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OSCE PEDIATRICS
HEMATOLOGY SPOTS PART 1
www.dnbpediatrics.com
Anatomy of PS
www.dnbpediatrics.com
Red Cells
• Circular
• Mean cell diameter of 8
um(7.2-7.9)
• Central pallor does not
exceed more than one
half the diameter of the
cell.
• Ideal part of PS– Red cells
are just beginning to
touch and overlap.
www.dnbpediatrics.com
Platelets
• Granular basophilic forms
with a mean diameter of
1-2 um.
• Platelet adequacy:
- 8-15 platelets
(individually or in small
clumps) per 100x oil
immersion field or
- 1 platelet for every 10-30
RBCs.
www.dnbpediatrics.com
Neutrophils
• Round cells (10-14um)
• 2-5 lobes connected by a
thin thread of chromatin
• Chromatin stains purple
• Cytoplasm is pink with
purple granules
• Barr body
www.dnbpediatrics.com
Band or Stab forms
• Nucleus is U shaped
• Rudimentary lobes
connected by a thick
band rather than a
thread.
www.dnbpediatrics.com
Eosinophil
• Same size as
neutrophils
• 2 lobes
• Nucleus lightly stained
• Orange red granules
all over the cell.
www.dnbpediatrics.com
Basophil
• Slightly smaller than
neutrophils
• Has deeply basophilic
granules
www.dnbpediatrics.com
Monocyte
• Largest cells in
peripheral blood
• Nucleus– round,
kidney-shaped,oval or
lobulated and folded.
• Cytoplasm is light blue
or grey with fine
purple granules
www.dnbpediatrics.com
Lymphocyte
• Small-10 um in
diameter
• Large-20 um in
diameter
• Nucleus-large
rounded, densely
stained
• Cytoplasm-scanty,
pale to dark blue.
www.dnbpediatrics.com
N0RMAL SMEAR
www.dnbpediatrics.com
An 8 month old female child BONCM
brought with increasing pallor noticed
since the last 1 month.
• Diet h/o -- breast feeding with adequate
food
On examination,
• Wellgrown
• Pale and irritable
• L-1.5 cm,S-1.5 cm.
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Describe peripheral smear
• 2) Diagnosis on PS
• 3) Give 4 causes of hypochromic microcytic
• anemia
• 4) give 2 PS changes which are not present
that would point it to be a smear of thal trait.
www.dnbpediatrics.com
• 1) hypo,micro, aniso, poikilo, tear drop cell
• 2) hypo, micro anemia
• 3) iron def
• Thal
• Sideroblastic anemia
• Anemia of chronic disease
• HbH
• Atransferrinemia
• 4) basophilic stippling and target cells.
www.dnbpediatrics.com
After treatment
www.dnbpediatrics.com
• 1) Describe PS
• 2) Name 3 conditions in which dimorphic red
cell population is seen.
www.dnbpediatrics.com
• 1)Micro,hypo,macro, aniso,poikilo, tear drop
cells, polychromasia
• 2) iron def responding to iron therapy
• After the transfusion of normal blood to a
patient with a hypochromic anemia
• 3) Sideroblastic anemia
www.dnbpediatrics.com
• What would you do if the child with proved
iron def after receiving adequate iron therapy
comes back showing no response?
www.dnbpediatrics.com
• Suspect poor compliance
• Iron salt being used may be ineffective
• Increased blood losses
• GI causes
• Worm infestations
• H.Pylori
• Giardiasis
• Absorption defect
• Coeliac disease
• IBD
• Autoimmune gastritis
www.dnbpediatrics.com
 A 9 month male child has
• fever since 15 days on and off
• Pallor – 15 days
• No other significant history
 On examination,
• Liver--2 cm
• Spleen – 2.5cm
• Rest of the examination -- Normal
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Describe the specific PS change which
points it to being a homozygous Thal smear.
• 2) Name 4 conditions with increased Hb F.
• 3) Give the genotype of 4 transfusion
independent thal intermedia conditions.
www.dnbpediatrics.com
• 1) Nucleated red cells.
