Hematology lecture presentation of Pathology.ppt

Pediatric Hematology
Pediatric Hematology
Dr. Mohamed A. Obeid
Dr. Mohamed A. Obeidِ
ِ

Hemoglobin
Hemoglobin
640 million molecule of Hb / a RBC.
640 million molecule of Hb / a RBC.
Hb composed of 4 polypeptide chains.
Hb composed of 4 polypeptide chains.
Hb A has 2 alpha and 2 beta chains each
Hb A has 2 alpha and 2 beta chains each
with a haem group.
with a haem group.
Each Hb molecule combine 4 O
Each Hb molecule combine 4 O2
2 

oxyhemoglobin.
oxyhemoglobin.
Deoxyhemoglobin
Deoxyhemoglobin 
 2,3-DPG
2,3-DPG

Haem Synthesis
Haem Synthesis
Occurs in the mitochondria.
Occurs in the mitochondria.
Glycine + Succinyl Co-A
Glycine + Succinyl Co-A
 Protoporphyrin + Fe
Protoporphyrin + Fe

 haem.
haem.
Control of erythropoiesis:
Control of erythropoiesis:
1. hormones; erythropoietin, IL-3, stem cell
1. hormones; erythropoietin, IL-3, stem cell
factors, thyroxin and androgen.
factors, thyroxin and androgen.
2. metals; iron, mangenese and cobalt.
2. metals; iron, mangenese and cobalt.
3. Vit; B
3. Vit; B1
1,
, folate, C,E, B
folate, C,E, B6
6, thiamine.
, thiamine.
4. amino acids.
4. amino acids.

Haem Synthesis
Haem Synthesis
Fetus:
Fetus:
0-2 months yolksac
0-2 months yolksac
2-7 ,, liver, spleen
2-7 ,, liver, spleen
5-9 ,, bone marrow
5-9 ,, bone marrow
Infant: bone marrow
Infant: bone marrow
Adult : bone marrow(flat bone)
Adult : bone marrow(flat bone)
Extramedullary hemopoiesis:
Extramedullary hemopoiesis:
Hb made in liver& spleen outside fetal life.
Hb made in liver& spleen outside fetal life.

Hemoglobin Types
Hemoglobin Types
HbA; 2 Alpha- 2 Beta.
HbA; 2 Alpha- 2 Beta.
HbA
HbA2;
2; 2 Alpha- 2 Delta.
2 Alpha- 2 Delta.
HbF; 2 Alpha- 2 Gama.
HbF; 2 Alpha- 2 Gama.

Anemia
Anemia
Inadequate level of Hb.
Inadequate level of Hb.
Normal Hb range
Normal Hb range
Age
Age
Hb ( g/dl)
Hb ( g/dl)
Birth
Birth
15-23
15-23
2 weeks
2 weeks
13-19
13-19
2 months
2 months
9-13
9-13
6 months
6 months
11-14
11-14
1 year
1 year
11-14
11-14
2-6 years
2-6 years
11-13
11-13
6-18 years
6-18 years
11-16
11-16

Anemia
Anemia
Clinical manifestations
Clinical manifestations
Fatigue, headache, fainting.
Fatigue, headache, fainting.
Breathlessness, palpitations
Breathlessness, palpitations
General Signs; pallor, tachycardia, flow
General Signs; pallor, tachycardia, flow
murmur, cardiac failure, retinal hage
murmur, cardiac failure, retinal hage
( if severe)
( if severe)
Specific signs; Koilonychia (Fe def),
Specific signs; Koilonychia (Fe def),
Jaunice in hemolysis.
Jaunice in hemolysis.

Anemia
Anemia
Investigations:
Investigations:
Red cell indices;
Red cell indices;
size; MCV
size; MCV 
 normo, micro &
normo, micro &
macrocytic.
macrocytic.
Hb content ; MCH- MCHC
Hb content ; MCH- MCHC 
 normo
normo
and hypochromic.
and hypochromic.
Retics: normal = 1.5-2 %.
Retics: normal = 1.5-2 %.

Anemia
Anemia
Investigations:
Investigations:
Platelet &WBC: Low in pancytopenia.
Platelet &WBC: Low in pancytopenia.
Rise in Hage, hemoly infection.
Rise in Hage, hemoly infection.
Blood film
Blood film
 RBC morphology.
RBC morphology.
Bone marrow:
Bone marrow:
Aspiration
Aspiration
 smear of bone marrow to see
smear of bone marrow to see
developing cells.
developing cells.
Trephine
Trephine 
 core of marrow view architect,
core of marrow view architect,
cellularity & infilterates.
cellularity & infilterates.

Microcytic Hypochromic Anemia
Causes:
Causes:
1. Iron deficiency.
1. Iron deficiency.
2. Anemia of chronic illness.
2. Anemia of chronic illness.
3. Sideroblastic anemia ( congenital)
3. Sideroblastic anemia ( congenital)
4. Thalassemia.
4. Thalassemia.

Iron deficiency Anemia:
Iron deficiency Anemia:
The commonest anemia worldwide.
The commonest anemia worldwide.
Fe absorbed in duodenum & jejunum as
Fe absorbed in duodenum & jejunum as
Ferrous.
Ferrous.
Max Fe absorption 3-4 mg/day.
Max Fe absorption 3-4 mg/day.
Absrbed Fe transported in plasma as
Absrbed Fe transported in plasma as
transferrin ( B- globulin+ Fe)
transferrin ( B- globulin+ Fe)

Iron deficiency Anemia
Tow 3
Tow 3rd
rd
of Fe incorporated into Hb.
of Fe incorporated into Hb.
One 3
One 3rd
rd
in stores as ferritin ( tow 3
in stores as ferritin ( tow 3rd
rd
)
)
and hemosiderin ( one 3
and hemosiderin ( one 3rd
rd
).
).
Stores are in RE cells of liver, spleen &
Stores are in RE cells of liver, spleen &
bone marrow.
bone marrow.
A small fraction of ferritin circulates in
A small fraction of ferritin circulates in
serum.
serum.

