Autoimmune hemolytic anemia in children

1. AUTO IMMUNE HAEMOLYTIC A

2. CONTENT
Introduction
Epidemiology
Clinical Manifestation
 Symptoms
 Diagnosis
Immunological basis
Treatments

3. INTRODUCTION
 Autoimmune Hemolytic Anemia (AIHA) is characterized
by an abnormal production of antibodies that bind to
Antigens on the erythrocyte surface. These antibodies
then leads to the
destruction of RBC’s thus shortening their life span.
 If this destruction is at a high enough rate, & exceeds
the bone marrow’s capacity to regenerate RBC’s, the
patient develops anemia and the associated signs
and symptoms.
 AIHA can be primary, where no evidence for a
secondary causative disorder exits; or secondary
in which hemolytic anemia is directly attributable to
another systemic disease.

4. EPIDEMIOLOGY
AIHA is a fairly uncommon disorder, with
estimates of the incidence at 1-3 cases per
100,000 people per year.
Primarily found in adults (more severe)
Also in children with primary immunodeficiency
Major is idiopathic
Secondary – malignant lymphoproliferative
diseases, drugs, and viral infections

5. CLASSIFICATION OF AUTOIMMUNE HEMOLYTIC
ANEMIA
1. Warm Autoimmune Hemolytic Anemia
2. Cold Autoimmune Hemolytic Anemia
 Cold Agglutinin Syndrome
Paroxysmal Cold Hemoglobinuria
3. Mixed-type Autoimmune Hemolytic
Anemia
4. Drug-induced Immune Hemolytic Anemia

6. 1) WARM AUTOIMMUNE HEMOLYTIC ANEMIA
 In the warm antibody type, the autoantibodies attach to
and destroy red blood cells at temperatures equal to or in
excess of normal body temperature.
 It is the most common form of autoimmune hemolytic
anemia (AIHA); more common among women.
 Primarily due to extravascular hemolysis
 Usually associated with the development of IgG (also IgA
& IgM)
 Ab’s bind to the surface of the RBC membrane
 Ab is activated at warm temperature of 37 degrees celcius
 Maybe either Primary or Secondary in etiology
 Primary - Idiopathic in nature
 Secondary – Due to an underlying disease (eg:
lymphoproliferative disorders, autoimmune disorders
etc.)

7. 2) COLD AUTOIMMUNE HEMOLYTIC
ANEMIA
 In the cold antibody type, the autoantibodies become
most active and attack red blood cells only at temperatures
well below normal body temperature.
 Caused by Cold agglutination syndome (CAS) or
Paroxysmal cold hemoglobinuria (PCH)
 Mainly affects middle-aged or elderly
 Occurs due to the development of of an IgM antibody
 Antibody is active at cold temperature (4 degrees
celcius) and not usually physiologically significant
 Either primary or secondary in etiology
 Primary - Idiopathic in nature
 Secondary – due to an underlying disease

8. MECHANISM OF DESTRUCTION 
 Intravascular hemolysis
 IgM antibodies activate the compliment system
resulting in cytolysis
 Extravascular hemolysis
 C3b & iC3b rather than the fc portion of IgM
are recognized
 Hemolysis occurs in the liver via kuppfer cells

9.  Cold agglutination syndrome
(CAS)
• Cold agglutinin disease (cold antibody disease) is
caused by autoantibodies that react at
temperatures <37° C.
• Causes includeInfections (especially mycoplasmal
pneumonias or
infectious mononucleosis)
• Lymphoproliferative disorders (antibodies are usually
directed against the I antigen)
• Idiopathic (usually associated with a clonal B-cell
population)
• Infections tend to cause acute disease, whereas
idiopathic disease
(the common form in older adults) tends to be chronic.
• The hemolysis occurs largely in the extravascular
mononuclear phagocyte system of the liver and

10.  Paroxysmal cold hemoglobinuria
(PCH)
• Paroxysmal cold hemoglobinuria is a rare type of cold
antibody hemolytic anemia. Destruction of red blood
cells results from exposure to cold. (28 – 31 degrees
celcius)
• Occurs more in children
• Antibody involved is IgG
• RBC’s may be destroyed even when cold exposure is
limited to a small area of the body, such as when the
person drinks cold water or washes hands in cold water.
• Intravenous hemolysis occurs (
• It occurs most often after a bacterial infection
(syphilis, mycoplasma pneumoniae) or a viral illness
(measles, mumps, influenza etc.). Can be caused due
to vaccines as well.