• 2) increased HbF
• HPFH
• δβ thalassemia
• Congenital red cell aplasia
• Congenital aplastic anemia(Blackfan-Diamond
and Fanconis anemia)
• JCML
• Some MDS
www.dnbpediatrics.com
• Slight increase in erythropoeitic stress
• (hemolysis, bleeding, recovery from acute BM
failure, pregnancy).
• 3) Genotype
• Some β+/β+ thal homozygotes
• Interaction of β0/ β0, β0/ β+ or β+/β+ with α
thal.
• Interaction of β0/ β or β+/β with triple α
www.dnbpediatrics.com
• HbH disease
• α 0 / Hb Constant Spring thal
• Β0/δβ or Β+/δβ thal compound heterozygotes
• δβ/ δβ thal
• Some cases of HbE/β thal and Hb Lepore/ β
thal
• Rare cases of heterozygotes for β thal
invol.exon 3 (dominant β thal)
www.dnbpediatrics.com
A 10 yr old male child BONCM
- Fever-low grade since 1 month
- Easy fatiguability since 15-20 days
-Tingling numbness in lower limbs since
10 days
On examination-
- Pallor ++
- Haemic murmur
- Other systems--normal
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Describe PS
• 2) Diagnosis on PS
• Which other PS changes should have been
present to support your diagnosis.
• 3) Name at least 2 other conditions with
neutrophilic hypersegmentation
www.dnbpediatrics.com
• 1) macro,aniso,poikilo,hypersegmented
neutrophils
• 2)megaloblastic anaemia
• Oval macrocytes,Baso stippling, HJ bodies,cabt
rings
• 3) hypersegmented neutrophils--- Uraemia
• Iron def
• Cytotoxic Rx esp. methotrexate
• Hydroxycarbamide Rx
www.dnbpediatrics.com
• 3) Define neutrophilic hypersegmentation
• 4) Give 6 other differentials of macrocytosis
www.dnbpediatrics.com
• 3) presence of 1 or more 6 lobed neutrophils or of 5 or
more neutrophils with 5 or more well separated lobes
among 100 segmented neutrophils.
• 4) macrocytic anemia--- megaloblastic anemia
• Aplastic anemia
• Myelodysplastic syn.
• Hydroxycarbamide Rx
• Chronic liver disease
• CDA type III
• Benign familial macrocytosis
• Hypothyroidism
• Increased erythropoeisis.
www.dnbpediatrics.com
• 2 weeks later,the child is clinically responding
but the neutrophilic hypersegmentation is still
persisting
• Would you worry and change your line of Mx
www.dnbpediatrics.com
2
1
5
4
3
www.dnbpediatrics.com
• Name the circled cells and name the
conditions in which they are seen
www.dnbpediatrics.com
• 1) Pencil cells--- Iron def
• 2) stomatocytes ---- hereditary stomatocytosis
• Southeast Asian ovalocytosis
• Liver disease
• Alcoholism
• Myelodysplastic syndromes
• Artifact
www.dnbpediatrics.com
• 3) Tear drop cell- Iron def anemia
• Congenital hemolytic anemias
• Microangiopathic hemolytic anemia
• Oxidant damage
• 4)Leptocyte---- iron def anemia
• Thal
• 5) Howell jolly body--- pernicious anemia
• After splenectomy,splenic atrophy
• Dyserythropoeitic anemia
• Severe iron def
www.dnbpediatrics.com
 A 6 yr old male child presents with fever of 2 days
duration with acute abdominal pain since 1 day.
He has never been symptomatic in the past.
 On examination,
• Pallor ++
• Icterus ++
• L3cm,S6cm
• Other systems—normal.
www.dnbpediatrics.com
CBC
- Hb—9.8gm% -WBC—10,500/cumm
- Hct—29.4% -P-55,L-45
- RBC—4 106 -Platelet—3.5 105
- MCV—85 fl
- MCH---27 pg -Retic--- 5.6%
- MCHC—34 %
- RDW– 14.6%
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) clinical diagnosis
• 2) Name 4 conditions with spherocytosis
• 3) Is Osmotic fragility test specific for
hereditary spherocytosis.
www.dnbpediatrics.com
• 1) Spherocytosis--- HS
• ABO hemolytic disease
• Autoimmune hemolytic
anemia
• Cl. Welchi sepsis
• 2) NO
www.dnbpediatrics.com
• 3) what is the mode of inheritance of HS
• 4) Name 2 specific test to diagnose Hereditary
spherocytosis.
