Autoimmune hemolytic anemia (AIHA) can be primary or secondary. Primary AIHA has no obvious cause, while secondary is precipitated by conditions like drugs, infections, or tumors. AIHA is caused by autoantibodies binding to red blood cells (RBCs), which are then destroyed in the spleen or liver. Warm antibody AIHA is treated mainly with steroids, while cold antibody types are more resistant and associated with lymphoproliferative diseases. Treatment depends on the type and severity of AIHA.

1. Autoimmune hemolytic
anemia
Kaipol Takpradit

2. Topic
Pathophysiology
Presentation
Treatment

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

11. Coomb test

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

15. Guideline for Coomb positivity
Wintrobe's ed. 12th

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

27. FIN