Extended clinical meeting on Auto immune hemolytic anemia

1. WELCOME TO extended
clinical meeting
Presenters:
DR. RENESHA ISLAM
YEAR-4 RESIDENT (PHASE-B)
PAEDIATRIC HAEMATOLOGY & ONCOLOGY DEPARTMENT

2. 2
PARTICULARS OF THE PATIENT
▸ Name: Alfi Bin Hadi
▸ Age: 10 years
▸ Sex: Male
▸ Address: Basabo
▸ DOA : 13/03/21
▸ DOE : 13/03/21
▸ Informant: Mother & Himself

3. 3
Presenting complaints
▸ Sudden onset of severe pallor for 10 days.
▸ Passage of dark colored urine for same
duration.
▸ Yellow discoloration of whole body for 8
days.

4. 4
History of present illness
According to the statement of the patient
himself and his mother, Alfi was
reasonably well 10 days back. Then he
developed severe pallor of sudden onset
and passage of dark colored urine for
same duration. He also developed yellow
discoloration of eyes which gradually
deepens and involved all over the skin
including palms and soles for 8 days.

5. CONTINUED..
5
 On query, Mother mentioned that Alfi had a
history of febrile episode and sore throat
about 11 days prior to this illness which
resolved spontaneously.
 He had no history of abdominal pain, back
pain, pruritus, skin rash, weight loss,
arthralgia, bleeding manifestation, no
history of taking any offending drugs, no
family history of gall stone or such type of
illness in his family.

6. CONT..
6
 For this reason, He got admitted in a private
hospital and treated with oral prednisolone
and 3 units of blood transfusion.
 But his condition did not improved. So, With
these above complaints, he was referred to
BSMMU for proper evaluation and further
management.

7. HISTORY OF PAST ILLNESS
7
• Alfi had a history of fever and sore throat
about 11 days prior to this illness.
• That time he only took oral antipyretics
and it resolved spontaneously.

8. BIRTH HISTORY
8
 Antenatal: Mother was on regular antenatal
check up. She had no H/O Fever, Rash, HTN,
DM, any features of Infections or taking any
offending drugs.
 Natal: Delivered at term by normal vaginal
delivery with birth weight 3250 gm.
 Postnatal : Uneventful. There was no H/O
neonatal jaundice.

9. 9
▸ Developmental History:
Age appropriate. He reads in class 4
with good academic performance.
▸ Immunization History:
Completely Immunized as per EPI
schedule.

10. 10
▸ Feeding History:
He is on family diet.
▸ Travel History:
Nothing significant.

11. FAMILY HISTORY
11
1st issue of his non consanguineous
parents. He had no family history of such
type of illness. His parents and only sib
are in good health.

12. SOCIO-ECONOMIC HISTORY
12
▸ He belongs to a upper middle class
family.
▸ Father is a businessman and average
monthly income is 60,000 taka. Mother is
a home maker.
▸ They live in brick build building, drink
purified water and use sanitary latrine.

13. TREATMENT HISTORY
13
▸ He was treated with oral prednisolone
2mg/kg/day for 7 days during his
admission period on that private
hospital along with 3 units of PRBC
transfusion.

14. GENERAL PHYSICAL EXAMINATION
14

15. GENERAL EXAMINATION
15
▸ Appearance : Ill looking
▸ Pallor: Severe
▸ Jaundice: Moderate
▸ Cyanosis
▸ Edema
▸ Dehydration
▸ Koilonychia Absent
▸ Clubbing
▸ Leukonychia

16. CONT….
16
▸ Lymph nodes: Not palpable.
▸ Bony tenderness : Absent.
▸ Skin survey : Normal.
▸ BCG mark : Present.
▸ Ex of eye, ear, nose & throat: Normal.
▸ Vital signs
▸ Pulse : 112 beat/min.
▸ BP : 100/60 mm Hg (Both
SBP& DBP lies between 50th and 90th centile)
▸ Respiratory Rate : 32 breaths/min.
▸ Temperature : 98.40F.

17. ANTRHOPOMETRY
17

18. Anthropometry
18
• Weight : 40kg (lies
between 75th -90th centile)
• Heigth : 138cm (lies
on 50th centile)
• BSA : 1.28 m2

19. SYSTEMIC EXAMINATION
19

20. HEMATOPOITIC SYSTEM
20
▸ Pallor: Severely pale.
▸ Jaundice: Moderately icteric.
▸ Bony tenderness: Absent.
▸ Lymph node examination: No
lymphadenopathy.
▸ Skin survey: Normal.
▸ Oral cavity: Healthy.