• 5) Give 5 causes of false positive DAT test
www.dnbpediatrics.com
• 3) AD
• 4) Cryohemolysis test
• Memb. Protein analysis by Sodium dodecyl
sulfate polyacrylamide gel electrophoresis
• 5) alloantibody as in hemolytic disease of
newborn or after an incompatible Tx
• Drugs--- Quinidine,penicillin,cephalosporin
• Sepsis
• After ATG or ALG administration
www.dnbpediatrics.com
• Gp O platelets with high titre antiAor B to gp A
or B recipient.
• IvIg may contain ABO or antiD antibodies.
• As a result of antiphospholipid antibodies in
APLA syndrome and SLE.
• Sickle cell disease because of IgG coated red
cells.
www.dnbpediatrics.com
www.dnbpediatrics.com
• Sickling test on this patient is negative, explain
• Which test next will you perform
• Newborn screening ---- is it performed
routinely and how?
• If detected as sickle cell disease what steps
will you take next?
www.dnbpediatrics.com
• False negative
• Low Hb
• Outdated reagents
• Infants younger than 6 months
• Post Tx in which HbS level is < 20%.
• False positive---
• Severe leucocytosis
• Hyperproteinaemias
• Unstable Hb esp. after splenectomy
www.dnbpediatrics.com
• Newborn screening routinely performed in US and UK
• Dried blood spot samples--- High Performance Liquid
Chromatography or IsoElectricFocussing
• Umbilical cord blood samples---- Hb electrophoresis
using cellulose acetate or citrate agar or HPLC or IEF.
• Parents CBC and Hb electrophoresis
• Penicillin prophylaxis
• Repeat babys Hb electrophoresis at 6 months of age.
www.dnbpediatrics.com
• A 2.6 yr old asymptomatic child went for
cough/cold. CBC showed microcytosis,put on
hematinic.
• On follow up, inspite of being treated
adequately as a case of iron def anemia
microcytosis persisted.
• Referred to the hematologist.
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Name the cell
• 2) Why do they occur
• 3) 5 conditions in which target cells are seen
www.dnbpediatrics.com
• 1) Target cell
• 2)Disproportionately large surface compared to
volume
• 3) Liver disease
• Hereditary hypobetalipoproteinemia
• Iron def
• Thal
• Hbpathies--- HB C/β 0 thal
• HbC disease
www.dnbpediatrics.com
• Sickle cell anemia
• Sickle cell/HbC disease
• Sickle cell/ β thal
• Hb E disease
• Post splenectomy
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Name the intracellular inclusion
• 2) Name the conditions in which it is seen.
www.dnbpediatrics.com
• 1)Cabot ring
• 2) lead poisoning
• Pernicious anemia
• Hemolytic anemias
www.dnbpediatrics.com
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1) Name the cell
• 2) how will you investigate this patient
www.dnbpediatrics.com
• 1) Basophilic stippling
• 2) Megaloblastic anemia
• lead poisoning
• Thalassemia
• Infections
• Liver disease
• Unstable hemoglbins
• Pyrimidine nucleotidase 5 def
www.dnbpediatrics.com
• A 2 yr old child has diarrhoea with oliguria
with severe dehydration.The resident starts
treatment and sends the CBC which shows
low Hb with normal indices and low platelets.
www.dnbpediatrics.com
www.dnbpediatrics.com
• 1)Name the cell
• 2) Name 4 conditions in which these cells are
seen
• 3) Difference between acanthocyte and
echinocyte
•
www.dnbpediatrics.com
• 1)Schistocytes and acanthocytes
• 2) In certain genetic disorders( thal, CDA,
hereditary pyropoikilocytosis)
• Megaloblastic or dyserythropoeitic disorders
• Microangiopathic hemolytic anemia/cardiac
hemolytic anemias
• Direct thermal injury
www.dnbpediatrics.com
www.dnbpediatrics.com
• 3) Acanthocyte--- small no. of spicules of
inconsistent length, thickness and shape,
irregularly disposed over the surface of the cell.