Specific clinical features
Specific clinical features
Mouth:Painless glossitis, angular
Mouth:Painless glossitis, angular
stomatitis.
stomatitis.
Nails: Koilonychia, brittle and ridged.
Nails: Koilonychia, brittle and ridged.
GIT: Pharyngeal web ( Plummer- Vinson
GIT: Pharyngeal web ( Plummer- Vinson
syndrome), Pica, atrophic gastritis.
syndrome), Pica, atrophic gastritis.

Specific Investigations
Specific Investigations
a) Anemia
a) Anemia
1. RBC Indices & Film
1. RBC Indices & Film
Hypochromic, microcytic
Hypochromic, microcytic
Anisocytosis,
Anisocytosis,
Poikilocytosis.
Poikilocytosis.
Target and Pencil cells.
Target and Pencil cells.
Moderately raised Plts.
Moderately raised Plts.

2. serum Iron
2. serum Iron 
 decreased
decreased
3. TIBC
3. TIBC 
 Increased.
Increased.
4. serum ferritin
4. serum ferritin 
 decreased.
decreased.
5. free erythrocyte porphyrin
5. free erythrocyte porphyrin 
 increased.
increased.
6. Bone marrow:
6. Bone marrow:
no iron stores in macrophage
no iron stores in macrophage
no sidertic granules in erythroblasts.
no sidertic granules in erythroblasts.
small erythroblasts.
small erythroblasts.

b) Underlying causes
b) Underlying causes
Look for dietary deficiency.
Look for dietary deficiency.
Look for malabsorption.
Look for malabsorption.
Look for blood loss ( stool occult blood,
Look for blood loss ( stool occult blood,
hookworm ova, endoscopy, colonoscopy,
hookworm ova, endoscopy, colonoscopy,
Meckel’s scan hematuria)
Meckel’s scan hematuria)

Management
Management
Treat the cause.
Treat the cause.
Oral iron.
Oral iron.
Parenteral iron (rarely)
Parenteral iron (rarely)
 Anaphylaxis.
Anaphylaxis.
Blood transfusion
Blood transfusion 
 heart failure.
heart failure.

Sideroblastic Anemia
Sideroblastic Anemia
Anemia e’ hypochromic peripheral cell and
Anemia e’ hypochromic peripheral cell and
increased marrow iron & Ring Siderolasts.
increased marrow iron & Ring Siderolasts.
There is disordered hem synthesis.
There is disordered hem synthesis.
causes:
causes:
1. Inherited
1. Inherited
 X-linked.
X-linked.
2. Acquired
2. Acquired
 INH, alcohol, lead poisoning,
INH, alcohol, lead poisoning,
malabsorption, malignant disease of marrow.
malabsorption, malignant disease of marrow.
ttt: withdraw the cause
ttt: withdraw the cause
Pyridoxine, repeated Blood Transfusion.
Pyridoxine, repeated Blood Transfusion.

Macrocytic Anemia
Macrocytic Anemia
Tow types:
Tow types:
1) macrocytic;
1) macrocytic;
newborn
newborn
pregnancy
pregnancy
liver disease
liver disease
reticulocytosis
reticulocytosis
hypothyroidism
hypothyroidism

Macrocytic Anemia
Macrocytic Anemia
2) megaloblastic;
2) megaloblastic;
Vit B
Vit B12
12 deficiency
deficiency
Folate deficiency
Folate deficiency
DNA synthesis defect e.g. orotic aciduria
DNA synthesis defect e.g. orotic aciduria
In bone marrow Erythroblast e’ delayed nucleus
In bone marrow Erythroblast e’ delayed nucleus
maturation.
maturation.
Underlying cause; defective DNA synthesis.
Underlying cause; defective DNA synthesis.
WBC & Platelets may be deficient.
WBC & Platelets may be deficient.

Megaloblastic Anemia
Folate: In green vegetables, liver & kidney.
Folate: In green vegetables, liver & kidney.
Stores 3-4 month
Stores 3-4 month
Deficiency:
Deficiency:
- inadequate intake ( sp diet e.g. celiac)
- inadequate intake ( sp diet e.g. celiac)
- increased utilization
- increased utilization
 preterm, pregnancy,
preterm, pregnancy,
hemolysis,malignancy.
hemolysis,malignancy.
- increased loss in urine
- increased loss in urine
 acute liver dis
acute liver dis
- antifolate drugs
- antifolate drugs
 Phenytoin, methotrexate,
Phenytoin, methotrexate,
trimethprim.
trimethprim.

Vit B
Vit B12
12 :
:
In liver, fish & dairy products.
In liver, fish & dairy products.
Stores of 2-3 yrs.
Stores of 2-3 yrs.
Diet
Diet
 IF-B
IF-B12
12 
 terminal ileum
terminal ileum

absorbed
absorbed 
 plasma bound TC I & TC II
plasma bound TC I & TC II

Bone marrow.
Bone marrow.

Deficiency:
Deficiency:
a. low intake ( Vegans)
a. low intake ( Vegans)
b. impaired absorption
b. impaired absorption
- gastrectomy
- gastrectomy
- ileal resection
- ileal resection
- pernicios anemia
- pernicios anemia
c. abnormal metabolism
c. abnormal metabolism
- TC II def.
- TC II def.
- Nitrous oxide.
- Nitrous oxide.

Pernicious Anemia
Pernicious Anemia
IF deficiency
IF deficiency
a. congenital ( AR)
a. congenital ( AR)
b. association;
b. association;
blood gp A, Vitiligo, autoimmune thyroid,
blood gp A, Vitiligo, autoimmune thyroid,
Addison’s dis, atrophic gasteritis.
Addison’s dis, atrophic gasteritis.
Findings:
Findings:
Non- specific; Parietal cell Ab (90%).
Non- specific; Parietal cell Ab (90%).
Specific; IF Ab (50%).
Specific; IF Ab (50%).
NB. No Ab in congenital type.
NB. No Ab in congenital type.