21. 21
▸ Liver: Not palpable.
▸ Spleen:
-6 cm from left costal margin along it’s
long axis
-Firm in consistency
-Splenic notch present.

22. CARDIOVASCULAR SYSTEM
22
▸ Inspection:
-No visible pulsation.
▸ Palpation:
-Position of trachea: Central
-Position of apex beat: 5th intercostal space
just medial to the mid clavicular line.
-Heart rate: 112 b/min
-Thrill : Absent
-P2 : Not palpable
-Left parasternal heave: Absent.

23. 23
CARDIOVASCULAR SYSTEM
▸ Auscultation:
-1st and 2nd heart sounds are audible in all
four areas.
-There is no murmur.

24. 24
RESPIRATORY SYSTEM
Inspection:
Respiratory Rate: 32 b/min
Shape of the chest: Normal
Chest Movement: Symmetrical.
Palpation:
Trachea: Centrally Placed
Chest Expansibility: Symmetrical
Vocal Fremitus: Normal.

25. 25
 Percussion:
○ Percussion Note: Resonant all
over the chest.
 Auscultation:
○ Breath Sound: Vesicular
○ No Added sound.
RESPIRATORY SYSTEM

26. Alimentary system examination
26
Mouth & oral cavity: Healthy.
Abdomen proper:
Inspection:
- Abdomen is distended.
- Umbilicus is centrally placed.
- No scar mark, visible pulsation or engorged
veins.
- Flanks are not full.

27. 27
Alimentary system examination
Palpation:
 Abdomen is non-tender, soft.
 Liver: Not palpable.
 Spleen :
-6cm from left costal margin along its
long axis
-Firm in consistency
-Splenic notch present.
 Fluid thrill: Absent.

28. 28
Alimentary system examination
▸ Percussion:
Percussion note tympanic.
No shifting dullness.
▸ Auscultation:
Bowel sound present.

29. GENITO-URINARY SYSTEM
29
▸ Kidneys: Not ballotable
▸ Urinary bladder : Not palpable
▸ Genitalia : Male type
▸ Hernial orifices: Intact.

30. 30
▸ Higher cerebral function: Intact.
▸ Examination of cranial nerves: Intact
▸ Motor function:
Bulk of muscle- normal
Tone – Normal
Power- Normal
Jerks- Normal
▸ Sensory: Intact
▸ Cerebellar function: Intact.
NERVOUS SYSTEM EXAMINATION

31. LOCOMOTOR SYSTEM EXAMINATION
31
▸ LOOK:
No joints are swollen, no periarticular wasting, No
scar mark present.
▸ FEEL:
Temperature- Normal
Tenderness: Absent
Fluctuation test- Not done
Patellar tap – Not done
▸ MOVE:
No restriction of movement.

32. SALIENT FEATURES
32
▸ Alfi, 10 years old boy, 1st issue of his non
consanguineous parents, immunized as per
EPI schedule, got admitted with the
complaints of sudden onset of severe pallor,
high colored urine for 10 days & jaundice for
8 days.
▸ He had a history of febrile episode and sore
throat about 11 days prior to this illness.

33. CONT…
 Alfi had no history of fever, abdominal
pain, back pain, pruritus, skin rash, no
family history of gallstones or taking any
offending drugs and none of his family
members suffer from this sort of illness.
33

34. 34
▸ On examination- Alfi was ill looking,
severely pale, moderately icteric, afebrile,
Anthropometrically well thrived, vitals were
within normal limit except tachycardia and
tachypnea present. Abdomen was
distended and splenomegaly present.

35. PROVISIONAL DIAGNOSIS
35

36. PROVISIONAL DIAGNOSIS
36
Hemolytic anemia
(most probably auto immune
hemolytic anemia)

37. DIFFERENTIAL DIAGNOSIS
37
▸ Paroxysmal nocturnal hemoglobinuria.
▸ Glucose 6 phosphate dehydrogenase
deficiency.

38. AUTO IMMUNE HEMOLYTIC ANEMIA
38
Points
in
Favor
Sudden onset of
severe pallor
Yellow discoloration
of whole body
High colored urine
Severe pallor
Moderately icteric
Splenomegaly

39. Paroxysmal nocturnal hemoglobinuria
39
Points
in
Favor
Sudden onset of pallor
Yellow discoloration of
whole body
High colored urine
Severe pallor
Moderately icteric
Splenomegaly
Points
Against
Urine
discoloration
not only in
early
morning or
night
No back pain
No abdominal
pain
No easy
bruising
No
hepatomegaly

