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C.B.C
MCV - PCV/RBC 85 8 fl
RBC x 3 = HB x 3 = PCV
Normal
Range
5 million
15 g%
4 to 5.7
12 to 17
C. Hematocrit (PCV)
45%
38 to 50
Normal
Range
A.
RCC
5 million
4 to 5.7
B.
Hemoglobin
15 g%
12 to 17
45 %
38 to 50
C. Hematocrit
MCV
MCH
MCHC (%)
C A x 10
B A x 10
B C x 100
=
=
=
90 fl
30 pg
33%
Bone Marrow
Epo
mRNA
Epo
Multi-potent
stem cell
Erythroid
stem cell
Oxygen
sensor
3-4
days
Blood vessel
Peripheral blood
RBC survival
100-120 days
Steps in Erythropoisis
Early
Proerythroblast
(Pronormoblast)
Intermediate
Polychromatophilic
Normoblast
Basophilic
Normoblast
Late
Reticulocyte
Orthochromatophilic
Normoblast
Erythrocyte
Polycythemia
Anemias
An (without) -emia (blood):
Reduction below normal in hemoglobin or red blood
cell number (for age & sex).
Hemoglobin (g/dL)
Male
13-17
(152)
Female
12-15
(13.5 1.5)
Anemias
2,3 DPG
Anemia
HYPOXIA
REDISTRIBUTION
COMPENSATORY
MECHANISMS
C.O.
PATHOPHYSIOLOGY
OF ANEMAIS
PLASMA
Anemias
TIREDNESS
LASSITUDE
EASY
FATIGUABILITY
CNS
MUSCLE
WEAKNESS
GIS
CLINICAL FEATURES
CRS
PALLOR
GUS
Anemias
Classification
Etiological
Morphological
Anemias
ETIOLOGIC
Classification
I
II
IMPAIRED
RED CELL
FORMATION
(Erythropoiesis)
(Dyshaemopoietic)
BLOOD LOSS
(Haemorrhagic)
III
INCREASED
RED CELL
DESTRUCTION
(Haemolytic)
Anemias
ETIOLOGIC
Classification
ACUTE
II
IMPAIRED
RED CELL
FORMATION
DEFICIENCY
NON
DEFICIENCY
CHRONIC
BLOOD
LOSS
III
HEMOLYTIC
ANEMIAS
RBC
ABNORMALITIES
RBC ENVIRONMENT
ABNORMALITIES
DEFICIENCY ANEMIAS
ANEMIAS DUE TO DEFICIENCY OF SUBSTANCES
ESSENTIAL FOR ERYTHROPOIESIS
IRON
DEFICIENCY
ANEMAIS
SUBSTANCES
ESSENTIAL FOR ERYTHROPOIESIS
ACD
ANEMIA
OF
BONE MARROW
INFILTRATION
ANEMIA OF
CHRONIC
DISORDERS
(myelophthisic)
INFECTION COLLAGEN DISEASES,
RENAL FAILURE, LIVER FAILURE,
MALIGNANCY
APLASTIC
ANEMIA
LEUKEMIAS,LYMPHOMAS
MYELOMA,MYELOFIBROSI
S
OTHERS
OTHER
NON DEFICIENCY ANEMIAS
SIDEROBLASTIC
ANEMIAS
CONGENITAL
DYSERYTHROPOITC
ANEMIAS
Anemias
II
MICROCYTIC
HYPOCHROMIC
Iron Deficiency
Thalassemias
MORPHOLOGIC
Classification
I
NORMOCYTIC
NORMOCHROMIC
ACD
III
MACROCYTIC
ANEMIAS
Megaloblastic
Iron metabolism
Iron stores
Laboratory findings of iron deficiency
Causes of iron deficiency
Treatment
Duodenum
(average, 1 - 2 mg
per day)
Dietary iron
Utilization
Plasma
transferrin
(3 mg)
Muscle
(myoglobin)
(300 mg)
Circulating
erythrocytes
(hemoglobin)
(1,800 mg)
Storage
iron
(Ferritin)
Liver
(1,000 mg)
(TIBC)
Iron loss
Bone
marrow
(300 mg)
Reticuloendothelial
macrophages
(600 mg)
1800-2500 mg
300-500 mg
Storage
Iron storage
0-1000 mg
Transit
Serum iron
Total
3 mg
3000-4000 mg
Blood loss
Gastrointestinal tract
Genitourinary tract
Blood donation
Worm infestation
IDA- Pathogenesis
Decreased Iron stores
Decreased Hb Synthesis
Delayed maturation of erythroblasts (cytoplasmic)
Decreased cytoplasm, more division (microcytes)
Decreased Hb content (hypochromia)
Anemia
Pica (pagophagia)
Angular stomatitis
Glossitis
Koilonychia
Ferritin
BM iron
S. Fe/TIBC
Anemia
Depleted stores
Low
Absent
Normal
Absent