• Seen in abnormal phospholipid metabolism
• Inherited abnormalities of RBC memb protein as
in McLeod phenotype
• Postsplenectomy
• Hyposplenism
• Liver disease
www.dnbpediatrics.com
www.dnbpediatrics.com
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  • 1. OSCE PEDIATRICS HEMATOLOGY SPOTS PART 1 www.dnbpediatrics.com
  • 3. Red Cells • Circular • Mean cell diameter of 8 um(7.2-7.9) • Central pallor does not exceed more than one half the diameter of the cell. • Ideal part of PS– Red cells are just beginning to touch and overlap. www.dnbpediatrics.com
  • 4. Platelets • Granular basophilic forms with a mean diameter of 1-2 um. • Platelet adequacy: - 8-15 platelets (individually or in small clumps) per 100x oil immersion field or - 1 platelet for every 10-30 RBCs. www.dnbpediatrics.com
  • 5. Neutrophils • Round cells (10-14um) • 2-5 lobes connected by a thin thread of chromatin • Chromatin stains purple • Cytoplasm is pink with purple granules • Barr body www.dnbpediatrics.com
  • 6. Band or Stab forms • Nucleus is U shaped • Rudimentary lobes connected by a thick band rather than a thread. www.dnbpediatrics.com
  • 7. Eosinophil • Same size as neutrophils • 2 lobes • Nucleus lightly stained • Orange red granules all over the cell. www.dnbpediatrics.com
  • 8. Basophil • Slightly smaller than neutrophils • Has deeply basophilic granules www.dnbpediatrics.com
  • 9. Monocyte • Largest cells in peripheral blood • Nucleus– round, kidney-shaped,oval or lobulated and folded. • Cytoplasm is light blue or grey with fine purple granules www.dnbpediatrics.com
  • 10. Lymphocyte • Small-10 um in diameter • Large-20 um in diameter • Nucleus-large rounded, densely stained • Cytoplasm-scanty, pale to dark blue. www.dnbpediatrics.com
  • 12. An 8 month old female child BONCM brought with increasing pallor noticed since the last 1 month. • Diet h/o -- breast feeding with adequate food On examination, • Wellgrown • Pale and irritable • L-1.5 cm,S-1.5 cm. www.dnbpediatrics.com
  • 14. • 1) Describe peripheral smear • 2) Diagnosis on PS • 3) Give 4 causes of hypochromic microcytic • anemia • 4) give 2 PS changes which are not present that would point it to be a smear of thal trait. www.dnbpediatrics.com
  • 15. • 1) hypo,micro, aniso, poikilo, tear drop cell • 2) hypo, micro anemia • 3) iron def • Thal • Sideroblastic anemia • Anemia of chronic disease • HbH • Atransferrinemia • 4) basophilic stippling and target cells. www.dnbpediatrics.com
  • 17. • 1) Describe PS • 2) Name 3 conditions in which dimorphic red cell population is seen. www.dnbpediatrics.com
  • 18. • 1)Micro,hypo,macro, aniso,poikilo, tear drop cells, polychromasia • 2) iron def responding to iron therapy • After the transfusion of normal blood to a patient with a hypochromic anemia • 3) Sideroblastic anemia www.dnbpediatrics.com
  • 19. • What would you do if the child with proved iron def after receiving adequate iron therapy comes back showing no response? www.dnbpediatrics.com
  • 20. • Suspect poor compliance • Iron salt being used may be ineffective • Increased blood losses • GI causes • Worm infestations • H.Pylori • Giardiasis • Absorption defect • Coeliac disease • IBD • Autoimmune gastritis www.dnbpediatrics.com
  • 21.  A 9 month male child has • fever since 15 days on and off • Pallor – 15 days • No other significant history  On examination, • Liver--2 cm • Spleen – 2.5cm • Rest of the examination -- Normal www.dnbpediatrics.com
  • 23. • 1) Describe the specific PS change which points it to being a homozygous Thal smear. • 2) Name 4 conditions with increased Hb F. • 3) Give the genotype of 4 transfusion independent thal intermedia conditions. www.dnbpediatrics.com
