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A brief Journey with AIHA

Dr. Maruf Rumi

phase-B resident

Dept. of Haematology

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Case scenario

Problem based discussion

Brief topic presentation

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Mr. Ujjal Das, 25 years old male, is a diagnosed case of coomb’s negative AIHA since January 2020 on the basis of initial-

Clinical presentation &
Lab parameters

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18/01/20 H/O 6 unit blood transfusion Wt 36 kg Spleen 12.5 cm		Tab.Prednisolone30mg×21days
08/02/20	Hb 8.2 g/dl RBC 3.1 mili/dl reticulcyte 5.09%	Tab.Prednisolpne40mg×21days Tab. Azathioprine 50 mg cont
10/03/20 Anaemia +	Hb 5.5 g/dl	2 unit RCC Tab.Dexa40mg×4d (1) Tab. Azathioprine 50 mg cont
23/03/20	Hb 9.4 g/dl RBC 3.53 mili/dl reticulcyte 3.88% LDH 230 Ferritin 4.58 Urine R/E- Normal	Tab. Dexameth40mg × 4d (2) Ferric carboxymaltose

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08/04/20	Hb 9.5 g/dl RBC 3.38 mili/dl	Tab. Dexameth 40 mg × 4d (3)
04/05/20	Hb 10.6 g/dl RBC 3.65 LDH 270 U/L Ferritin 53.91 ng/ml	Tab. Dexameth 40 mg × 4d (4)
31/05/20 Anaemia +	Hb 10.0 g/dl RBC 3.56 mili/dl ESR 15	Tab. Dexameth 40 mg × 4d (5)
21/06/20 Weakness Acne Anamia -	Hb 9.4 g/dl RBC 3.65 RBS 5.14 mmol/L	Tab. Dexameth 40 mg × 4d (6)

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14/07/20 Weakness ↓ appetite Anaemia	Hb 8.8 g/dl RBC 3.8 mili/dl Ret 4.01 % LDH 212 U/L	Tab. MMF 500mg BD ?Splenectony
15/08/20 Anaemia +	Hb 7.62 g/dl RBC 3.3 mili/dl Ret 4.01%	Tab. MMF 500mg BD Cap. Danazol 200mg daily Tab. Methylpred 16mg alt day
16/09/20 Anaemia +	Hb 9.1 g/dl RBC 4.26 mili/dl Ret 4.01% SGPT 264 U/L	Stop Danazol Tab. Methylpred 8mg alt day Tab. MMF 500mg BD
20/10/20	Hb 7.72 g/dl RBC 3.58 reticulcyte 6.55% LDH 178 SGPT 33 U/L Creatinine 0.72 mg/dl	Tab. Methylpred 8mg×21 day Tab. MMF 500mg BD

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21/11/20	Hb 8.1 g/dl RBC 3.72 Ret 6.00% RBS 4.68 mmol/L	Tab. Methylpred 12daily×21d Tab. MMF 500mg BD ??Rituximab
13/12/21 Weakness, headache Dysuria, yellow colouration Anaemia	Hb 7.42 g/dl RBC 3.5 mili/dl Ret 6.01% HbsAg - Urine R/E-Normal	Tab. Prednisiolone 40mg daily Rituximab 100mg weekly (1)
26/12/20 Anaemia +	Hb 8.1 g/dl RBC 4.04 mili/dl	Tab.Prednisiolone20mg alt day Rituximab 100mg weekly (2)
03/01/21 Fever, ↓ appetite Abd pain Anaemia +	Hb 7.22 g/dl RBC 3.56 reticulcyte 5.78% SGPT 41 U/L Urine R/E- Normal	Blood transfusion Tab. Prednisiolone 20mg alt day Rituximab 100mg weekly (3)

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10/01/21	Hb 8.7 g/dl RBC 3.8 Ret 2.64%	Tab. Prednisiolone 20mg alt day Rituximab 100mg weekly (4)
25/01/21	Hb 9.9 g/dl RBC 4.39 mili/dl Ret 4.00%	Tab. Prednisiolone 20mg×14d Rituximab 100mg weekly (5)
25/02/21 Anaemia +	Hb 7.02 g/dl RBC 4.8	Tab. Prednisiolone 20mg daily Cap. Danazol 200mg daily *Tab.Dexa 40mg×4d
08/04/21 Relapse	Hb 7.02 g/dl RBC 3.47 Ret 4.81% SGPT 437 U/L	Tab.Dexamethasone 16mg×14d Tab.Cyclophos50mgdaily 2nd opinion ?Plasma pharesis ?Plasma exchange
10/04/21 Anaemia + Wt 38 kg	Hb 9.1 g/dl	Blood transfusion Tab.Cyclophos50mgdaily Plasma exchange