Specific clinical features:
Specific clinical features:
- mouth; glossitis, angular stomatitis.
- mouth; glossitis, angular stomatitis.
- skin; jaundice,purpura, hyperpigmentatn.
- skin; jaundice,purpura, hyperpigmentatn.
- neuropathy
- neuropathy
 Vit B
Vit B12
12 def only.
def only.
- Subacute combined degeneratn of cord;
- Subacute combined degeneratn of cord;
progressive neuropathy of post & lateral
progressive neuropathy of post & lateral
columns( vibration & proprioceptn)
columns( vibration & proprioceptn)
Ataxia, hand & feet tingling
Ataxia, hand & feet tingling
Absent ankle jerks ( peripheral) increased knee jerks
Absent ankle jerks ( peripheral) increased knee jerks
( cord)
( cord)
Optic atrophy, retinal hage & dementia.
Optic atrophy, retinal hage & dementia.

Investigations;
Investigations;
- blood film
- blood film
 macrocytosis, low plt & wbc
macrocytosis, low plt & wbc
hypersegmented neutrphils (5 or> lobes)
hypersegmented neutrphils (5 or> lobes)
- bone marrow
- bone marrow
 megaloblastic changes.
megaloblastic changes.
- Schling test
- Schling test
 to diff vit B
to diff vit B12
12 low intake
low intake
from malabsorption & pernicious anemia.
from malabsorption & pernicious anemia.

Management;
Management;
B
B12
12 : im inj 6x 1000 Ug X3 wk then 3
: im inj 6x 1000 Ug X3 wk then 3
monthly injection
monthly injection
Folate : P.O. folic acid 1-5 mg.
Folate : P.O. folic acid 1-5 mg.

Hemolytic Anemia
Hemolytic Anemia
Increased RBC destruction.
Increased RBC destruction.
RBC lifespan is 120 days.
RBC lifespan is 120 days.
Causes:
Causes:
1. Hereditary:
1. Hereditary:
- membrane; Sphero & Elliptocyt
- membrane; Sphero & Elliptocyt
- metabolism; G6PD & PK def
- metabolism; G6PD & PK def
- Hb; HbS, Hbc, thalass.
- Hb; HbS, Hbc, thalass.

Hemolytic Anemia
Hemolytic Anemia
Causes cont;
Causes cont;
2. Acquired;
2. Acquired;
*immune;
*immune;
- autoimmune; (warm,cold Ab)
- autoimmune; (warm,cold Ab)
- alloimmune; BTreactns,HDN,transplat
- alloimmune; BTreactns,HDN,transplat
- drugs induced abs; e.g. quinine.
- drugs induced abs; e.g. quinine.
* RBC fragmentan syndromes
* RBC fragmentan syndromes
- prostheses e.g. cardiac valves.
- prostheses e.g. cardiac valves.
- microangiopathic; HUS,TTP,DIC.
- microangiopathic; HUS,TTP,DIC.
* systemic dis: e.g. liver, renal.
* systemic dis: e.g. liver, renal.
* infections; e.g. malaria.
* infections; e.g. malaria.

Hemolytic Anemia
Hemolytic Anemia
Clinical features:
Clinical features:
- pallor.
- pallor.
- jaundice
- jaundice
- splenomegaly
- splenomegaly
- pigment gallstones.
- pigment gallstones.
- ulcers
- ulcers
- aplastic crises ( parvovirus)
- aplastic crises ( parvovirus)
- folate def ( rapid Hb turnover).
- folate def ( rapid Hb turnover).

Hemolytic Anemia
Hemolytic Anemia
Investigations:
Investigations:
- Inc RBC production
- Inc RBC production

*Hi retics & erythroid hyperplastic
*Hi retics & erythroid hyperplastic
bone marrow.
bone marrow.
- Inc RBC breakdown
- Inc RBC breakdown

* indirect hyperbilirubinemia.
* indirect hyperbilirubinemia.
* inc urine urobilinogen.
* inc urine urobilinogen.
* inc stercobilinogen
* inc stercobilinogen
* reduced haptoglobins.
* reduced haptoglobins.

Hemolytic Anemia
Hemolytic Anemia
Investigations cont;
Investigations cont;
- damaged RBC:
- damaged RBC:
*microspherocytes, fragments
*microspherocytes, fragments
*inc fragility.
*inc fragility.
*shortened RBC survival.
*shortened RBC survival.
- autoimmune test:
- autoimmune test:
*Coomb’s test
*Coomb’s test

Hemolytic Anemia
Hemolytic Anemia
Intravascular hemolysis:
Intravascular hemolysis:
- features are;
- features are;
1. hemoglobin emia/ uria
1. hemoglobin emia/ uria
2. hemosiderinuria.
2. hemosiderinuria.
3. methemoglobinemia.
3. methemoglobinemia.
4. red cell fragments.
4. red cell fragments.

Hemolytic Anemia
Hemolytic Anemia
Hereditary spherocytosis:
Hereditary spherocytosis:
AD.
AD.
Spherical RBC.
Spherical RBC.
Defect in spectrin ( membrane protein)
Defect in spectrin ( membrane protein)
Neonatal jaundice- splenomegaly- leg
Neonatal jaundice- splenomegaly- leg
ulcers- aplastic crises- pigment gallstones.
ulcers- aplastic crises- pigment gallstones.
High Retics & osmotic fragility.
High Retics & osmotic fragility.
Splenectomy. Folic acid.
Splenectomy. Folic acid.

Hemolytic Anemia
Hemolytic Anemia
Hereditary elliptocytosis:
Hereditary elliptocytosis:
AD.
AD.
Similar but milder to spherocytosis.
Similar but milder to spherocytosis.
Cells are elliptical.
Cells are elliptical.

Hemolytic Anemia
Hemolytic Anemia
G6PD deficiency:
G6PD deficiency:
X-linked.
X-linked.
Females may be mildly affected.
Females may be mildly affected.
G6PD (hexose- monophosphate Pathway)
G6PD (hexose- monophosphate Pathway)
Defect cause RBC hemolysis with oxidant
Defect cause RBC hemolysis with oxidant
Type A; african type
Type A; african type
-milder, young RBC
-milder, young RBC
 normal Enz activity
normal Enz activity
Type B; mediterranean type
Type B; mediterranean type
- severe, all RBC affected.
- severe, all RBC affected.

