Haemolytic anemia

1. Haemolytic anaemia
• BY- PRATYASHA PARIPURNA
• GROUP 08
• 4TH SEMESTER

2. Hemolytic anemia
• Red blood cells have the important mission of carrying oxygen
from your lungs to your heart and throughout your entire
body. Your bone marrow is responsible for making these red
blood cells.
• When destruction of red blood cells outpaces your bone
marrow’s production of these cells, hemolytic anemia occurs.
• Hemolytic anemia can be extrinsic or intrinsic.

3. Pathophysiology
• Hemolytic anemia is the destruction of RBCs.
Normally, red blood cells have a lifespan of 120
days. This process can be something chronic that
has occurred over time or acute and life-
threatening. It can be further subdivided as to
where the hemolysis is taking place -
intravascularly or extravascularly.
• When a red blood cell is unable to change shape
as it passes through the spleen, it will become
sequestered and phagocytosis will occur. This is
seen in hemoglobinopathies such as sickle cell
disease.

4. Extrinsic hemolytic
• Extrinsic hemolytic anemia develops by several
methods, such as when the spleen traps and
destroys healthy red blood cells, or an
autoimmune reaction occurs. It can also come
from red blood cell destruction due to:
• infection
• tumors
• autoimmune disorders
• medication side effects
• leukemia
• lymphoma

5. Intrinsic hemolytic
• Intrinsic hemolytic anemia develops when the
red blood cells produced by your body don’t
function properly. This condition is often
inherited, such as in people with sickle cell
anemia or thalassemia, who have abnormal
hemoglobin.
• Other times, an inherited metabolic abnormality
can lead to this condition, such as in people with
G6PD deficiency, or red blood cell membrane
instability, such as hereditary spherocytosis.
• Anyone of any age can develop hemolytic
anemia.

6. Causes of hemolytic anemia
• enlarged spleen
• infectious hepatitis
• Epstein-Barr virus
• typhoid fever
• E. coli toxin
• leukemia
• lymphoma
• tumors
• systemic lupus erythematosus (SLE), an autoimmune disorder
• Wiskott-Aldrich syndrome, an autoimmune disorder

7. What are the symptoms of hemolytic anaemia?
• paleness of the skin
• fatigue
• fever
• confusion
• light-headedness
• dizziness
• weakness or inability to do physical activity
• dark urine
• yellowing of the skin and the whites of the eyes (jaundice)
• heart murmur

8. Medications
hemolytic anemia is the result of taking certain medications. This is known as drug-induced hemolytic
anemia. Some examples of medications that could cause the condition are:
• acetaminophen (Tylenol)
• antibiotics, such as cephalexin, ceftriaxone, penicillin, ampicillin, or methicillin
• chlorpromazine (Thorazine)
• ibuprofen (Advil, Motrin IB)
• interferon alpha
• procainamide
• quinidine
• rifampin (Rifadin)

9. Treatment
• Treatments for hemolytic anemia include
• blood transfusions,
• medicines,
• plasmapheresis
• surgery,
• blood and
• marrow stem cell transplants,
• and lifestyle changes.
• People who have mild hemolytic anemia may
not need treatment, as long as the condition
doesn't worsen.

10. Diagnosing hemolytic
anemia
• These blood tests help to diagnose hemolytic
anemia by measuring your:
• Bilirubin. This test measures the level of red
blood cell hemoglobin that your liver has broken
down and processed.
• Hemoglobin. This test indirectly reflects the
amount of red blood cells you have circulating in
your blood (by measuring the oxygen-carrying
protein within your red blood cells)
• Liver function. This test measures the levels of
proteins, liver enzymes, and bilirubin in your
blood.
• Reticulocyte count. This test measures how
many immature red blood cells, which over time
mature into red blood cells, that your body is
producing

11. Hemolytic anemia in
newborns
• Hemolytic disease of the newborn is a condition that
occurs when a mother and baby have incompatible blood
types, usually because of Rh incompatibility. Another
name for this condition is erythroblastosis fetalis.
• In addition to the ABO blood types (A, B, AB, and O)
discussed earlier, Rh factor also figures in a person’s
specific blood type: A person can be either negative or
positive for Rh factor. Some examples include A positive,
A negative, AB negative, and O positive.
• If a mother has a negative Rh blood type and her baby’s
father has a positive one, there’s a chance hemolytic
disease of the newborn can occur if the baby’s red blood
cells are then positive for Rh factor.
• The effects of this are just like red blood cell transfusion
reactions where there is an ABO mismatch. The mother’s
body sees the baby’s blood type as “foreign” and could
potentially attack the baby.

