aiha for resident med
TRANSCRIPT
Autoimmune hemolytic anemiaKaipol Takpradit
Topic
PathophysiologyPresentationTreatment
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
IgG autoantibody
● Bind to RBC and cause hemophagocytosis in spleen
● Partial phagocytosis render RBC loss its membrane and produce microspherocyte
IgM autoantibody
● Fix complement on RBC cause intravascular hemolysis
● After fixation and lysis, C3b also cause destruction of RBC in liver (Kupffer cells)
Cause of secondary AIHA
● Drug: penicillin, fludarabine, methyldopa● Infection: mycoplasma● Tumor: lymphoma, ovarian dermal cyst,
renal CA● Other autoimmune disease: SLE
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
Agglutination in AIHA
IgM antibody can cause auto-agglutination due to its large size
While IgG need Coomb reagent to extend its size
Coomb test
● Coomb reagent is anti-human Fc portion of IgG immunoglobulin derived from rabbit
● Also called antiglobulin test
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
Coomb test
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
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
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
Guideline for Coomb positivity
Wintrobe's ed. 12th
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,
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
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
Treatment of warm/mixed type AIHAFirst 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
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
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
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
Other second line therapy
● Azathioprine● Cyclophosphamide● Cyclosporine● Mycophenolate mofetil● Danazol
All treatment may be combined with low dose steroid (Pred < 15 mg/day)
Treatment of cold type AIHA
● In most case associated with lymphoproliferative disease
● Less common ass. with autoimmune, infection, drugs (rarely)
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
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
FIN