Immune Hemolytic

Anemia's

 Dr Abdifatah Ahmed
 Supervisor: Prof Silva
 October 2022
 Outline
2

1. Introduction

2. Etiology, epidemiology and pathogenesis

3. Clinical features

4. Diagnosis

5. Treatment

6. References
03/09/23
 Introduction

 Autoimmune hemolytic anemia (AIHA) is a collection of

disorders characterized by the presence of autoantibodies
that bind to the patient's own erythrocytes, leading to
premature red cell destruction (hemolysis) and, when the
rate of hemolysis exceeds the ability of the bone marrow to
replace the destroyed red cells, leads to anemia and its
attendant signs and symptoms.
 Introduction

 The hallmark of this group of diseases is the positive result

of the direct antiglobulin (Coombs) test, which detects a
coating of immunoglobulin or components of complement
on the RBC surface.
 The most important immune hemolytic disorder in pediatric
practice is hemolytic disease of the newborn
(erythroblastosis fetalis)
 Introduction

 Various other immune hemolytic anemias are autoimmune

and may be idiopathic or related to various infections
Cont.

AUTOIMMUNE HEMOLYTIC
ANEMIAS ASSOCIATED WITH
“WARM” ANTIBODIES
 Etiology

 In the autoimmune hemolytic anemias, autoantibodies are

directed against RBC membrane antigens, but the
pathogenesis of antibody induction is uncertain.
 The autoantibody may be produced as an inappropriate
immune response to an RBC antigen or to another antigenic
epitope similar to an RBC antigen, known as molecular
mimicry.
 Etiology

 Alternatively, an infectious agent may alter the RBC

membrane so that it becomes “foreign” or antigenic to the
host. The antibodies usually react to epitopes (antigens) that
are “public” or common to all human RBCs, such as Rh
proteins.
 Etiology

 In most instances of warm antibody hemolysis, no

underlying cause can be found; this is the primary or
idiopathic type.
 If the autoimmune hemolysis is associated with an
underlying disease, such as a lymphoproliferative disorder,
SLE, Evans syndrome, or immunodeficiency, it is
secondary. In as many as 20% of cases of immune
hemolysis, drugs may be implicated
Cont.
 Clinical Manifestations

 Autoimmune hemolytic anemias may occur in either of 2

general clinical patterns.

 The first, an acute transient type lasting 3-6 mo and

occurring predominantly in children age 2-12 yr., accounts
for 70–80% of patients. It is frequently preceded by an
infection, usually respiratory.
 Clinical Manifestations

 Onset may be acute, with pallor, jaundice, fever, and

hemoglobinuria, or more gradual, with primarily fatigue and
pallor.

 The spleen is usually enlarged and is the primary site of

destruction of IgG-coated RBCs. Underlying systemic
disorders are unusual.
 Clinical Manifestations

 A consistent response to glucocorticoid therapy, a low

mortality rate, and full recovery are characteristic of the
acute form.

 The other clinical pattern involves a prolonged chronic

course, which is more frequent in infants and in children
>12 yr old.
 Clinical Manifestations

 Hemolysis may continue for many months or years

Abnormalities involving other blood elements are common,
and the response to glucocorticoids is variable and
inconsistent.
 Laboratory Findings

 In many cases, anemia is profound with hemoglobin levels

<6 g/dL.
 Considerable spherocytosis, polychromasia (reflecting the
reticulocyte response) are present.
 More than 50% of the circulating RBCs may be
reticulocytes, and nucleated RBCs usually are present.
 Laboratory Findings

 In some cases, a low reticulocyte count may be found,

particularly early in the episode.
 Leukocytosis is common.
 The platelet count is usually normal, but concomitant
immune thrombocytopenic purpura sometimes occurs
(Evans syndrome).
 Laboratory Findings

 Results of the direct antiglobulin test (Coombs test) are

strongly positive, and free antibody can sometimes be
demonstrated in the serum (indirect Coombs test).
 These antibodies are active at 35-40°C (95-104°F) (“warm”
antibodies) and most often belong to the immunoglobulin G
(IgG) class.
 They do not require complement for activity.
 Laboratory
Cont. Findings

 In warm antibody hemolytic anemia, the direct Coombs test

may detect IgG alone, both IgG and complement fragments,
or solely complement fragments if the level of RBC-bound
IgG is below the detection limit of the anti-IgG Coombs
reagent.
 Treatment

 Transfusions may provide only transient benefit but may be

lifesaving in cases of severe anemia until the effects of other
treatments are observed. All tested units for transfusion are
serologically incompatible.
 It is important to identify the patient’s ABO blood group to
avoid a hemolytic transfusion reaction mediated by anti-A
or anti-B.
 Treatment