12. Hemolytic
anemia in
children
The causes are similar to those found in adults and
include:
infections
autoimmune diseases
cancers
medications
a rare syndrome known as Evans syndrome

13. How is hemolytic anemia
treated?
• Treatment options for hemolytic anemia differ
depending on the reason for anemia, severity of
the condition, your age, your health, and your
tolerance to certain medications.
• Treatment options for hemolytic anemia may
include:
• red blood cell transfusion
• IVIG
• immunosuppressantsTrusted Source, such as a
corticosteroid
• surgery

14. • Red blood cell transfusion
• A red blood cell transfusion is given to quickly increase your red blood cell count and to replace
destroyed red blood cells with new ones.
• IVIG
• You may be given immunoglobulin intravenously in the hospital to blunt the body’s immune system if
an immune process is leading to hemolytic anemia.

15. • Corticosteroids
• In the case of an extrinsic form of hemolytic anemia of autoimmune origin, you may be prescribed
corticosteroids. They can reduce your immune system activity to help prevent red blood cells from
being destroyed. Other immunosuppressants may be used to achieve the same goal.
• Surgery
• In severe cases, your spleen may need to be removed. The spleen is where red blood cells are
destroyed. Removing the spleen can reduce how fast red blood cells are destroyed. This is usually
used as an option in cases of immune hemolysis that don’t respond to corticosteroids or other
immunosuppressants.

16. •Splenomegaly: In the case of extravascular haemolyses, the spleen can be enlarged. The
spleen is the site of destruction of the red blood cells.
• The spleen tip is measured in centimetres below the left costal margin. Massive splenomegaly can be
readily palpated as a firm left-sided abdominal mass, though this is a rare presentation in the case of
hemolytic anemia.
• Massive splenomegaly is more often seen in conditions in which the bone marrow is replaced by fibrous
tissue like myelofibrosis, during which the compensatory mechanism is extramedullary haematopoiesis in
the spleen. In one population, 81% of patients with hemolytic anemia presented with splenomegaly.
•Hepatomegaly:Hepatomegaly, or liver enlargement, is a relatively uncommon
presentation of hemolytic anemia. In one population, 76% of patients with hemolytic anemia presented
with hepatomegaly. Hepatomegaly is measured in centimetres' below the right costal margin.

17. • Pallor: This occurs due to anemia and loss of oxygen-carrying ability of blood. Pallor can occur in
the skin or mucous membrane . In one population, 89% of patients with hemolytic anemia presented
with pallor, and this is the most common physical exam finding in hemolytic anemia.
• Fever:This can be a rare manifestation of hemolytic anemia. Fever is not specific for hemolysis. In
one population, 38% of patients with hemolytic anemia presented with fever.

18. Extravascular haemolysis
Physiological red cell
destruction occurs in the fixed
reticulo- endothelial cells in
the liver or spleen, so avoiding
free haemoglobin in the
plasma.
In most haemolytic states,
haemolysis is predominantly
extravascular
The compensatory erythroid
hyperplasia may give rise to
folate deficiency, when the
blood findings will be
complicated by the presence
of megaloblastosis.
Measurement of red cell folate
is unreliable in the presence of
haemolysis and serum folate
will be elevated.
Patients' red cells can be
labelled with51chromium;
when reinjected, they can be
used to determine red cell
survival, or when combined
with surface counting may
indicate whether the liver or
the spleen is the main source
of red cell destruction.

19. Intravascular haemolysis
When rapid red cell destruction occurs, free haemoglobin is released into the plasma. Free
haemoglobin is toxic to cells and the body has evolved binding proteins to minimise this risk.
Haptoglobin is an α2-globulin produced by the liver which binds free haemoglobin, resulting in a fall in
levels of haptoglobin.
Once haptoglobins are saturated, free haemoglobin is oxidised to form methaemoglobin which binds
to albumin, in turn forming methaemalbumin which can be detected by the Schumm's test.
Methaemoglobin is degraded and any free haem is bound to a second binding protein termed
haemopexin.
.

20. Classification of hemolytic anemia
2 types-:
acquired inherted

21. Causes of
inherited
Hemolytic
anemia:
Enzymopathies:
G6PD deficiency.
Pyruvate kinase deficiency.
Membrane defect:
Hereditary spherocytosis.
Hereditary Ovalocytosis.
Haemoglobinopathies :
Thalassaemias : quantitative Hbpathies.
Qualitative Hbpathies : Hb S, C, D, E etc.