  • 24. • 1) Nucleated red cells. • 2) increased HbF • HPFH • δβ thalassemia • Congenital red cell aplasia • Congenital aplastic anemia(Blackfan-Diamond and Fanconis anemia) • JCML • Some MDS www.dnbpediatrics.com
  • 25. • Slight increase in erythropoeitic stress • (hemolysis, bleeding, recovery from acute BM failure, pregnancy). • 3) Genotype • Some β+/β+ thal homozygotes • Interaction of β0/ β0, β0/ β+ or β+/β+ with α thal. • Interaction of β0/ β or β+/β with triple α www.dnbpediatrics.com
  • 26. • HbH disease • α 0 / Hb Constant Spring thal • Β0/δβ or Β+/δβ thal compound heterozygotes • δβ/ δβ thal • Some cases of HbE/β thal and Hb Lepore/ β thal • Rare cases of heterozygotes for β thal invol.exon 3 (dominant β thal) www.dnbpediatrics.com
  • 27. A 10 yr old male child BONCM - Fever-low grade since 1 month - Easy fatiguability since 15-20 days -Tingling numbness in lower limbs since 10 days On examination- - Pallor ++ - Haemic murmur - Other systems--normal www.dnbpediatrics.com
  • 29. • 1) Describe PS • 2) Diagnosis on PS • Which other PS changes should have been present to support your diagnosis. • 3) Name at least 2 other conditions with neutrophilic hypersegmentation www.dnbpediatrics.com
  • 30. • 1) macro,aniso,poikilo,hypersegmented neutrophils • 2)megaloblastic anaemia • Oval macrocytes,Baso stippling, HJ bodies,cabt rings • 3) hypersegmented neutrophils--- Uraemia • Iron def • Cytotoxic Rx esp. methotrexate • Hydroxycarbamide Rx www.dnbpediatrics.com
  • 31. • 3) Define neutrophilic hypersegmentation • 4) Give 6 other differentials of macrocytosis www.dnbpediatrics.com
  • 32. • 3) presence of 1 or more 6 lobed neutrophils or of 5 or more neutrophils with 5 or more well separated lobes among 100 segmented neutrophils. • 4) macrocytic anemia--- megaloblastic anemia • Aplastic anemia • Myelodysplastic syn. • Hydroxycarbamide Rx • Chronic liver disease • CDA type III • Benign familial macrocytosis • Hypothyroidism • Increased erythropoeisis. www.dnbpediatrics.com
  • 33. • 2 weeks later,the child is clinically responding but the neutrophilic hypersegmentation is still persisting • Would you worry and change your line of Mx www.dnbpediatrics.com
  • 35. • Name the circled cells and name the conditions in which they are seen www.dnbpediatrics.com
  • 36. • 1) Pencil cells--- Iron def • 2) stomatocytes ---- hereditary stomatocytosis • Southeast Asian ovalocytosis • Liver disease • Alcoholism • Myelodysplastic syndromes • Artifact www.dnbpediatrics.com
  • 37. • 3) Tear drop cell- Iron def anemia • Congenital hemolytic anemias • Microangiopathic hemolytic anemia • Oxidant damage • 4)Leptocyte---- iron def anemia • Thal • 5) Howell jolly body--- pernicious anemia • After splenectomy,splenic atrophy • Dyserythropoeitic anemia • Severe iron def www.dnbpediatrics.com
  • 38.  A 6 yr old male child presents with fever of 2 days duration with acute abdominal pain since 1 day. He has never been symptomatic in the past.  On examination, • Pallor ++ • Icterus ++ • L3cm,S6cm • Other systems—normal. www.dnbpediatrics.com
  • 39. CBC - Hb—9.8gm% -WBC—10,500/cumm - Hct—29.4% -P-55,L-45 - RBC—4 106 -Platelet—3.5 105 - MCV—85 fl - MCH---27 pg -Retic--- 5.6% - MCHC—34 % - RDW– 14.6% www.dnbpediatrics.com
  • 41. • 1) clinical diagnosis • 2) Name 4 conditions with spherocytosis • 3) Is Osmotic fragility test specific for hereditary spherocytosis. www.dnbpediatrics.com
  • 42. • 1) Spherocytosis--- HS • ABO hemolytic disease • Autoimmune hemolytic anemia • Cl. Welchi sepsis • 2) NO www.dnbpediatrics.com
  • 43. • 3) what is the mode of inheritance of HS • 4) Name 2 specific test to diagnose Hereditary spherocytosis. • 5) Give 5 causes of false positive DAT test www.dnbpediatrics.com