 The blood bank should also test for the presence of an

underlying alloantibody, which could cause rapid hemolysis
of transfused red cells.
 Patients with mild disease and compensated hemolysis may
not require treatment. If the hemolysis is severe and results
in significant anemia or symptoms, treatment with
glucocorticoids is initiated.
 Treatment

 Prednisone or its equivalent is administered at a dose of 2

mg/kg/24 hr. In some patients with severe hemolysis, doses
of prednisone of up to 6 mg/kg/24 hr may be required to
reduce the rate of hemolysis.
 Treatment should be continued until the rate of hemolysis
decreases, with the dose then gradually reduced. If relapse
occurs, resumption of the full dosage may be necessary.
 Treatment

 When hemolytic anemia remains severe despite

glucocorticoid therapy, or if very large doses are necessary
to maintain a reasonable Hb level, intravenous (IV)
immunoglobulin may be tried.
 Rituximab, a monoclonal antibody that targets B
lymphocytes, the source of antibody production, is useful in
chronic cases refractory to conventional therapy.
 Treatment

 Plasmapheresis has been used in refractory cases but

generally is not helpful.

 Splenectomy may be beneficial but is complicated by a

heightened risk of infection with encapsulated organisms,
particularly in patients <6 yr old.
 Course and Prognosis

 Acute idiopathic autoimmune hemolytic disease in

childhood varies in severity but is self-limited; death from
untreatable anemia is rare.
 Approximately 30% of patients have chronic hemolysis,
often associated with an underlying disease, such as SLE,
immunodeficiency or lymphoma.
 Mortality in chronic cases depends on the primary disorder.
Cont.

AUTOIMMUNE HEMOLYTIC
ANEMIAS ASSOCIATED WITH
“COLD” ANTIBODIES
 Introduction

 “Cold” antibodies agglutinate RBCs at temperatures <37°C

(98.6°F).
 They are primarily of the IgM class and require complement
for hemolytic activity.
 The highest temperature at which RBC agglutination occurs
is called the thermal amplitude.
 Introduction

 A higher thermal amplitude antibody—that is, one that can

bind to RBCs at temperatures achievable in the body—
results in hemolysis with exposure to a cold environment.
 High antibody titers are associated with high thermal
amplitude.
 Cold Agglutinin Disease

 Cold antibodies usually have specificity for the

oligosaccharide antigens of the I/i system.
 They may occur in primary or idiopathic cold agglutinin
disease, secondary to infections such as those from
Mycoplasma pneumoniae and Epstein-Barr virus, or
secondary to lymphoproliferative disorders.
 Cold Agglutinin Disease

 When very high titers of cold antibodies are present and

active near body temperature, severe intravascular hemolysis
with hemoglobinemia and hemoglobinuria may occur and
may be heightened on a patient’s exposure to cold (external
temperature or ingested foods).
 Each IgM molecule has the potential to activate a C1
molecule, so that large amounts of complement are found on
the RBCs in cold agglutinin disease.
 Cold Agglutinin Disease

 These sensitized RBCs may undergo intravascular

complement-mediated lysis or may be destroyed in the liver
and spleen.
 Only complement, not IgM, is detected on RBCs because
the IgM is removed during the washing steps of the direct
antiglobulin (Coombs) test.
 Cold Agglutinin Disease

 Cold agglutinin disease is less common in children than in

adults and more frequently results in an acute, self-limited
episode of hemolysis.
 RBC transfusion is indicated based on symptoms and
severity of anemia.
 Glucocorticoids are much less effective in cold agglutinin
disease than in hemolytic disease with warm antibodies.
 Cold Agglutinin Disease

 Patients should avoid exposure to cold and should be treated

for any underlying disease.
 In the uncommon patient with severe hemolytic disease,
immunosuppression and plasmapheresis can be used.
 Successful treatment of cold agglutinin disease has been
reported with rituximab, which effectively depletes B
lymphocytes. Splenectomy is not useful in cold agglutinin
disease.
 Paroxysmal Cold Hemoglobinuria

 Paroxysmal cold hemoglobinuria is mediated by the

Donath-Landsteiner (D-L) hemolysin, which is an IgG
cold-reactive autoantibody with anti-P specificity.
 In vitro, the D-L antibody binds to RBCs in the cold, and
the RBCs are lysed by complement as the temperature is
increased to 37°C.
 Paroxysmal Cold Hemoglobinuria

 A similar sequence is thought to occur in vivo as RBCs

move from the cooler extremities to warmer parts of the
circulation.
 Most reported cases are self-limited; many patients
experience only one paroxysm of hemolysis.
 Paroxysmal Cold Hemoglobinuria

 Congenital or acquired syphilis was once the most common

underlying cause of paroxysmal cold hemoglobinuria, but
currently, most cases are associated with nonspecific viral
infections.
 Treatment includes transfusion for severe anemia and
avoidance of cold ambient temperatures.
 References

 Nelson Textbook of Pediatrics 21st edition