ACQUIRED HEMOLYTIC ANEMIA

1. Acquired Hemolytic Anemias
Dr. Jeena Raj
KAP Viswanatham Medical College

2. Immune Hemolytic Anemias
 Antibody mediated hemolysis is an important
cause of acquired hemolytic anemia.
 Autoantibodies or alloantibodies
 Characterized by a positive direct Coomb’s test.
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6. Autoimmune Hemolytic
Anemias

7.  Autoimmune hemolytic anemia (AIHA)-->
a positive Coombs test or DAT--> detects
antibody on the RBC surface.
 AIHA is classified into warm and cold
types.
 Depending on whether the antibody reacts
more strongly with red blood cells at
37°C or at 4°C and whether IgG (warm)
or IgM (cold) autoantibody predominates.
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8.  Hemolysis--> extravascular in AIHA,
although complement-mediated
intravascular hemolysis may sometimes
occur in either type.
 The degree of anemia--> rate and
acuteness of the destruction and the
capacity of the bone marrow to
compensate.
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9. AIHA may occur:-
1) Primary
2) Secondary: SLE and rheumatoid arthritis),
malignancy (lymphoma, thymoma and
chronic lymphocytic leukemia) or drug
exposure.
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10.  Warm autoimmune hemolytic anemia:
 The autoantibodies are polyclonal & IgG in
type.
 They react best at 37oC.
 Red cells coated with IgG are taken up by
macrophages especially in the spleen
which have receptors for the Fc fragment.
 Part of the coated membrane is lost so
the cell becomes progressively more
spherical to maintain its volume & is
ultimately prematurely destroyed
predominantly in the spleen.
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11.  It is classified as:-
 Idiopathic
 Secondary to autoimmune disoders,
lymphoma, CLL, drugs
 An underlying or associated disorder can
be identified in 50–70% of cases.
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12.  Clinical features:
 Can occur at any age in both sexes &
presents as a hemolytic anemia of variable
severity.
 The spleen is often enlarged.
 Presentation is variable and depends on
the speed with which anemia develops,
the capacity of the bone marrow to
compensate and the effects of any
associated disease.
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13.  Most commonly, the onset is insidious,
with the gradual awareness of symptoms
of anemia.
 Occasionally, the onset is acute, with
rapidly developing anemia and, in older
patients, the risk of heart failure.
 Rarely, severe cases can occur with
fulminating hemolysis, resulting in life-
threatening anemia.
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14.  Laboratory findings:
 Features of hemolytic anemia: anemia,
reticulocytosis, jaundice.
 Direct Coomb’s test is positive.
 Blood film --> Spherocytes, polychromasia
& nucleated red cells.
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16. Cold autoimmune hemolytic
anemia:
 The cold autoantibody attaches to red cells
mainly in the peripheral circulation where blood
temperature is cooled.
 The antibody is usually IgM & binds to red cells
best at 4oC.
 Agglutination of red cells by the antibody causes
acrocyanosis.
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17. Etiology: types of cold autoimmune
hemolytic anemia are:
 Idiopathic (cold hemagglutinin disease):
monoclonal antibody.
 Secondary to lymphoproliferative disease:
monoclonal antibody.
 Secondary to infection (Mycoplasma
pneumoniae or infectious mononucleosis):
polyclonal antibody.
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18.  Clinical features:
 Chronic hemolytic anemia aggravated by
cold & often associated with intravascular
hemolysis.
 Acrocyanosis (purplish skin discoloration)
at the tip of the nose, ears, fingers & toes
 Mild jaundice & splenomegaly may be
present.
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20. Laboratory findings:
 Features of hemolytic anemia.
 Direct Coomb’s test is positive.
 Blood film shows red cell
autoagglutination.
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22. Alloimmune Hemolytic
Anemias

23. Hemolytic disease of the
newborn:
 This results from passage of IgG antibodies from
the maternal circulation across the placenta into
fetal circulation.
 React with fetal red cells & mediate destruction by
fetal reticuloendothelial system.
 Antibodies are commonly directed against Rh and
ABO antigens.
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25. • Rh D negative woman pregnant with an Rh D
positive fetus--> fetal red cells cross into the
maternal circulation (usually at delivery) they will
sensitize the mother to produce anti-D
antibodies.
• The mother could also be sensitized by a
previous miscarriage, amniocentesis or other
trauma to the placenta or by blood transfusion.
• Anti-D antibodies will cross the placenta to the
fetus during the next pregnancy with a D-positive
fetus, coat fetal red cells & result in their
destruction causing anemia & jaundice.
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26.  Clinical features:
 The severity is variable.
 In severe disease: intrauterine death
results from hydrops fetalis.
 In moderate disease; the baby is born with
severe anemia, jaundice, edema &
hepatosplenomegaly. Kernicterus may
result.
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27. Laboratory findings:
 Cord blood: there is variable anemia,
reticulocytosis & jaundice.
 The baby is Rh positive. Direct Coomb’s
test is positive.
 In moderate & severe cases many
erythroblasts are seen in the blood film
(erythroblastosis fetalis).
 The mother is Rh D negative & has a high
level of anti-D. 27

