The patient has been admitted with fever for 2 months and pallorness for 2 months. Differential diagnoses include aplastic anemia, Fanconi anemia, and leukemia. Aplastic anemia is suggested by pancytopenia and bone marrow hypocellularity. It can be inherited or acquired from radiation, chemicals, drugs, or infections. Clinical features include bleeding, anemia symptoms, and risk of infection. Bone marrow biopsy will show a fatty, dilute specimen. Treatment options include growth factors, immunosuppression, stem cell transplant, or supportive care.

2. DR RAFIQUE ABBAS
FCPS POST GRADUATE TRAINEE
PAEDS MEDICINE
GMMMC AND HOSPITAL SUKKUR

3.  HISTORY
 EXAMINATION
 DIFFERENTIAL DIAGNOSIS
 DIAGNOSIS

4. History
• 10 yrs old Boy Adnan Ali S/O Imtiaz Ali having
weight 25 kg, resident of Saleh patt, admitted
through E.R in Paediatric ward with following
complaint:
Fever for 2 month
Pallorness for 2 month

5. HOPC
• According to statement of my patient’s mother
,he was in usual state of health 2 months back ,
then he develop fever which was low grade,
gradual in onset, continuous, short time being
relieved with anti pyretics medication, fever was
not associated with chills, rigors.
• Patient has also complaint of Pallorness, which
was progressive 1st appears at Palm and face than
gradually had been evident at all over the body
parts. It was not associated with bleeding, bone
pain or edema.

6. Cont.....
• During this period of 02 months they went to
nearby G.P couple of times ,where they were
treated with oral suspension and antipyretics,
proper investigations were not done.

7. SYSTEMIC INQUIRY
GENERAL: H/o weight loss, appetite and sleep
normal
GIT: no complain of Diarrhea , no h/o constipation
or blood in stool.
GENITOURINARY: No complain of Oligouria,
polyurea or haematuria.
CHEST: complain cough, but no history of
hemoptysis and shortness of breath.
CVS: no palpitation, chest pain or pedal edema .
LOCOMOTOR: No complain of pain, restricted
movements and tenderness of bone or joint.
CNS: No complain of fits, altered behavior,
headache, blackout, diplopia.

8. Insignificant

9.  Partially vaccinated
 (BCG Scar was absent)
FAMILY HISTORY:
 4 siblings, all healthy and alive
 Total 06 family members
 he is second product of consaguineous marriage, delivered via NVD
at home
 No history D.M, HTN, T.B,
 No h/o IV drug abuser in family
 No history of blood transfusion in family

10.  Child is school going
 Good performance in school
 Sleep, and bowel habits are normal
 Appetite is decreased

11.  lives in well ventilated house with 03 rooms and 1 washroom
 Father is labor by profession
 Use hand-pump water

12. NEUTRITIONAL HISTORY
• Required calories at this age are 1600kcal /day
but daily intake of my patient is 1300 kcal/day
There is no history of PICA.

13. Transfusion History
History of two times transfusion with whole
blood during this illness one 02 month back,
second 01 month back advised by GP, with no
any lab documention.

14.  Sick look male child,
conscious, alert,, child lying
on bed having cannula on left
hand with following vitals
 HR: 98 Beat/mint
 RR: 22 breath/mint
 Temp: 99 F
 Blood pressure: 110/70
 ( both sys & dia <90TH
centile)
SUBVITALS
A+, Cl-, J-, C- ,E-
Lymph nodes not palpable
BCG scar present
ANTHROPOMETRIC
MEASUREMENTS:
 weight= 25 kg (5th centile)
 Height=128 cm ( at 10th
Centile)

15. ABDOMEN:
INSPECTION:
distended, moving with respiration
Umbilicus centrally placed
No visible scar marks ,straie, veins or pulsations
Hernial orifices intact
PALPATION:
Soft, non-tender, no visceromegally
AUSCULTATION:
bowel sounds audible

16. SKIN EXAMINATION
• multiples rashes of purplish blue in color all
over body but more over the face and limbs of
different sizes ranges from 5mm to 1cm non
palpable non blanchable with regular margins
no oozing of blood.
• Having normal scalp hair and nails .

18.  ON INSPECTION:
Respiration abdomino-thoracic, chest moving equally with
respiration, no any scar mark, bulging or veins visible, r/r was
22/min…
 PALPATION AND PERCUSSION:
trachea centrally placed, further not significant.
 ON AUSCULTATION:
Normal vesicular breath, air entry equal on both sides….

19.  Chest normal shaped, no bulging scar mark
 No pulsations observed
 Apex beat at 4th inter costal space medial to midclavicular line
 No heave, thrill
 S1+ S2 audible
 No murmur
CNS EXAMINATION:
 INTACT

20. • 10 years old male child Adnan Ali S/O Imtiaz Ali, admitted in
paeds ward with c/o fever, fever not a/s with rigors and chills
for one month, Pallorness for one month. Having multiple rashes
of purplish blue in color all over body but more over the face and
limbs, ranges from 5mm to 1cm non palpable, non blanchable ,with
regular margins. Pt is partially vaccinated .On examination
patient is pale looking having weight 25 kg, height 110cm,BP
110/70,temp99 f .