Hemolytic Anemia
Hemolytic Anemia
G6PD deficiency cont;
- neonatal jaundice.
- neonatal jaundice.
- hemolytic crises;
- hemolytic crises;
1. sepsis.
1. sepsis.
2. drugs ( antimalarial, septrin, aspirin,
2. drugs ( antimalarial, septrin, aspirin,
sulpaonamides, naphthalene.
sulpaonamides, naphthalene.
3. fava bean. (type B only)
3. fava bean. (type B only)

Hemolytic Anemia
Hemolytic Anemia
Hg normal between attacks.
Hg normal between attacks.
G6PD decreased. May be normal in crises
G6PD decreased. May be normal in crises
In crises: bite cells- blister cells- Heinz
In crises: bite cells- blister cells- Heinz
bodies- high retics- IV hemolysis.
bodies- high retics- IV hemolysis.
Stop causative drug.
Stop causative drug.
High fluid intake.
High fluid intake.
Transfusions as required.
Transfusions as required.

Hemolytic Anemia
Hemolytic Anemia
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia
- autoantibodies.
- autoantibodies.
- warm type;
- warm type;
*IgG. Best temp 37 c.
*IgG. Best temp 37 c.
*causes ( idiopathic- SlE- RhA- CLL-methydopa)
*causes ( idiopathic- SlE- RhA- CLL-methydopa)
* hemolytic anemia- splenomegaly.
* hemolytic anemia- splenomegaly.
* + ve coomb’s- spherocytosis.
* + ve coomb’s- spherocytosis.
* remove the cause- Steroids- splenectomy
* remove the cause- Steroids- splenectomy
immunosupp.- High dose Ig - BT- folate.
immunosupp.- High dose Ig - BT- folate.

Hemolytic Anemia
Hemolytic Anemia
Autoimmune hemolytic anemia cont;
Autoimmune hemolytic anemia cont;
- cold type:
- cold type:
* IgM- optimal temp 4c
* IgM- optimal temp 4c
* idiopathic- EBV- CMV
* idiopathic- EBV- CMV
mycoplasma lymphoma-
mycoplasma lymphoma-
* splenomegaly- acrocyanosis.
* splenomegaly- acrocyanosis.
* +ve coomb’s
* +ve coomb’s
* remove the cause- keep warm.
* remove the cause- keep warm.

Hemolytic Anemia
Hemolytic Anemia
Paroxysmal nocturnal hemoglobinemia
Paroxysmal nocturnal hemoglobinemia
RBC destroyed by complement
RBC destroyed by complement
WBC & Plt may be affected.
WBC & Plt may be affected.
*Hemolysis- dark urine- thrombosis.
*Hemolysis- dark urine- thrombosis.
* Ham’s test +ve( RBC lysis at low pH)
* Ham’s test +ve( RBC lysis at low pH)
* Supportive ttt- consider anticoaggulant.
* Supportive ttt- consider anticoaggulant.
* leukemia- aplastic anemia may develop.
* leukemia- aplastic anemia may develop.

Aplastic Anemia
Aplastic Anemia
Pancytopenia due to bone marrow aplasia.
Pancytopenia due to bone marrow aplasia.
* Primary;
* Primary;
- congenital ( fanconi anemia)
- congenital ( fanconi anemia)
- idiopathic ( 50%).
- idiopathic ( 50%).
* 2
* 2nd
nd
;
;
- drugs ( cytotoxic- chloramphenicol)
- drugs ( cytotoxic- chloramphenicol)
- infection ( viral hepatitis- EBV
- infection ( viral hepatitis- EBV
measles- Tb- parvovirus)
measles- Tb- parvovirus)
- Radiation.
- Radiation.

Aplastic Anemia
Aplastic Anemia
Blood film;
Blood film;
- normochromic normocytic anemia.
- normochromic normocytic anemia.
- leucopenia.
- leucopenia.
- thrombocytopenia.
- thrombocytopenia.
Bone marrow;
Bone marrow;
- trephine biopsy ( hypoplasia with replacement
- trephine biopsy ( hypoplasia with replacement
with fat cell.)
with fat cell.)
Remove the cause- supportive ttt-
Remove the cause- supportive ttt-
Specific ttt:
Specific ttt:
- bone marrow transplant.
- bone marrow transplant.
- Steroid- androgen- cyclosporin- hemopoietic
- Steroid- androgen- cyclosporin- hemopoietic
growth factors- antilymphocyte globulin)
growth factors- antilymphocyte globulin)

Aplastic Anemia
Aplastic Anemia
Fanconi anemia
Fanconi anemia
AR.
AR.
presentation at 5-10 years.
presentation at 5-10 years.
* growth retardation- absent radii/ thumb-
* growth retardation- absent radii/ thumb-
microcephaly- pelvic kidney- mental retard - cafe’-
microcephaly- pelvic kidney- mental retard - cafe’-
au-lait- hypopigment area.
au-lait- hypopigment area.
* chromosomal breakage.( AML risk).
* chromosomal breakage.( AML risk).
* BMT. Androgens.
* BMT. Androgens.
* without BMT they die < 30 yrs.
* without BMT they die < 30 yrs.

Aplastic Anemia
Aplastic Anemia
Red cell aplasia
Red cell aplasia
Isolated anemia due to reduced erthroblasts
Isolated anemia due to reduced erthroblasts
in bone marrow.
in bone marrow.
A. Acute disease; ( transient last 2-3 m)
A. Acute disease; ( transient last 2-3 m)
- infections; parvovirus in
- infections; parvovirus in
hemolytic anemia.
hemolytic anemia.
- viral infections in infants.
- viral infections in infants.
- drugs (septrin- azathio)
- drugs (septrin- azathio)

Aplastic Anemia
Aplastic Anemia
Red cell Aplasia cont;
Red cell Aplasia cont;
B. chronic disease;
B. chronic disease;
* congenital
* congenital 
 Diamond- Blackfan.
Diamond- Blackfan.
* acquired
* acquired
 thymoma, SLE, leukemia
thymoma, SLE, leukemia
idiopathic.
idiopathic.
- supportive- steroid- rarely BMT.
- supportive- steroid- rarely BMT.