22. 1-Enzymopathies
• Glucose 6 Phosphate Dehydrogenase Deficiency
Definition of G6PD Deficiency
• Sex-linked inherited disorder characterized
usually by acute hemolytic episodes following
exposure to oxidant stress (infection, drugs or
fava beans), due to deficiency of RBC enzyme
G6PD

23. Role of G6pd
enzyme in rbc
metabolism
• The red cells need energy, to maintain the cationic pump
(responsible for keeping K in and Na and Ca out and
hemoglobin in reduced thus functional of cells) form.
• Main source of energy is glucose, which is used to generate
ATP (essential for cationic pump) and NADPH (essential for
keeping Hb in reduced state) through the glycolytic pathway.
• While, NADPH (also important in generation of reduced
glutathione important in handling oxidants, and this
preventing RBC damage) is generated via the hexose
monophosphate shunt for which the action of enzyme G6PD
is initial step.
• In general, defects in the hexose monophosphate shunt result
in periodic haemolysis induced by oxidative stress, whilst
those in the Embden-Meyerhof pathway result in shortened
red cell survival and chronic haemolysis .

24. Pyruvate kinase
Deficiency :
• -This enzyme is an important key enzyme along
the glycolytic pathway, and is essential for ATP
generation.
• -Its deficiency is inherited as autosomal
recessive.
• -Associate with life long hemolytic anemia, with
pallor, jaundice and splenomegaly.
• -Normochromic anaemia with increased retics
and diagnosed by RBC Pyruvate kinase enzyme
assay.

25. Hereditary spherocytosis
• This is usually inherited as an autosomal
dominant condition, although 25% of cases have
no family history and represent new mutations.
• The incidence is approximately 1 : 5000 in
developed countries.
• The most common abnormalitiesare
deficiencies of beta spectrin or ankyrin.

26. Acquired
Haemolytic anemias
• 1-Immune
-warm antibody
-cold antibody
• 2-Non immune
-Microangiopathic hemolysis ( Disseminated intravascular
coagulation ,Thrombotic thrombocytopenic purpura ,
Preeclampsia, eclampsia, HELLP , Drugs (mitomycin,
cyclosporine) , Valvular hemolysis)
-Infection
- Paroxysmal nocturnal hemoglobinuria

27. Immune HA
• 1. Immune HA:
• Hemolytic anemia due to antibodies directed
• against red cells. These antibodies maybe
“produced by the patient Autoimmun against his
own red cells”.
• Or these Antibodies maybe Alloantibodies
introduced to the patient’s circulation and acting
against his red cells;
• or these maybe produced by patient and
directed against alloantibodies red cells
antigens introduced
• to the patient by blood transfusion or drugs.

28. WARM AIHA
• This AIHA in which the auto-antibody best reacts
with red cells at 37C,
• is usually class and usually react against Rhesus
an IgG antigens, and is usually associated with
extravascular hemolysis and account for , 80% of
cases

29. Paroxysmal Nocturnal
Hemoglobinuria :
• This rare acquired non-malignant clonal
expansion of haematopoietic stem cells
deficient in GPI-anchor protein results in
intravascular haemolysis and anaemia because
of increased sensitivity of red cells to lysis by
complement.
• Normal erythrocytes are protected from
complement- mediated cell lysis by the
presence of membrane proteins, including delay
accelerating factor (DAF) and membrane
inhibitor of reactive lysis (MIRL). Traditional tests
for PNH were functional assays based on the
increased susceptibility of erythrocytes to lysis
by acidic serum (Ham test) or hypotonic
medium (sucrose lysis test).

30. Prognosis
• The prognosis for patients with hemolytic
anemia depends on the underlying cause.
• Overall, mortality rates are low in hemolytic
anemias. However, the risk is greater in older
patients and patients with cardiovascular
impairment.
• Morbidity depends on the etiology of the
hemolysis and the underlying disorder, such as
sickle cell anemia or malaria.

31. Management
• Blood transfusion during the episode.
• Spontaneous recovery .
• No Cure.
• Patient should avoid Fava beans , certain drugs,
e.g. certain antimalarials(primaquine, quinine,
chloroquine, pyrimethamine ), sulphonamides,
septrin, aspirin, salazopyrine, Nalidixic acid,
Nitrofurantoin ciprofloxacin quinidine,
probenecid, vitamin K, dapsone.

32. Epidemiology
• Hemolytic anemia represents approximately 5% of all anemias. Acute
AIHA is relatively rare, with an incidence of one to three cases per
100,000 population per year. [
• Hemolytic anemias are not specific to any race. However, sickle cell
disorders are found primarily in Africans, African Americans, some
Arabic peoples, and Aborigines in southern India.
• Several variants of G6PD deficiency exist. The A(-) variant is found in
West Africans and African Americans. Approximately 10% of African
Americans carry at least 1 copy of the gene for this variant. The
Mediterranean variant occurs in individuals of Mediterranean
descent and in some Asians.
• Most cases of hemolytic anemia are not sex specific. However, AIHA
is slightly more likely to occur in females than in males. G6PD
deficiency is an X-linked recessive disorder. Therefore, males are
usually affected, and females are carriers.
• Although hemolytic anemia can occur in persons of any age,
hereditary disorders are usually evident early in life. AIHA is more
likely to occur in middle-aged and older individuals.

33. END