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| Source: www.msdmanuals.com |
Definition
Autoimmune disease characterized through the existence of antibodies
again antigens at the surface of the RBCs, which lead to its agglutinating and hemolysis
in body temperatures
Etiology
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Viral infections (usually
in children)
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Autoimmune and connective
tissue diseases (particularly systemic lupus erythematosus, till 10% of patients).
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Immune deficiency diseases.
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Malignancies of the immune
system (eg, non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL) (till 11%
of patients), with a higher incidence in those treated with purine analogs
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Prior allogeneic blood
transfusion, hematopoietic cell transplantation, or solid organ transplantation.
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Drugs (penicillin,
methyldopa)
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Evans-Syndrom: the occurrence
of two or more hematologic immune cytopenia’s: most common: AIHA + Thrombocytopenia
Clinical manifestation
Signs and symptoms of anemia:
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exertional dyspnea, dyspnea
at rest
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varying degrees of fatigue
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signs and symptoms of the
hyperdynamic state, such as bounding pulses, palpitations, and "roaring in
the ears”.
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By severe anemia lethargy,
confusion and tachycardia
Clinical examination may reveal:
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Pallor
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Jaundice
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Moderate Splenomegaly
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Signs of cardiac
decompensation by severe anemia
Diagnosis
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HGB is reduced: usually
between 7 and 10 g/dl
MCHC is elevated due to the presence of
spherocytes
MCV is elevated due to reticulocytes
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Reticulocytes count is elevated
usually above 4-5%: may be absent (20-37%) by bone marrow suppression by viral
infections B19, medications and malignancies, or due to antibodies attacking
the RBCs normoblasts in bone marrow!
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LDH elevated
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Haptoglobin in reduced
(LDH elevation + Haptoglobin reduction is 90%
specific for AIHA, while normal LDH and Haptoglobin is 92% sensitive to ruling out
AIHA)
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peripheral blood smear
shows the presence of spherocytes, usually with an increased number of
polychromatophilic red cells (reticulocytes)
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Direct Coombs' test: it detects the antibodies attached to
the RBCs. Usually positive with anti-IgG, anti-C3, or both (positive in 99% in
patients with AIHA)
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Indirect Coombs' test: it detects the antibodies in the
plasma is generally of little value in this concern.
Differential Diagnosis
Hemolytic anemia of another causes:
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Drugs: drug history
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AIHA due to cold agglutinins:
relationship between anemia and exposure to cold, Direct coombs test usually positive
with anti-c3 and negative with anti-IgG, indirect coombs test reveals the presence
of IgM autoantibodies in Serum (cold agglutinins)
Therapy
Goal of the therapy is to control of the degree of anemia enough for
most activities without excessive compromise of immunologic responsiveness.
The therapy aims to either reducing
the amount of antibody being produced or reducing its efficiency in destruction
of the red cells:
Reducing
the amount of antibody:
1- Steroids:
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prednisolone 1 mg/kg
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remission accrues in 60-70%
of patients
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remission is to be seen
within 1-3 weeks
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signs of benefit are the
elevation of HGB.
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Tapering steroid should take
place once remission has been established (HGB> 10g/dl): Tapering-Schema:
Once HGB >10 g/dl
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Maintain Prednisolone 60 mg/day
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For one week
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If remission persistent
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Rapidly reduce the dose to 20 mg/day
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Over 2 weeks
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If remission persistent
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Maintain 20 mg/day
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For 4 weeks
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If remission persistent
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20 mg/day in alternation with 10 mg/day
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For 4 weeks
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If remission persistent
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20 mg/day every other day
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If remission persistent
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Reduce to 10 mg/day every other day
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Stop steroid when
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HGB, LDH, Haptoglobin, absolute reticulocytes within the
normal
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Control for recurrence for a number of months after stopping
steroids
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If at any step the remission cannot be maintained
other approaches should be considered:
2- Immunosuppressive
and cytotoxic agents:
Indications:
- lack of response to steroids
- Need of maintenance dose of steroids to
maintain remission higher than 15-20
mg/day
- inability to tolerate steroids
Azathioprine: 100-150 m/day, dose should
be adjusted to produce a fall in WBC to 3000/µl. Response begins after 1 month,
when 4 months without sufficient response then further therapy will be with no
effect. Relapse after dose reduction would be seen after 3-4 months
Cyclophosphamide: 100 mg/day p.o. or
500-700 mg/ 3-4 weeks i.v.
Common SE: hair loss, gonadal toxicity, bone
marrow suppression, bladder irritation with hematuria, and development of
myelodysplastic syndrome or leukemia
Cyclosporine: 5-10 mg/Kg/day divided
on 2 Doses/ mycophenolate mofetil: 500-1000 mg/day divided on 2
doses with increase to 1000-2000 mg: these agents can be used in resistant cases
of AIHA
3- Monoclonal
Antibodies:
Rituximab, Alemtuzumab:
experience is limited
Reducing the
Effectiviness of antibodies:
Splenectomy: remission in 60-70 %.
Intravenous gamma globulin: remission in only 40%, and after high
doses: 1000 mg/kg/ day i.v. for 5 days, to be used in very severe disease to establish
control
RBCs- transfusion: by severe anemia: full compatible
blood is difficult to find since the autoantibody will react with the antigen
on the surface of RBCs in almost all individuals.
“No patient with AIHA should die because of
difficulties in finding blood for transfusion”.
In general: consider steroids, then when no sufficient response
splenectomy, and at least when splenectomy unable, not helpful then consider immunosuppressive
agents
Complications
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development of a
lymphoproliferative disorder
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development of venous
thromboembolic disease
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