3. AIHA pathophysiology
● Caused by autoantibody to self RBC
● Divided into
○ Primary AIHA: without obvious cause
○ Secondary AIHA: precipitated by some
condition
■ mainstay of treatment is removal of etiology
4. IgG autoantibody
● Bind to RBC and cause hemophagocytosis
in spleen
● Partial phagocytosis render RBC loss its
membrane and produce microspherocyte
5. IgM autoantibody
● Fix complement on RBC cause
intravascular hemolysis
● After fixation and lysis, C3b also cause
destruction of RBC in liver (Kupffer cells)
6. Cause of secondary AIHA
● Drug: penicillin, fludarabine, methyldopa
● Infection: mycoplasma
● Tumor: lymphoma, ovarian dermal cyst,
renal CA
● Other autoimmune disease: SLE
7. Antibody in AIHA
● Warm type
○ increase activity when near 37 c
○ usually IgG
● Cold type
○ increase activity when near 4c
○ usually IgM
○ cause auto-agglutination
○ fixed complement
● Mixed type
8. Agglutination in AIHA
IgM antibody can
cause auto-
agglutination due to
its large size
While IgG need
Coomb reagent to
extend its size
9. Coomb test
● Coomb reagent is anti-human Fc portion
of IgG immunoglobulin derived from
rabbit
● Also called antiglobulin test
10. Coomb test
● Most commercial Coomb reagent is
comprised of polyspecific antiglobulin
antibody
● Monospecific antibody for IgG, C3d, etc.
are available to identify type of AIHA
12. Coomb test
● Direct antiglobulin test (DAT)
○ detect IgG attached on patient's RBC
○ use in AIHA
● Indirect antiglobulin test (IAT)
○ detect IgG in patient's serum
○ the IgG must be lured to attach to control
RBC before perform DAT on the control RBC
○ use in cross-matching
13. Coomb test false positivity
● Poor technique (over centrifuged, dirty
test tube)
● Septicemia
● Drug induced non specific protein
adsorption (cephalosporin, clavulanic
acid)
● Wharton's jelly (non-specific adsorption)
● High paraproteinemia
● Alloantibody from transfused plasma
14. Coomb test false negativity
● Poor technique (incubation, cell washing,
centrifusion)
● IgA, IgM autoantibody
● Low-affinity antibody
● Too few antibody presence
● Prozone reaction from unlicensed product
(too many target antigen)
● Forget to apply antiglobulin reagent
16. Presentation of AIHA
● Acute anemia
● Increased reticulocyte count
● May have jaundice (indirect
hyperbilirubinemia; rarely > 5 mg/dL)
● Hepatosplenomegaly and
lymphadenopathy may present
● Other symptoms include edema, dark
urine, dizziness, confusion,
17. Other associated disease
Should aware of..
● Thrombocytopenia -> Evans syndrome
● Other autoimmune feature -> SLE
● Markedly large splenomegaly or
lymphadenopathy may indicate NHL
● Recently used drugs
● Patient may have increased risk of VTE
especially in association with lupus
anticoagulant or S/P splenectomy
18. Treatment of AIHA
● There is conflicting goal of treatment of
AIHA
● Generally accepted aim of treatment is Hb
10/dL
● Treatment goal must be weighted with
their side effect and cost
19. Treatment of warm/mixed type
AIHA
First line therapy is steroid
● Prednisolone 1 mkd (Pred)
● CR is achieved if Hb > 10 g/dL
● After CR reduce Pred by 50% (to 20-30
mg/day)
● Then reduce by 2.5-5 mg/day every
month
● Continue Pred 5 mg/day for 3-4 month
then stop if can remain in CR
20. Treatment of warm/mixed type
AIHA
Supportive treatment
● Folate supplement
● Antacid
● Calcium supplement
● Vitamin D supplement
● Bisphosphonate
● Monitor blood sugar (2-3 wk after Pred)
● Aware of VTE especially in association with
lupus anticoagulant or S/P splenectomy
21. Second line treatment
Indicate if
● Can not maintain acceptable Hb level
● Required Pred more than 15 mg/d
● Required Pred between 5-15 mg /d may
indicate second line treatment
22. Second line treatment
● Splenectomy
○ Response 38-82% (around 2/3)
○ Long term response vary around 50%
○ Pneumococcal vaccine is required 2 wk
before procedure and every 5 years
● Rituximab
○ Off label use
○ Dose 375 mg/m2 weekly x 4 doses
○ Response about 82%
○ But seem to relapse in 1 -3 years
23. Other second line therapy
● Azathioprine
● Cyclophosphamide
● Cyclosporine
● Mycophenolate mofetil
● Danazol
All treatment may be combined with low
dose steroid (Pred < 15 mg/day)
24. Treatment of cold type AIHA
● In most case associated with
lymphoproliferative disease
● Less common ass. with autoimmune,
infection, drugs (rarely)
25. Primary chronic cold agglutinin
disease (PAD)
● Have IgM monoclonal gammopathy or
lymphoma in marrow without overt
clinical sign
● Anemia is mild
● Treatment is usually not required
● Usually steroid and splenectomy resistant
● Most evidence of response are from
rituximab, though only in PR
26. Treatment of secondary AIHA
● SLE
○ Treatment is the same as primary AIHA
● CLL
○ Pred is the first-line (also in fludarabine asso.)
○ In active CLL case add chemo (chlorambucil,
R-CVP, etc.)
○ In refractory case rituximab and splenectomy
are indicated
● NHL
○ Treatment of NHL give a sustained response