Aplastic Anemia
Aplastic Anemia
Diamond- Blackfan syndrome:
Diamond- Blackfan syndrome:
AR.
AR.
Pure RBC aplasia.
Pure RBC aplasia.
Profound anemia at 2-6 months.
Profound anemia at 2-6 months.
Dysmorphic faces- triphalangeal thumb (30%).
Dysmorphic faces- triphalangeal thumb (30%).
Macrocytic anemia- reduced retics.
Macrocytic anemia- reduced retics.
Thrombocytosis & neutropenia initially.
Thrombocytosis & neutropenia initially.
reduced erythrcyte precursors in bone marrow.
reduced erythrcyte precursors in bone marrow.
steroids- transfusions- if no response
steroids- transfusions- if no response

immunosuppression, androgens, BMT.
immunosuppression, androgens, BMT.

Genetic Hg Disorders
Genetic Hg Disorders
Sickle cell Hemoglobinopathies
Sickle cell Hemoglobinopathies
Abnormal Hb synthesis
Abnormal Hb synthesis
HbS = Hb alpha2- (beta2 S)
HbS = Hb alpha2- (beta2 S)
Valine substituted for glutamic acid.
Valine substituted for glutamic acid.
In low PO
In low PO2
2 HbS insoluable
HbS insoluable
 polymerates
polymerates
as long fibres
as long fibres
 RBC sickle shape.
RBC sickle shape.

Sickle cell
Sickle cell
Sickle cells
Sickle cells
 block microcirculation
block microcirculation

microinfarcts.
microinfarcts.
HbS release O
HbS release O2
2 more readily than HbA.
more readily than HbA.
SC anemia: HbSS
SC anemia: HbSS
 85-95%HbS.
85-95%HbS.
5-15%HbF. No HbA.
5-15%HbF. No HbA.
SC trait: HbSA
SC trait: HbSA
 40% HbS, 60% HbA.
40% HbS, 60% HbA.

Sickle cell Anemia
Sickle cell Anemia
HbSS. ( homozygous)
HbSS. ( homozygous)
Africans, Mediterraneans and Indians.
Africans, Mediterraneans and Indians.
*Severe anemia.
*Severe anemia.
*Crises:
*Crises:
1. Painful Crises ( vascular-occlusive)
1. Painful Crises ( vascular-occlusive)
cold, hypoxia, infection, dehydration.
cold, hypoxia, infection, dehydration.
Occurs in bone( commonest).
Occurs in bone( commonest).
Dactylitis ( hand- foot syndrome).
Dactylitis ( hand- foot syndrome).
Sickle chest syndrome.
Sickle chest syndrome.
stroke.
stroke.
Autospenectomy.
Autospenectomy.

Sickle cell Anemia
Sickle cell Anemia
2. Aplastic crises:
2. Aplastic crises:
Sudden fall in Hb & retics.
Sudden fall in Hb & retics.
Parvovirus infection.
Parvovirus infection.
3. Acute sequestration:
3. Acute sequestration:
sickling & pooling of blood in
sickling & pooling of blood in
organs.
organs.
4. Hemolytic crises:
4. Hemolytic crises:
Hemolysis.
Hemolysis.

Sickle cell Anemia
Sickle cell Anemia
* Other:
* Other:
leg ulcer, pigment gallstones, salmonella
leg ulcer, pigment gallstones, salmonella
osteomylitis, Priapism ( pooling of blood in
osteomylitis, Priapism ( pooling of blood in
the corpora cavernosa).
the corpora cavernosa).
Proliferative retinopathy.
Proliferative retinopathy.
Splenomegaly in infancy.
Splenomegaly in infancy.
Autosplectomy in older children.
Autosplectomy in older children.
Blood film
Blood film
 S-cells, target cells, Howell-
S-cells, target cells, Howell-
Jolly bodies.
Jolly bodies.
Hb electrphoresis.
Hb electrphoresis.

Sickle cell Anemia
Sickle cell Anemia
Folic acid.
Folic acid.
Oral penicillin daily.
Oral penicillin daily.
Vaccination
Vaccination
 pneumo- Hib- meningovax
pneumo- Hib- meningovax
Avoid crises.
Avoid crises.
Crises:
Crises:
- analgesics.
- analgesics.
- fluids.
- fluids.
- rest.
- rest.
- transfusions.
- transfusions.
- Ex-BT
- Ex-BT
 severe painful, neurological, sequestratn,
severe painful, neurological, sequestratn,
sickle chest.
sickle chest.

Sickle cell Anemia
Sickle cell Anemia
Surgery;
Surgery;
major surgery
major surgery
 give preoperative BT to
give preoperative BT to
red HbS to < 30%..
red HbS to < 30%..
Anesthetic care( keep warm well
Anesthetic care( keep warm well
oxygenated and hydrated. Avoid acidosis.
oxygenated and hydrated. Avoid acidosis.
New therapies:
New therapies:
1.BMT.
1.BMT.
2. Hydroxyuria.
2. Hydroxyuria.

Sickle cell trait
Sickle cell trait
Heterozygous. HbSA.
Heterozygous. HbSA.
May protect against F. malariae.
May protect against F. malariae.
Benign course with no anemia.
Benign course with no anemia.
Sickling occurs in severe hypoxia.
Sickling occurs in severe hypoxia.
Hematuria.
Hematuria.
Care in GA. & pregnancy.
Care in GA. & pregnancy.
Hb electrophoresis & sickling test.
Hb electrophoresis & sickling test.