  • 44. • 3) AD • 4) Cryohemolysis test • Memb. Protein analysis by Sodium dodecyl sulfate polyacrylamide gel electrophoresis • 5) alloantibody as in hemolytic disease of newborn or after an incompatible Tx • Drugs--- Quinidine,penicillin,cephalosporin • Sepsis • After ATG or ALG administration www.dnbpediatrics.com
  • 45. • Gp O platelets with high titre antiAor B to gp A or B recipient. • IvIg may contain ABO or antiD antibodies. • As a result of antiphospholipid antibodies in APLA syndrome and SLE. • Sickle cell disease because of IgG coated red cells. www.dnbpediatrics.com
  • 47. • Sickling test on this patient is negative, explain • Which test next will you perform • Newborn screening ---- is it performed routinely and how? • If detected as sickle cell disease what steps will you take next? www.dnbpediatrics.com
  • 48. • False negative • Low Hb • Outdated reagents • Infants younger than 6 months • Post Tx in which HbS level is < 20%. • False positive--- • Severe leucocytosis • Hyperproteinaemias • Unstable Hb esp. after splenectomy www.dnbpediatrics.com
  • 49. • Newborn screening routinely performed in US and UK • Dried blood spot samples--- High Performance Liquid Chromatography or IsoElectricFocussing • Umbilical cord blood samples---- Hb electrophoresis using cellulose acetate or citrate agar or HPLC or IEF. • Parents CBC and Hb electrophoresis • Penicillin prophylaxis • Repeat babys Hb electrophoresis at 6 months of age. www.dnbpediatrics.com
  • 50. • A 2.6 yr old asymptomatic child went for cough/cold. CBC showed microcytosis,put on hematinic. • On follow up, inspite of being treated adequately as a case of iron def anemia microcytosis persisted. • Referred to the hematologist. www.dnbpediatrics.com
  • 52. • 1) Name the cell • 2) Why do they occur • 3) 5 conditions in which target cells are seen www.dnbpediatrics.com
  • 53. • 1) Target cell • 2)Disproportionately large surface compared to volume • 3) Liver disease • Hereditary hypobetalipoproteinemia • Iron def • Thal • Hbpathies--- HB C/β 0 thal • HbC disease www.dnbpediatrics.com
  • 54. • Sickle cell anemia • Sickle cell/HbC disease • Sickle cell/ β thal • Hb E disease • Post splenectomy www.dnbpediatrics.com
  • 56. • 1) Name the intracellular inclusion • 2) Name the conditions in which it is seen. www.dnbpediatrics.com
  • 57. • 1)Cabot ring • 2) lead poisoning • Pernicious anemia • Hemolytic anemias www.dnbpediatrics.com
  • 60. • 1) Name the cell • 2) how will you investigate this patient www.dnbpediatrics.com
  • 61. • 1) Basophilic stippling • 2) Megaloblastic anemia • lead poisoning • Thalassemia • Infections • Liver disease • Unstable hemoglbins • Pyrimidine nucleotidase 5 def www.dnbpediatrics.com
  • 62. • A 2 yr old child has diarrhoea with oliguria with severe dehydration.The resident starts treatment and sends the CBC which shows low Hb with normal indices and low platelets. www.dnbpediatrics.com
  • 64. • 1)Name the cell • 2) Name 4 conditions in which these cells are seen • 3) Difference between acanthocyte and echinocyte • www.dnbpediatrics.com
  • 65. • 1)Schistocytes and acanthocytes • 2) In certain genetic disorders( thal, CDA, hereditary pyropoikilocytosis) • Megaloblastic or dyserythropoeitic disorders • Microangiopathic hemolytic anemia/cardiac hemolytic anemias • Direct thermal injury www.dnbpediatrics.com
  • 67. • 3) Acanthocyte--- small no. of spicules of inconsistent length, thickness and shape, irregularly disposed over the surface of the cell. • Seen in abnormal phospholipid metabolism • Inherited abnormalities of RBC memb protein as in McLeod phenotype • Postsplenectomy • Hyposplenism • Liver disease www.dnbpediatrics.com