40. G-6PD DEFICIENCY
40
Points
in
Favor
Male child
Sudden onset of
pallor
Yellow discoloration
of whole body
High colored urine
Severe pallor
Moderately icteric
Splenomegaly
Points
Against
No Family
History
No H/O
Neonatal
jaundice
No
hepatomegaly

41. investigations
41

42. INVESTIGATIONS DONE ON 06.03.21
42
▸ CBC: Hb- 4.5 gm/dl
Total count of WBC- 18,600/cmm
Platelet count- 2,70,000/cmm
▸ PBF: Features of hemolysis.
▸ Reticulocyte count: 4.7%
▸ Hb electrophoresis: Normal
▸ S. Bilirubin (Total): 5 mg/dl
▸ S. ALT: 125 U/L
▸ S. LDH: 525 U/L
▸ PT: 12 sec
▸ APTT: 36 sec

43. CONT….
43
▸ Coomb’s test: Direct- Positive
Indirect- Negative
▸ HBsAg: Negative
▸ Anti HCV: Negative
▸ IgG: 14.53 g/l (2.31-14.11 g/l)
▸ IgA: 0.95 g/l (.20-1.00 g/l)
▸ Anti-dsDNA: Negative
▸ ANA: Negative
▸ ICT Malaria: Negative
▸ Blood group: O (+ve)

44. INVESTIGATIONS DONE AFTER ADMISSION
44
▸ CBC: Hb- 5 gm/dl
TC of WBC- 17,170/cmm
DC of WBC- N: 70% L: 20% M:5% E: 3%
Platelet- 3,33,000/cmm
MCV- 102 fL
MCH- 38 pg
MCHC- 30 g/dl
▸ Reticulocyte count: 8 %

45. CONT….
45
▸ PBF-
-RBC: Anisocytosis, with many polychromatic
cells, spherocytes, schistocytes, nRBC, tear drop
cells.
-WBC: Increased, mature with above count and
distribution.
-Platelet: Normal.
▸ Coomb’s test- Direct positive.

46. CONT…
46
▸ S. bilirubin: Total- 5.5 mg/dl
Direct- 0.8 mg/dl
Indirect- 4.7 mg/dl
▸ SGPT: 50 U/l
▸ Prothombin time: Control-11.85sec
Patient- 12.15 sec
▸ APTT: Control- 32.85 sec
Patient- 30.15 sec
▸ INR: 1.08
▸ Random blood sugar: 6.2 mmol/l

47. “
Auto immune hemolytic
anemia
47
Final Diagnosis

48. TREATMENT
48
▸ Counseling
▸ Inj. Methyl prednisolone: 4 mg/kg/dose,
6hrly for 5days
▸ Tab. Prednisolone: 2mg/kg/day
▸ Tab. Folic acid.

49. FOLLOW UP ON 14/03/2021 d-02
49
Subjective Objective Assessment Plan
No new
complaints
Well alert
Afebrile
Moderately pale
Icteric
R/R- 22 b/min
Pulse - 88 b/min,
BP- 105/65 mmHg
Lungs- Clear
Heart- S1+S2+0
P/A/E- Soft, distended,
Non-tender
Spleen- 6 cm enlarged
Bowel & bladder habit-
Normal
Improving
CBC-
• Hb- 7.8 gm/dl
• TC of WBC-
12,200/cmm
• DC of WBC-
-N: 68%
-L: 25%
• Platelet-
2,29,000/cmm
Continue
same
treatment

50. Follow up on 18/03/2021 (d-06)
50
Subjective Objective Assesment Plan
No new
complaints
Well alert
Ill looking
Afebrile
Mildly pale
Anecteric
R/R- 16 b/min
H/R - 86 b/min,
BP- 100/70 mmHg
Lungs- Clear
Heart- S1+S2+0
P/A/E- Soft, distended,
Non-tender
Spleen- 2 cm enlarged
Bowel & bladder habit-
Normal
Improved
CBC-
• Hb- 11.9 gm/dl
• TC of WBC-
10,012 /cmm
• DC of WBC-
-N: 69%
-L: 25%
• Platelet-
2,19,000/cmm
Discharge
with advice

51. 51
4.5
5.5
6.2
6.8
6.5
5
7.8
9.2
10.3
11.9
12.5
13.5 13.7 13.5 13.7
0
2
4
6
8
10
12
14
16
Haemoglobin (gm/dl)
date
Oral
prednisolone
IV
methyl
pred
Oral
prednisolone
Stop
oral
pred