11. 3) MIXED-TYPE AUTOIMMUNE HEMOLYTIC
ANEMIA
• Features similar to both WAIHA & CAS
• Both IgG & C3d are detected
• IgG – warm antibody
• C3d – activated by IgM cold autoantibody
• Idiopathic
• Secondary (lymphoproliferative disorders, autoimmune
disorders)
4)DRUG INDUCED IMMUNE HEMOLYTIC
ANEMIA
• Antibodies directed against or one of its metabolites
• All may involve IgG & C3
• Mechanisms:
• Autoimmune type
• Drug adsorption type

12. IMMUNOLOGICAL
VIEW

13. Warm Autoimmune Hemolytic Anemia
• IgG binds to RBC surface antigens
• This drives monocytes & macrophages to
grab & pick off portions of RBC
membrane
• RBCs become spherocytes
• Destructed in spleen
EXTRAVASCULAR
HEMOLYSIS

14.  Cold Agglutination Disease
• In cold temperature, IgM binds to polysaccharide
region of glycoproteins on RBC surface
• This triggers complement system to lyse RBC
INRAVASCULAR HEMOLYSIS
• If complement system fails to form membrane attack
complex (when trigger is insufficient), complement
proteins deposit on RBC surface
• This opsonisation enhances RBC phagocytosis in
liver, spleen & lungs
EXTRAVASCULAR HEMOLYSIS

15. Paroxysmal Cold Hemoglobinuria
• During certain infections, microbes trigger
formation of Abs that react with the P antigen
of RBC surface
• After the infection, these polyclonal
anti-P autoantibody binds to P-Ag of
RBC in cold temperature
• When temperature increased, complement
system lyses these RBCs
INTRAVASCULAR HEMOLYSIS
• This leads to hemoglobinuria & anemia
whereas the anemia would either be mild or
severe

16. AIHA cannot be attributed to any single autoantibody.
To determine autoantibody/ies in a patient, direct Antiglobulin test (DAT) is
performed.
Classification of the Abs is based on their activity at different temperatures and
their etiology;
1) Warm Autoantibodies. - High activity at physiological temperature
(approximately 37 °C)
2) Cold Autoantibodies - Act best at temperatures of 0–4 °C
 Patients with cold-type AIHA, therefore, have higher disease activity when
body temperature falls into a hypothermic state.
Antibody becomes active when it reaches the limbs & opsonizes RBCs. When
these RBCs return to central regions, they are damaged by complement.
Patients may present with one or both types of Autoantibodies; if both are
present, it is called "mixed-type" AIHA.
ANTIBO
DY

17. CLINICSL FEATURES
The common symptoms are;
•Paleness of the skin
•Fatigue
•Fever
•Confusion
•Lightheadedness
•Dizziness
•Weakness or inability to do physical activity
Less common;
•Dark urine
•Yellowing of the skin and the whites of the eyes
(jaundice)
•Heart murmur
•Increased Heart rate
•Enlarged spleen

19. TESTS
• FBC (hemoglobin,
hematocrit)
• Absolute reticulocyte
count
• Coomb’s Test ( direct,
Indirect)
• Hemosiderin in the urine
• Protein electrophoresis

20. FULL BLOOD
COUNT
• Warm Antibody AIHA
Hematocrit level – less than
10%
Platelets are normal
• Cold AIHA
Exhibit mild to moderate anemia
Hematocrit level- low as 15-20%
• Drug induced AIHA
Similar to those warm antibody
AIHA

21. COOMB’S
TEST
Direct Coomb’s Test ( Direct Antiglobulin Test)
• This test is used to determine whether the RBC-binding
autoantibody (IgG) or compliment (C3) is bound to Ag
on RBC membranes.
• Coomb’s reagent is added to washed RBC’s from the
patient.
• If IgG or C3 is bound to RBC membranes, agglutination
occurs it is a positive result.

22. INDIRECT COOMBS TEST (INDIRECT
ANTIGLOBULIN TEST)
• The indirect antiglobulin (indirect Coomb’s) test is a
complementary test that consists of mixing the patient’s
plasma with normal RBCs to determine whether
autoantibodies are free in the plasma.
1. Normal RBCs are added to patient’s plasma
2. Then Coomb’s reagent is added
3. Agglutination occurs if autoantibodies are present in patient’s
plasma – positive test
• INDIRECT TEST is used to determine if there’s a
potential bad reaction to a blood transfusion
• DIRECT TEST is used to check for AUTOIMMUNE
HEMOLYTIC ANEMIA

23. TREATMEN
TS

24. TREATMENTS
• Corticosteroids & immunoglobulins are 2
common treatments.
• Initial medical treatment consists of prednisone
• Other options include rituximab, donazol,
cyclosphosphamide, azathioprine & ciclosporine.
• High dose immunoglobulin IV is possible; it
controls hemolysis, but the benefit is short lasting
(1-4 weeks); also expensive.
• If ineffective, splenectomy is considered.

25. FOR COLD
AGGLUTINATION
DISEASE
 REMOVAL OF UNDERLYING CAUSE IS IMPORTANT.
CAUSED
PATHOLOGY, TREAT IT].
 RITUXIMAB TREATMENT [MEDICATION FOR AUTOIM
DISEASES & TYPES OF CANCER].
 AVOIDING COLD WEATHER & COLD DRINKS IS IMPO
• FOR PAROXYMAL COLD HEMOGLOBINU
 TREAT THE INFECTIONS THAT LEAD TO
PAROXYSMAL COLD HEMOGLOBINURIA.
 I.E. IF CAUSED BY SYPHILIS, TREAT WITH NARROW
SPECTRUM PENICILLIN.

26. ROLE OF RITUXIMA