13. Intravascular hemolysis
Red blood cell destruction occurs within the vascular space.
Whichever mechanism dominates will depend on the
pathology involved.
Free haemoglobin is released which rapidly saturates plasma
haptoglobinsand the excess free haemoglobin is filtered by
the glomerulus.
If the rate of haemolysissaturates the renal tubular
reabsorptivecapacity, free haemoglobin enters urine and, as
iron is released, the renal tubules become loaded with
haemosiderin.

14. Methaemalbuminis also formed from the process of
intravascular haemolysis

15. Causes of Intravascular hemolysis
1.Mismatched blood transfusion (usually ABO)
2.G6PD deficiency with oxidant stress
3.Red cell fragmentation syndromes
4.Some autoimmune haemolytic anaemias
5.Some drug - and infection -induced haemolytic anaemias
6.Paroxysmal nocturnal haemoglobinuria
7.March haemoglobinuria
8.Unstable haemoglobin

17. Causes of intravascular hemolysis
Acute hemolytic transfusion reactions
Severe and extensive burns
Paroxysmal nocturnal hemoglobinuria
Severe microangiopathic hemolysis
Physical trauma
Bacterial infections and parasitic infections (sepsis)

18. Laboratory features of Intravascular
hemolysis
Haemoglobinaemia and haemoglobinuria;
Haemosiderinuria (iron storage protein in the spun
deposit of urine.
Methaemalbuminaemia.

19. Hereditary hemolytic anaemia

20. Hereditary sperocytosis
Spherocytosis, is an inherited disease that destroys red
blood cells. This destruction of the red blood cells causes
anemia
Autosomal dominant.
Homozygous gene defect incompatible with life
The most common hereditary haemolytic anaemia in
Caucasian populations.
Incidence = 200 –300 per million of the population
Spherical RBCs lacking the central pallor of the normal
biconcave discs

21. •Increasedrigidityofredcellsleadstotheirsequestration
bythespleen.
•Theshapeofanormalredbloodcellresemblesadisk.
Normalredbloodcellseasilychangeshapetomove
effectivelythroughthesmallbloodvessels
•Inspherocytosistheredbloodcellsareveryroundand
havedifficultychangingshapemakingmovement
throughthesmallbloodvesselsdifficult.

22. spherocytes

23. Pathogenesis
HS is usually caused by defects in the proteins involved in
the vertical interactions between the membrane skeleton
and the lipid bilayer of the red cell which results in loss
of membrane
Marrow produces red cells of normal biconcave shape
but these lose membrane and become increasingly
spherical.
Ultimately, the spherocytesare unable to pass through
the splenicmicrocirculation where they die prematurely.

24. Clinical features
Most patients have splenomegaly caused by chronic
extravascular hemolysis.
They may appear jaundiced, and up to 50% develop
cholelithiasis, with pigmented (bilirubin) gallstones.
Chronic hemolysis, transfusion is generally not required.

25. An exception is a sudden decline in hemoglobin and
reticulocytes, which heralds an aplasticcrisis (usually
caused by infection by parvovirus B19).
Anemia may also become more severe in so-called
hemolytic crisis, during which there is a transient
acceleration of the hemolysis

26. Diagnosis of HS usually is established from:
1.Family history
2.Blood film
3.Splenomegaly
Diagnosis

27. Anemia, reticulocytosis, and spherocytosison
peripheral blood smear examination provide
strong hints to suggest the diagnosis of HS
.
Diagnosis

28. The classic laboratory features of HS include:
-low Hb(anaemia),
-Reticulocytosis,
-increased mean corpuscular hemoglobin
concentration (MCHC),
-Spherocyteson the peripheral blood smear, -
hyperbilirubinemia,
-Abnormal results on the Osmotic fragility test .
Lab diagnosis

29. Treatment
Patients with HS can be managed effectively by
splenectomy, although spherocytesstill persist in the
circulation.
Splenectomy, however, renders patients more susceptible
to certain infections, particularly with Streptococcus spp.
Should not be performed unless clinically indicated
because of symptomatic anaemia, gallstones, leg ulcers
or growth retardation.
This is because of the risk of post-splenectomysepsis,
particularly in early childhood.

30. There is also evidence for late vascular complications.
Cholecystectomyshould be performed with
splenectomyif symptomatic gallstones are present.

31. Hereditary Elliptocytosis
Hereditary elliptocytosis(HE) is a heterogeneous group
of inherited disorders involving the erythrocyte
cytoskeleton.
Heterogeneous disorders with elliptical red cells.

32. Types of HE
Types:
Common HE with discoidalelliptocytes.
Silent carriers :decrease expression of alpha spectrin
Hereditary pyropoikilocytosis
SpherocyticHE.

33. Pathogenesis
HE features an abnormality of the cytoskeleton.
More commonly described variants of HE include defects in
self assembly of spectrin, spectrin–ankyrinbinding, protein
4.1 and glycophorinC.
Regardless of the underlying molecular abnormality, most
circulating red cells are elliptical or oval.
They still have an area of central pallor, since there is no loss
of the lipid bilayer(as seen in HS).
Most forms of HE are autosomal dominant.

35. Clinical features and diagnosis
HE usually manifests with only mild normocyticanemia.
Many patients are asymptomatic.
Blood smears show numerous elliptocyteswith only
minimal reticulocytosis.
Generally, less hemolysis and subsequent anemia are seen
than are seen with HS.
Occasional patients with more severe hemolysis may
require splenectomy.