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17/04/21	Hb 5.8 g/dl RBC 2.84 mili/L Bilirubin 1.5 mg/dl SGPT 24 U/L Creatinine 0.9 mg/dl Urien R/E- Normal	Blood transfusion Methyl prednisolone Cyclophosphamide oral
15/05/21	Hb 9.01 g/dl RBC 4.8	Cyclophosphamide
02/06/21	Hb 11.6 gm/dl RBC 4.0 mili/dl	Cyclophosphamide
12/06/21		+ Prednisolone 10mg
17/08/21	Hb 7.9 g/dl RBC 3.1 Ret 5.0% ALT, Creatinine- N	Dexamethsone 4mg daily×14d Cyclosporine 100mg BD
20/09/21 Refractory	Hb 7.82 gm/dl RBC 2.95 Creatinine 0.9mg/d Urine R/E- Normal	Cyclosporine

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Searching for history- 2 years back

Initial presentation- Fever, weakness, palpitation, G. bodyache
Icteric, Spleen 12.5 cm
3 unit BT
2.5 month Interval- another 3 unit BT
Further evaluation→ AIHA

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Now-

Unresponsive to treatment
Family history- NAD
No H/O blood loss
Total 11 unit blood transfusion
No significant drug history
Generalized dry, itchy, hyperpigmented skin with occasional eruptive lesion-

duration- since childhooh
spontaneous and persistant, resolve occasionally
no specific aggrevating or relieving factor

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short structured (?constiutional) with normal developmental milestone

mildly anaemia
mildly icteric
wt 36 kg
all vitals are normal
systemic examinations- NAD

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Splenectomy??

Re-evaluation?
skin changes?
structural presentation?

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Autoimmune hemolytic anemias (AIHAs) are rare, heterogeneous disorders characterized by the destruction of red blood cells through warm or cold antibodies.

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Ab may be-

autoAb produced by the pt directed against own red cell
alloAb-

produced by the pt directed against foreign red cell, eg. BT, drug
from outside directed against pt red cell, eg HDN

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Classification-

Autoimmune-

Warm Ab-

Primary- Idiopathci
2ndary- Autoimmune, LPD, Infection (EBV), Ovarian cyst, carcinoma, Drugs

Cold Ab-

CHAD
CAS- Infection (Mycoplasma), LPD

Donath Landsteiner Ab-

PCH- post viral, syphilis

Alloimmune-

Red cell Ag
Drug dependent

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Warm-acting Ab:

70%

All age group
female

37° C
Polyclonal
IgG
Panreacting
Rh (antie, anti-d, anti-c)

DAT positive

Subtype- Mixed, warm & cold Ab type

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Presentation-

Insidious onset- pallor, jaundice
acute- rapidly developing anaemia, HF in older
Life threatening anemia
extravascular haemolysis

Moderate increase unconjugated bilirubin
excess urinary urobilinogen

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Intravascular haemolysis-

dark urine
haemoglobinuria
haemosiderinuria

Marked icterus

liver disease
biliary tract obst (stone, sludge)

mild splenomegaly; marked splenomegaly (LPD)
marked reticulocytosis
polychromasis, spherocyte, nRBC
increased LDH

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Cold type-

15%

elderly

chronic course

predominantly IgM, bind 4°C, monoclonal/ polyclonal

against I (i) Ag
acrocynosis extremities, cold weather
anemia/ mild icterus
Lab- High MCV
agglutination
DAT +ve for C3d

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PCH-

occurs in children- viral infection
acute, intravascular haemolysis-

pale, dark urine, abdominal pain, collapse
self limiting, brisk haemolysis rare

against p Ag, polyclonal IgG
biphasic- reacts below 20°C, activates at 37°C

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Common Laboratory Features-

CBC with PBF, bilirubin
LDH, particularly isoenzyme 1
haptoglobin
urine hemoglobin or hemosiderin.

Universal signs of hemolysis-

decreased serum hemoglobin and hematocrit
increased serum LDH and unconjugated bilirubin
polychromasia and reticulocytosis.

Intravascular hemolysis-

increased free hemoglobinemia,
increased hemoglobinuria, hemosiderinuria, methemalbuminemia
decreased serum haptoglobin.

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False positive DAT	False negative DAT
< o.o1% healthy 0.03-8% Iatrogenic- IVIg, ATG, Daratumumab	IgM, IgA low Ab coating <100-300/cell low sensitivity improper sampling

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Management-

Warm type-

1. supportive-

Blood transfusion-

if clinical situation demands
Hb continues to fall
heart failure

(least incompetible blood, transfuse slowly, blood lacking Ag to which autoAb reacts)

IVIg
Folic acid

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2. First line treatment-

Prednisolone
Steroid + Rituximab

3. 2nd line treatment-

Splenectomy
Rituximab

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3rd line treatment-

Immunosuppressive drugs- azathioprine, danazol, cyclophosphamide, ciclosporin, MMF

steroid refractory pt
relapse following steroid
non responsive after splenectomy

(response usullay takes 4-6 weeks)

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