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29. Drug-induced immune hemolytic
anemia
 Antibody-induced hemolytic anemia
caused by drugs is rare but in some cases
may be acute, severe and even life-
threatening.
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30.  Four main mechanisms:
1) drug adsorption
2) immune complex
3) membrane modification mechanisms that
lead to antibodies reacting with novel
epitopes
4) true autoantibody-induced hemolytic
anemia.
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31.  The diagnosis of drug-induced immune
hemolytic anemia should be made in three
stages:
1) Diagnosis of a DAT- positive hemolytic
anemia;
2) Careful drug history;
3) Serological demonstration of drug-specific
antibody, which interacts with red cells.
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32. Non Immune Hemolytic
Anemias

33. Red cell fragmentation
syndromes:
These arise through physical damage to red cells due
to:
 Cardiac hemolysis: prosthetic heart valves, grafts,
perivalvular leaks
 AV malformations
 Microangiopathic: TTP/HUS, Malignant disease
Vasculitis, Pre-eclampsia, HELLP, Renal vascular
disorders, DIC
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34.  Lab findings:
 Features of intravascular hemolysis
 Blood film shows many red cell
fragments.
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36. Infections causing hemolytic
anemia
 Falciparum malaria
 Babesiosis
 Bartonella
 Meningococcal sepsis
 Pneumococcal sepsis
 Atypical mycobacterial infections
 HIV
 Viruses
 Clostridium perfringens
 Snake, spider bites
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37. Chemical and physical
agents that may cause hemolytic anemia
 Drugs
 Industrial/domestic substances
 Burns
 Drowning
 Lead poisoning
 Copper (Wilson disease)
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38. Acquired membrane disorders
 Liver disease: Some degree of shortening
of red cell survival occurs in most cases of
acute hepatitis, cirrhosis and Gilbert
disease.
 Paroxysmal nocturnal hemoglobinuria
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39. Aplastic Anemia
 Aplastic anemia is a heterogeneous
disorder characterized by pancytopenia
and a hypocellular marrow without any
apparent underlying neoplastic process.
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40. Etiology:
 Primary: Congenital e.g. Fanconi’s anemia
Idiopathic
 Secondary:-
 Ionizing radiation
 Chemicals: benzene & other organic solvents,
insecticides, hair dyes
 Drugs: Which regularly cause marrow
depression e.g. busulphan,
cyclophosphamide.
Which rarely cause marrow depression e.g.
chloramphenicol, sulphonamides.
 Infection: viral hepatitis (non-A non-B)
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41.  Pathogenesis:
 Substantial reduction in the number of stem cells
& a fault in the remaining stem cells or an
immune reaction against them.
 Unable to divide & differentiate sufficiently to
populate the bone marrow.
 A primary fault in the marrow microenvironment
has also been suggested but the success of
bone marrow transplantation shows this can
only be a rare cause since normal donor stem
cells are usually able to thrive in the recipient’s
marrow cavity.
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42.  Clinical features:
 The onset is at any age with a peak incidence around 30
years & a slight male predominance.
 Insidious or acute with symptoms & signs resulting from
anemia, neutropenia or thrombocytopenia.
 Infections, particularly of the mouth & throat, are
common. Generalized infections are frequently life
threatening.
 Bruising, bleeding gums, epistaxes & menorrhagia are
the most frequent hemorrhagic manifestations & the
usual presenting features.
 Symptoms of anemia.
 The lymph nodes, liver & spleen are not enlarged.
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43.  Laboratory findings:
 Anemia is normochromic normocytic or macrocytic.
The retic count is reduced.
 Leucopenia. There is selective neutropenia usually
but not always to below 1.5 x 109/L. The neutrophils
appear normal.
 Thrombocytopenia is always present & in severe
cases is less than 10x109/L.
 There are no abnormal cells in the peripheral blood.
 Bone marrow shows hypoplasia with loss of
hemopoietic tissue & replacement by fat.
 Bone marrow biopsy is essential & may show
patchy cellular areas in a hypocellular background.
The main cells present are lymphocytes & plasma
cells.
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47.  Differential diagnosis: other causes of
pancytopenia are:
 Bone marrow infiltration e.g. carcinoma,
lymphoma.
 Leukemia, MDS, myeloma.
 Hypersplenism.
 Megaloblastic anemia.
 Myelofibrosis.
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48. THANK YOU