Thalassemias
Thalassemias
Total or partial deletn of globin genes.
Total or partial deletn of globin genes.
Reduced rate of synthesis of normal
Reduced rate of synthesis of normal
alpha / beta chains + ppted excess chains
alpha / beta chains + ppted excess chains
in RBC
in RBC 
 causes hemolysis.
causes hemolysis.
a- thalassemia
a- thalassemia
 whole a- globin gene
whole a- globin gene
deleted.
deleted.
b- thalassemia
b- thalassemia
 point mutatn in the gene
point mutatn in the gene

Thalassemias
Thalassemias
b- thal: reduced/ absent b- globin chain
b- thal: reduced/ absent b- globin chain

exess a- chains precipitate.
exess a- chains precipitate.
a- thal: reduced/ absent a globin chains a-
a- thal: reduced/ absent a globin chains a-
globin chains
globin chains 
 exess b- chains
exess b- chains
precipitate.
precipitate.
Chromosome 16
Chromosome 16 
 a- globins.
a- globins.
Chromosome 11
Chromosome 11 
 b, g, d- globins.
b, g, d- globins.

Thalassemias
Thalassemias
Clinical types:
Clinical types:
- a thal
- a thal
- b thal
- b thal
- thal intermedia
- thal intermedia
- thal minor.
- thal minor.

Thalassemias
Thalassemias
Hemoglobin types:
Hemoglobin types:
- Hb A
- Hb A
 a2- b2
a2- b2
- Hb A2
- Hb A2 
 a2 d2
a2 d2
- Hb F
- Hb F 
 a2 g2
a2 g2
- Hb H
- Hb H 
 b4
b4
- Hb Bart g4 ( no O2 carrying ability)
- Hb Bart g4 ( no O2 carrying ability)

Thalassemias
Thalassemias
b- thal major:
b- thal major:
homozygous dis.
homozygous dis.
No b- chains or small amount of b- chains
No b- chains or small amount of b- chains

Thalassemias
Thalassemias
Clinical features
Clinical features
severe anemia from 3- 6 m.
severe anemia from 3- 6 m.
hepatosplenomegaly.
hepatosplenomegaly.
extramed & medullary hemopoiesis;
extramed & medullary hemopoiesis;
thal faces ( frontal bossing- maxillary
thal faces ( frontal bossing- maxillary
hyperplasia.) hair on end skull X-ray. cortical
hyperplasia.) hair on end skull X-ray. cortical
thinning e’ #.
thinning e’ #.
Fe overload.
Fe overload.
Infections
Infections 
 HBV, HCV, HIV.
HBV, HCV, HIV.

Thalassemias
Thalassemias
Blood film:
Blood film:
- microcytic hypochromic anemia, target
- microcytic hypochromic anemia, target
cells, basophilic stippling, nucleated RBCs.
cells, basophilic stippling, nucleated RBCs.
Hb electrophoresis:
Hb electrophoresis:
- HbF 70-90%
- HbF 70-90%
- Hb A2 2%
- Hb A2 2%
- Hb A 0-20%
- Hb A 0-20%
DNA analysis.
DNA analysis.

Thalassemias
Thalassemias
Management:
Management:
- Blood transfusions 4- 6 wkly.
- Blood transfusions 4- 6 wkly.
- Folic acid.
- Folic acid.
- Fe chelation; s.c. desferrioxamine.
- Fe chelation; s.c. desferrioxamine.
( assess hearing & vision )
( assess hearing & vision )
- Vit C 200 mg / d.
- Vit C 200 mg / d.
- splenectomy done > 6 yrs.
- splenectomy done > 6 yrs.
- BMT.
- BMT.

Thalassemias
Thalassemias
Fe overload;
Fe overload;
- liver cirrhosis, hepatoma.
- liver cirrhosis, hepatoma.
- heart- cardiomyopathy.
- heart- cardiomyopathy.
- endocrine- IDDM, growth failure,
- endocrine- IDDM, growth failure,
delayed puberty, hypothyroidism,
delayed puberty, hypothyroidism,
hypoparathyroidism, osteoporosis.
hypoparathyroidism, osteoporosis.
- skin- slate grey appearance.
- skin- slate grey appearance.

Thalassemias
Thalassemias
Thal minor ( trait) :
Thal minor ( trait) :
- hetrozygous dis with reduced b- chains.
- hetrozygous dis with reduced b- chains.
- asymptomatic.
- asymptomatic.
- mild or no anemia.
- mild or no anemia.
- microcytic/ hypochromic, target cells
- microcytic/ hypochromic, target cells
- Hb electrophoresis Hb A
- Hb electrophoresis Hb A
Hb A2 > 3.5 %
Hb A2 > 3.5 %
Hb F increased.
Hb F increased.

Polycythemia
Polycythemia
Increased Hb & Hct above normal.
Increased Hb & Hct above normal.
- Causes;
- Causes;
* Iry ; Polycythemia rubra vera (PV).
* Iry ; Polycythemia rubra vera (PV).
* 2
* 2nd
nd
; cynotic heart dis, lung dis, high
; cynotic heart dis, lung dis, high
altitude, central hypoventilation.
altitude, central hypoventilation.
renal ( hydronephrosis- tumor,
renal ( hydronephrosis- tumor,
cyst) adrenal ( CAH- Cushing synd)
cyst) adrenal ( CAH- Cushing synd)
tumor ( HCC- cerebellar hemangioblastoma)
tumor ( HCC- cerebellar hemangioblastoma)

Polycythemia
Polycythemia
Clinical features:
Clinical features:
- hemorrhage.
- hemorrhage.
- thrombosis.
- thrombosis.
- headaches.
- headaches.
Treat the cause.
Treat the cause.
Venesection if needed.
Venesection if needed.
Chemotherapy for PV
Chemotherapy for PV

Thrombocythemia
Thrombocythemia
Increased platelets count.
Increased platelets count.
causes;
causes;
endogenous
endogenous
 essential
essential
thrombocythemia, CML, PV.
thrombocythemia, CML, PV.
reactive
reactive
 hage, postoperative,
hage, postoperative,
kawasaki dis, chronic infections,
kawasaki dis, chronic infections,
connective tissue dis, post splenectomy,
connective tissue dis, post splenectomy,
Fe deficiency, hemolytic anemia.
Fe deficiency, hemolytic anemia.
Asymptomatic. Risk of thrombosis is rare.
Asymptomatic. Risk of thrombosis is rare.