52. 52
4.7
8
4.2
2.86
2.4
1.77
1.07 1.05 1.02
0
1
2
3
4
5
6
7
8
9
Reticulocyte count %
date
Oral
prednisolone
Oral
prednisolone
IV
methyl
pred
Stop
oral
pred

53. Auto immune
hemolytic anemia
53

54. Causes of hemolytic anemia due to extra corpuscular
defect
54
Extra corpuscular
hemolytic anemia
Immune
Isoimmune Autoimmune
Idiopathic
(ex: warm antibody, cold
antibody)
Secondary
Nonimmune
Idiopathic Secondary

55. Auto immune hemolytic anemia
55
▸ Autoimmune hemolytic
anemia is a group of disorders
characterized by a malfunction
of the immune system that
produces autoantibodies, which
attack red blood cells as if they
were substances foreign to the
body.
▸ In AIHA shortened red cell
survival is caused by the action
of immunoglobulins, with or
without the participation of
complement on the red cell
membrane.

56. incidence
56
▸ Annual incidence: 1–3
cases/100,000.
▸ Approximately 0.2
cases/10,00,000 individuals
under 20 years of age.
▸ Not race or gender specific.
▸ Slightly more likely to
occur in females than
males.
WORLDWIDE PHO (BSMMU)
(2019-2021 till now)
2
admitted
3
admitted

57. Causes of auto immune hemolytic anemia
57
1. Idiopathic
Warm
antibody
Cold
antibody
Cold–warm
hemolysis
(Donath–Landsteiner
antibody)

58. 58
2) Secondary
○ Infection:
Viral- EBV, CMV, Herpes simplex, Measles, Varicella, HIV.
Bacterial- Streptococcal, E. coli, Mycoplasma.
○ Drugs and chemicals: Ceftriaxone, Penicillin, Quinine,
Quinidine, Tetracycline, Rifampin, Sulfonamides.
○ Hematologic disorders: Leukemias, Lymphomas,
Lymphoproliferative syndrome.
○ Immunopathic disorders: SLE, UC, Evans syndrome.
○ Tumors: Ovarian teratoma, Dermoids, lymphomas.
Causes of auto immune hemolytic anemia

59. 59
Mechanism of auto immune hemolytic anemia
COLD ANTIBODY
WARM ANTIBODY

60. 60
CLINICAL FEATURES
▸ Clinical presentation & course may
be either mild or more
complicated & severe.
▸ The symptoms may be of acute or
insidious onset.
▸ Most common: Sudden onset of
pallor, jaundice, dark urine,
splenomegaly, & hepatomegaly.
▸ Additional physical findings may be
present when the hemolytic
process is secondary to an
underlying disorder .

61. Laboratory investigation
1st level tests:
▸ Complete blood count:
Hemoglobin level: very low in fulminant
disease or normal in indolent disease.
Neutropenia and thrombocytopenia
(occasionally).
▸ Reticulocyte count: Reticulocytosis
common, although reticulocytopenia may
occur.
AIEOP guidelines for pediatric autoimmune hemolytic anemia

62. Peripheral blood film
Nucleated RBC
Spherocytes
Polychromatophilic
red cells
Agglutination

65. Laboratory findings
▸ S. Bilirubin level: Hyperbilirubinemia (Indirect)
▸ S. lactate dehydrogenase: Increased.
▸ Haptoglobin level: Markedly decreased.
▸ Urinary urobilinogen: Increased. Hemoglobinuria
especially at first presentation.
▸ Urinary hemosiderin.
▸ Osmotic fragility test: Increased and auto hemolysis
proportional to spherocytes.
▸ Blood Grouping and Rh typing.
▸ Liver and Renal function test.
AIEOP guidelines for pediatric autoimmune hemolytic anemia

66. ▸ Extensive RBC typing in anticipation of possible transfusion
▸ Immune-hematological investigations: C3, C4, CH50
▸ Auto-antibodies (ANA, anti DNA), anti-ph antibodies, RA test
- Thyroid function and anti-thyroid antibodies
- Lymphocyte sub populations (CD3, CD4, CD8, CD19, CD16)
- Double-ve T cells: CD3+, CD4-, CD8-
▸ HBV & HCV markers and HIV serology
▸ Coagulation screen blood test
▸ Serum total protein and protein electrophoresis
▸ Immunoglobulin class quantification
▸ C-reactive protein
▸ EBV, CMV, Parvovirus B19, HSV serology
▸ Other assessments for infectious diseases (clinically
appropriate)
Second level tests
AIEOP guidelines for pediatric autoimmune hemolytic anemia

