This document discusses various types of acquired hemolytic anemias, including immune and non-immune causes. It covers autoimmune hemolytic anemia, distinguishing between warm and cold types. It also discusses alloimmune hemolytic anemias like hemolytic disease of the newborn. Non-immune causes discussed include red cell fragmentation syndromes, infections, chemicals/physical agents, and acquired membrane disorders. Aplastic anemia is also summarized, covering etiology, pathogenesis, clinical features, and differential diagnosis.

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