Polycythemia
Polycythemia
Management:
Management:
- no ttt.
- no ttt.
- to reduce risk of thrombosis platelet
- to reduce risk of thrombosis platelet
pheresis- low dose Aspirin- or anagrelide
pheresis- low dose Aspirin- or anagrelide
- cytotoxic or a- interferon for PV and
- cytotoxic or a- interferon for PV and
essential thrombocythemia.
essential thrombocythemia.

Haemostasis
Haemostasis
Hemostasis involves
Hemostasis involves
1- normal vasculature.
1- normal vasculature.
2- platelets.( lifespan 7-10 d). Produced
2- platelets.( lifespan 7-10 d). Produced
in bone marrow from megakaryocytes. It
in bone marrow from megakaryocytes. It
function in plug formation.
function in plug formation.
3- coagulation factors.
3- coagulation factors.
a cascade activates these factors
a cascade activates these factors

thrombin & fibrin clot. Fibrin stabilizes the
thrombin & fibrin clot. Fibrin stabilizes the
platelet plug.
platelet plug.

Vascular disorders
Vascular disorders
Abnormality in vessels/ perivascular CT.
Abnormality in vessels/ perivascular CT.
Causes:
Causes:
- inhereted
- inhereted
 H. hegic telangiectasia.
H. hegic telangiectasia.
- acquired
- acquired
 HSP, meningitis, scurvy, steriods
HSP, meningitis, scurvy, steriods
and CT dis ( Ehlers- Danlos)
and CT dis ( Ehlers- Danlos)
Clinical features:
Clinical features:
- usually not severe.
- usually not severe.
- skin & mucous membrane bleeding.
- skin & mucous membrane bleeding.
Screening tests normal ( including bleeding
Screening tests normal ( including bleeding
time).
time).

Platelet disorders
Platelet disorders
Thrombocytopenia:
Thrombocytopenia:
causes:
causes:
1. decreased production;
1. decreased production;
- infection
- infection
- TAR
- TAR
- drugs syndrome.
- drugs syndrome.
- Wiskott- Aldrich syndrome.
- Wiskott- Aldrich syndrome.
- aplastic anemia.
- aplastic anemia.

Platelet disorders
Platelet disorders
Increased consumption:
Increased consumption:
- ITP
- ITP
- drug induced (quinine, trimethoprim).
- drug induced (quinine, trimethoprim).
- post-infection ( malaria).
- post-infection ( malaria).
- neonatal isoimmune.
- neonatal isoimmune.
- SLE, heparin.
- SLE, heparin.
- post-transfusion.
- post-transfusion.
- DIC, TTP, HUS.
- DIC, TTP, HUS.
Abnormal distribution:
Abnormal distribution:
- splenomegaly.
- splenomegaly.

Idiopathic thrombcytopenic purpura
( ITP )
( ITP )
Common in children.
Common in children.
Immune complex ?
Immune complex ?
Post infection ( VZV, EBV, measles)
Post infection ( VZV, EBV, measles)
1-4 wks post-infection
1-4 wks post-infection

- bleeding, bruising, purpura, petechiae
- bleeding, bruising, purpura, petechiae
- low platelets.
- low platelets.
- normal Hb & WBC
- normal Hb & WBC
- high or normal megakaryocytes in BM.
- high or normal megakaryocytes in BM.
- Antiplatelets IgG, IgM
- Antiplatelets IgG, IgM

( ITP )
( ITP )
ttt options:
ttt options:
- monitoring only.
- monitoring only.
- steroids.
- steroids.
- IVIG
- IVIG
- Plts transfusions ( in emergency)
- Plts transfusions ( in emergency)
- immunosuppresion / splenectomy in
- immunosuppresion / splenectomy in
chronic disease.
chronic disease.
most cases resolve spontaneouly
most cases resolve spontaneouly
chronic disease ( 5- 10 %). Common in adult.
chronic disease ( 5- 10 %). Common in adult.

Platelet function disorder
Hereditary:
Hereditary:
- Glanzman disease.
- Glanzman disease.
- Bernard- Soulier syndrome.
- Bernard- Soulier syndrome.
Aquired:
Aquired:
- Aspirin ( cyclo- oxygenase inh)
- Aspirin ( cyclo- oxygenase inh)
- heparin ( inh segregatn & secretn)
- heparin ( inh segregatn & secretn)
- uremia
- uremia
- myloproliferative disorders.
- myloproliferative disorders.

- normal plt count.
- normal plt count.
- prolonged bleeding time.
- prolonged bleeding time.
- specific tests
- specific tests
* plt aggregatn ( ADP, ristocetin,
* plt aggregatn ( ADP, ristocetin,
adrenaline, collagen)
adrenaline, collagen)
* adhesion studies.
* adhesion studies.
* von willbrand factor assay.
* von willbrand factor assay.
* factor viii assay.
* factor viii assay.

Clotting factor disorders
Clotting factor disorders
Hemophilia A
Hemophilia A
- X-linked recessive.
- X-linked recessive.
- absent or low factor viii.
- absent or low factor viii.
- spontaneous bleeding:
- spontaneous bleeding:
 joints; hemarthrosis
joints; hemarthrosis
 muscles hematoma
muscles hematoma
 bone pseudtumor.
bone pseudtumor.
 hematuria
hematuria
 intracerebral bleed ( rare)
intracerebral bleed ( rare)

Hemophilia A
Hemophilia A
Excessive traumatic bleeding
Excessive traumatic bleeding
Transfusion related infections;
Transfusion related infections;
( HIV, HBV, HCV)
( HIV, HBV, HCV)
Severity:
Severity:
 - <1%
- <1%
 severe dis
severe dis
 spont bleeding.
spont bleeding.
 - 1-5%
- 1-5%
 severe dis e’ injury
severe dis e’ injury
 - >5%
- >5%
 mild dis.
mild dis.