22. BASED ON HISTORY AND EXAMINATON
THE DIFFERENTIALS ARE
• Aplastic anemia
• Fanconi anemia
• Leukemia

23. Investiga
tions

34. APLASTIC ANEMIA

35.  Aplastic anemia is pancytopenia with bone marrow
hypocellularity.
 Male and Female are affected with equal frequency.
 Age distribution is biphasic, with the major peak in the
teens and twenties and a second rise in older adults.
INTRODUCTION

36. CAUSES
INHERITED-
 Fanconi's anemia
 Dyskeratosis congenita
 Shwachman-Diamond syndrome
 Reticular dysgenesis
 Amegakaryocytic thrombocytopenia
 Familial aplastic anemias
 Preleukemia (monosomy 7)
 Nonhematologic syndrome (Down syndrome)

37. CAUSES
ACQUIRED-
Radiation
Drugs and chemicals
Viruses (non-A, non-B, non-C Hepatitis, EBV,
Parvovirus B19, HIV-1)
Immune diseases (Eosinophilic fasciitis, Thymoma,
Hyperimmunoglobulinemia, Graft-versus-host
disease)
Paroxysmal nocturnal hemoglobinuria.

38. RADIATION
 Marrow aplasia can be an acute sequale to
radiation.
 Nuclear accidents.
 MDS and leukemia, aplastic anemia, are late
effects of radiation.
CHEMICALS
 Benzene

39. DRUGS-
 Agents that regularly produce marrow depression as
major toxicity in commonly employed doses or normal
exposures: Cytotoxic drugs (alkylating agents,
antimetabolites, antimitotics), some antibiotics.
 Agents that frequently but not inevitably produce marrow
aplasia: Benzene
 Agents associated with aplastic anemia but with a
relatively low probability: Chloramphenicol,
Anticonvulsants.

40. INFECTIONS
-
 Hepatitis (non-A, non-B, non-C) is the most
common preceding infection.
 Infectious mononucleosis & parvo virus B19 in
some cases
 Rarely other bacterial & viral infections

41. FANCONI’s ANEMIA-
 Autosomal recessive disorder
 Chromosomes in Fanconi's anemia are peculiarly
susceptible to DNA cross-linking agent
 The most common, type A Fanconi's anemia, is
due to a mutation in FANCA.
 manifests as congenital developmental anomalies
(short stature, café au lait spots, and anomalies
involving the thumb, radius, and genitourinary
tract), progressive pancytopenia, and an increased
risk of malignancy

42. DYSKERATOSIS CONGENITA-
 X- linked, in some cases autosomal dominant
 mutations in genes of the telomere repair complex
 Characterized by Mucous membrane leukoplasia, dystrophic
nails, reticular hyperpigmentation, and the development of
aplastic anemia in childhood.
SHWACHMAN- DIAMOND SYNDRME-
 compound heterozygous mutations in SBDS
 Marrow failure + Pancreatic insufficiency and malabsorption.

43. PATHOPHYSIOLOGY
 Bone marrow failure results from severe damage to the
hematopoietic cell compartment.
 There is replacement of the bone marrow by fat.
 An intrinsic stem cell defect exists for the constitutional
aplastic anemias
 Extrinsic damage to the marrow follows massive physical
or chemical insults such as high doses of radiation and
toxic chemicals
 Immune mediators like Helper T cells, TNF, IFN-ϒ may be
involved in the pathogenesis.

44. CLINICAL PRESENTATION
 can appear seeming abruptly or have a more insidious
onset.
 Bleeding is the most common early symptom. Easy
bruising, oozing from the gums, epistaxis, heavy
menstrual flow, and sometimes petechie (massive
hemorrhage is unusual)
 Symptoms of anemia are also frequent, including
lassitude, weakness & shortness of breath.
 Infection (due to leukopenia) is an unusual first
symptom in aplastic anemia.

45. CLINICAL EXAMINATION
 Petechiae and ecchymoses
 Pallor
 Retinal hemorrhage
 Look for other features associated with inherited
causes
 Lymphadenopathy and splenomegaly are highly
atypical of aplastic anemia.

47. INVESTIGATIONS
BLOOD-
 Smear shows large erythrocytes and a paucity of
platelets and granulocytes.
 Reticulocytes are absent or few.
BONE MARROW-
 fatty biopsy specimen may be grossly pale
 Dilute smear
 “Dry tap" instead suggests fibrosis or myelophthisis

49. TREATMENT
 Hematopoietic growth factors
 Immunosuppression
 Stem cell transplantation
 Supplementation of blood products and supportive
care

50. Hematopoietic growth factors-
 Limited usefulness
Stem cell transplantation-
 This is the best therapy for the younger patient with a
fully histocompatible sibling donor.
 For allogeneic transplant from fully matched siblings,
long-term survival rates for children are approximately
90%.

51. Immunosuppression-
 As most of patients lack suitable donor, it is the
treatment of choice for them.
 ALG + Cyclosporine+ Corticostriods => induces
hematologic recovery in ≈ 65 % of cases.
 Relapse is frequent, usually after withdrawl of
cyclosporine.

52.  Methyl prednisolone alone is given in single dose of 5
mg/kg/day PO or I/V for 8 days followed by single
dose of 1 mg /kg/day for 6 days taper dose in next 6
days then discontinue, steroid response alone is 25 %.
 ALG is given as 40mg/kg/dose continuous I/V infusion
over 12 hours with methyl prednisolone 1mg/kg/day
I/V for 4 days .ALG alone gives about 50% response
rate.
 Cyclosporin is given orally in a dose of 8 mg/kg/day for
initial 14 days then 15mg/kg/day. Continue treatment
for minimum 3 months .

53. OTHER TREATMENT MODALITIES
 Intravenous immunoglobulins
 Anti thymocytic globulins
 Recombination human IL-3
 Gene therapy