67. Table : Characteristics of various forms of AIHA
Clinical
form
Frequency
%
DAT Ig class Thermal
Optimum
(°C)
Avidity
and ability
to fix
comple-
ment
Anti-
gen
Specifi-
city
Site of
heamolysis
Warm
antibody
60-70 IgG+ or
IgG/
C3d+
IgG 34-37 -/+ Anti-
Rh
Extra-
vascular
Cold
antibody
20-25 Neg or
C3d+
IgM 4-27 +++ Anti-I Extra-
vascular and
intra-
vascular
Cold
paroxysmal
hemoglobi-
nuria
6-12 Neg or
C3d+
IgG
Biphasic
Fixing 4-27
Lysis 34-37
+++ Anti-p Intra
vascular
Mixed
AEA
<5 IgG+ or
IgG/
C3d+ or
C3d-
IgG/ IgM IgG 34-37
IgM 4-27
++ Anti-
Rh
Anti-I
Extra-
vascular and
intra-
vascular
AIEOP guidelines for pediatric autoimmune hemolytic anemia

68. management
Blood Transfusion:
▸ Transfusion should be avoided.
▸ Nonetheless, using the “least income-
-patible” blood may be required in
properly selected situations in
order to avoid cardiopulmonary compromise. Conditions-
-Washed packed red cells should be used from donors
whose erythrocytes show the least agglutination in the
patient’s serum.
-Usually aliquots of 5 ml/kg are taken from a single unit
and transfused at a rate of 2 ml/kg/h.
-Concomitant use of high-dose corticosteroid therapy.

69. FIRST LINE THERAPY
Oral prednisolone
(1-2mg/kg/day for 3wks)
Continue for 1
week
Slow tapering
(6 month)
Prednisolone
dependence
Consider
different
diagnosis
2ND Line treatment
NR
Relapse
CR-PR
CR
NR
PR
>0.1-0.2mg/kg/day
Increase
prednisolone
back to
previous
dose
Relapse
<0.1-0.2mg/kg/day
Continue at
minimum effective
dose
Stop
therapy
CR
Continue at full
dose for 2 weeks
PR
AIEOP guidelines for pediatric autoimmune hemolytic anemia
Eventual additional
treatment in severe cases.
eg. Methyl pred, IVIG,
Plasma exchange

70. Second line THERAPY
AIEOP guidelines for pediatric autoimmune hemolytic anemia

71. MONITORING
This is potentially a life-threatening condition, So following must be
monitored carefully:
▸ Hemoglobin level (every 4 hours)
▸ Reticulocyte count (daily)
▸ Splenic size (daily)
▸ Hemoglobinuria (daily)
▸ Haptoglobin level (weekly)
▸ Direct antiglobulin test (DAT) (weekly)
Close attention should always be paid to supportive care issues
such as folic acid supplementation, hydration status, urine
output and cardiac status.

72. Clinical course
2 major groups of children with AIHA
▸ Acute course (50–70%)
▸ Chronic course (30–50%)
72

73. Prognosis
73
▸ Unpredictable.
▸ Response rate to glucocorticoids is 68.6% in acute
phase & even after relapse, 56.3% cases achieved
complete remission with glucocorticoids only.
This finding confirmed that steroid is the main
stay of treatment.
▸ Relapse usually occurs 0.5 to 36 months after
initial diagnosis with a median time of 4 months.

74. Mortality
▸ The adult mortality rate in one study was significantly
higher (28.7%) than the corresponding pediatric rate
(11%).
▸ When mortality occurs in children with AIHA it almost
always is seen in those with a chronic presentation.
▸ The cause of death is rarely from the anemia; more
commonly it is a complication of therapy or the
underlying medical condition.
74

75. SARS-COV-2 & AIHA
▸ Two previously healthy
children, each diagnosed with
an autoimmune cytopenia
associated temporarily with
SARS-CoV-2 viral infection,
one with acute ITP and one
with AIHA.
▸ Here, neither exhibited
symptoms of acute infection
with SARS-CoV-2 prior to or at
the time of presentation.
75
▸ They suggested that SARS
CoV-2 can trigger AIHA in
predisposed children.
▸ In the current epidemiologic
situation, upon the finding
of severe hemolytic anemia
without any apparent cause
in a previously healthy
child, SARS CoV-2 infection
should be ruled out.

76. THANK
YOU
ALL…..
76