Hemophilia A
Hemophilia A
Investigations:
Investigations:
1. Factor viii assay.
1. Factor viii assay.
2. Prolonged PTT
2. Prolonged PTT

Hemophilia A
Hemophilia A
Management:
Management:
1. factor viii
1. factor viii
transfusions.
transfusions.
( therapeutic,
( therapeutic,
prophylactic)
prophylactic)
injury
injury
F 8 % of N
F 8 % of N
Minor
Minor
bleed
bleed
> 30%
> 30%
Severe
Severe
bleed
bleed
>50%
>50%
Pre major
Pre major
surgery
surgery
100%
100%

Hemophilia A
Hemophilia A
2. DDAVP ( desmopressin)
2. DDAVP ( desmopressin)
* iv or inhaled
* iv or inhaled 
 inc factor viii.
inc factor viii.
3. Fibrinolytic inhibitors
3. Fibrinolytic inhibitors
* tranexamic acid.
* tranexamic acid.
4. Advice: sport, oral hygiene.
4. Advice: sport, oral hygiene.
Factor viii Antibodies
Factor viii Antibodies:
:
in 10 % . Management;
in 10 % . Management;
- give large doses of factor viii.
- give large doses of factor viii.
- immunosuppression.
- immunosuppression.
- factor ix.
- factor ix.
- recombinant factor viii.
- recombinant factor viii.

Hemophilia B
Hemophilia B
( Christmas disease)
( Christmas disease)
1 in 30,000.
1 in 30,000.
X-linked recessive.
X-linked recessive.
def of factor ix
def of factor ix
clinically identical to hemophilia A.
clinically identical to hemophilia A.
ttt e’ factor ix.
ttt e’ factor ix.

Von Willbrand disease
AD. Variable expression. Worse in female.
AD. Variable expression. Worse in female.
v
vWF is the carrier protein for factor viii.
WF is the carrier protein for factor viii.
v
vWF
WF 
 promotes plt adhesion.
promotes plt adhesion.
Low
Low v
vWF
WF 
 low factor viii activity.
low factor viii activity.
plt adhesion abnormality.
plt adhesion abnormality.
Excessive beeding ( cut, menorrhagia,
Excessive beeding ( cut, menorrhagia,
epistaxis).
epistaxis).
Spontaneous bleeding is rare.
Spontaneous bleeding is rare.

Prolonged bleeding time.
Prolonged bleeding time.
Low factor viii
Low factor viiic
c activity.
activity.
Low vWF level.
Low vWF level.
Low reduced plt aggregation e’ ristocetin.
Low reduced plt aggregation e’ ristocetin.
Treat e’
Treat e’
 factor viii concentrate contain vWF.
factor viii concentrate contain vWF.
 DDAVP.
DDAVP.
 fibrinolytic inhibitors.
fibrinolytic inhibitors.

Vitamin K Deficiency
Fat soluble vit. In green vegetable.
Fat soluble vit. In green vegetable.
Synthesized in the gut.
Synthesized in the gut.
Vit K dependent factors ( II, VII, IX, X).
Vit K dependent factors ( II, VII, IX, X).
Causes:
Causes:
 low stores ( HDN, poor diet)
low stores ( HDN, poor diet)
 malabsorptn ( liver dis, small bowel dis)
malabsorptn ( liver dis, small bowel dis)
 vit K antagonist ( warfarin)
vit K antagonist ( warfarin)

Investigations:
Investigations:
 PT.
PT.
 or N PTT.
or N PTT.
 Management:
Management:
 - iv vit K takes 6 hours to work.
- iv vit K takes 6 hours to work.
 - im / PO
- im / PO 
 prophylaxis.
prophylaxis.
 - FFP
- FFP 
 immediate action.
immediate action.
 - Prothrombin concentrate
- Prothrombin concentrate
 immediate.
immediate.

Best answer
Best answer
All of the followings are true about Fanconi
All of the followings are true about Fanconi
anemia EXCEPT:
anemia EXCEPT:
A. AR
A. AR
B. stable chromosomes.
B. stable chromosomes.
C. median survival 30 yrs.
C. median survival 30 yrs.
D. Increased risk to leukemia.
D. Increased risk to leukemia.
E. aplastic anemia in > 90% of cases.
E. aplastic anemia in > 90% of cases.
Answer: B.
Answer: B.

Best answer
Best answer
Indication of plt transfusion in infants < 4 m
Indication of plt transfusion in infants < 4 m
include all of the following plt count & clinical
include all of the following plt count & clinical
situations EXCEPT:
situations EXCEPT:
A.
A. <100 & bleeding.
<100 & bleeding.
B.
B. < 50 & invasive procedure.
< 50 & invasive procedure.
C.
C. < 20 & stable.
< 20 & stable.
D.
D. < 50 & immune mediated.
< 50 & immune mediated.
E.
E. < 100 & unstable.
< 100 & unstable.
Answer: D
Answer: D

Best answer
Best answer
The bleeding time is the test for:
The bleeding time is the test for:
A.
A. fibrinogen.
fibrinogen.
B.
B. Antithrombin III activity.
Antithrombin III activity.
C.
C. Plt function.
Plt function.
D.
D. Factor viii coagulation activity.
Factor viii coagulation activity.
E.
E. Lupus type anticoagulant.
Lupus type anticoagulant.
Answer: C
Answer: C

Best answer
Best answer
Elevated serum transferrin receptor
Elevated serum transferrin receptor
levels signify:
levels signify:
A.
A. Fe def anemia.
Fe def anemia.
B.
B. Ferritinemia.
Ferritinemia.
C.
C. Acute phase response.
Acute phase response.
D.
D. Aplastic anemia.
Aplastic anemia.
E.
E. Hage.
Hage.
Answer: A
Answer: A

Best answer
Best answer
A 3 m old found to have SCD ( Hb SS)
A 3 m old found to have SCD ( Hb SS)
appropriate measure of ttt should include
appropriate measure of ttt should include
which of the followings:
which of the followings:
A.
A. Prophylactic oral Penicillin Bid.
Prophylactic oral Penicillin Bid.
B.
B. ,, BT every month.
,, BT every month.
C.
C. Monthly desferroxamine ttt to avoid fe
Monthly desferroxamine ttt to avoid fe
overload.
overload.
D.
D. Splenectomy.
Splenectomy.
E.
E. None of the above.
None of the above.
Answer: A.
Answer: A.

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