Compromised delivery
Low
Absent
Low/High
Absent
Low
Absent
Low/High
Present
Smear
Microcytic / Hypochromic RBCs,
Anisocytosis, Poikilocytosis
Iron deficiency
Thalassemia
Lead toxicity
Sideroblastic anemia
Anemia of chronic disease
Macrocytic Anaemias
Defition:- Anaemias with MCV >95 fl
Classification:A. Megalo-blastic
B. Non-megalo-blastic
Macrocytic Anemia
(with Low Reticulocyte Count)
Megaloblastic anemia
Vitamin B12 deficiency
Folate deficiency
Liver disease
Hypothyroidism
Drug-induced (DNA synthesis block)
Myelodysplastic syndrome
Megaloblastic anemia
Vitamin B12/Folic acid deficiency
Second most common type of anemia.
Multi System disease All organs with increased cell division.
Macrocytic anemia, pancytopenia.
Nurological manifestations in Vitamin B12 deficiency
(demyelination of the posterior and lateral columns of the spinal cord peripheral nerves)
Source
Body stores
Daily requirement
Daily intake
Dietary deficiency
Vitamin B12
(Cobalamin)
Folate
Animal products
5 mg
2-5 g
10-20 g
Rare
Widespread
5 mg
50-200 g
400-800 g
Common
Homocysteine
Methionine
CH3-Cobalamin
Cobalamin
THF
THF-CH3
MMA-CoA
mutase
Succinyl-CoA
Cobalamin
Folate Deficiency
Methylmalonic acid
Increased
Normal
Homocysteine
Increased
Increased
Food-Cbl
H + Peptic
digestion
Cbl + R-binder
R-Cbl
Duodenum
Pancreatic
enzymes R-Cbl
IF + Cb OH -
Cbl-TC complex
Cbl-IF
Distal ileum
Cbl-IF
IF receptor
Cbl + TC
Megaloblastic AnemiaPathogenesis
Decreased Vit B12 / Folate
Decreased DNA Synthesis
Delayed maturation of erythroblasts (Nucleus)
Increased cell size (macrocytes)
Normal Hb content (Normochromia)
Decreased RBC number & Decreased WBC number (pancytopenia)
Anemia & Pancytopenia.
Pernicious Anemia
Most common cause of vitamin B12 deficiency
Occurs in all ages and ethnic backgrounds
Autoimmune destruction of gastric mucosa chronic Atrophic gastritis IF
Associated with other autoimmune diseases
Screen for thyroid disease every 1-2 years
Schilling test
Cobalamin
Cobalamin + IF
Interpretation
Normal
Normal
Dietary insufficiency
Abnormal
Normal
Abnormal
Abnormal
Folate Deficiency
Prevalence
20-95%
Autoimmune disease
8-17%
Cancer
Chronic solid organ rejection
Characteristics
30-77%
8-70%
Decreased RBC
precursors
Inadequate Epo
response
Blocked in
Anemia of chronic disease
Treatment with
IVIG
Clinical setting
Immunocompetent patients with chronic hemolysis
Immunodeficient patients with persistent viremia
Aplastic Anemia
Suppression of multipotent myeloid stem cells
Anemia, thrombocytopenia, neutropenia
Etiology: idiopathic (65%), irradiation, myelotoxic drugs,
chemicals, viruses (viral hepatitis)
Idiosyncratic reaction: chloramphenicol, sulfonamides
BM: hypocellular with fat replacement (>90%)
No splenomegaly, if + diagnosis, not AA
No reticulocytosis
Treatment: stop drug, BMT (< 40 y/o) for idiopathic,
immunosuppression for older patients, w/o donors
Aplastic anemia
HEMOLYTIC ANEMIA
Acquired
Immune mediated
Autoimmune hemolytic anemia
Nonimmune mediated
Spur cell hemolytic anemia
Target cell
Sickle cells
Anisocytosis/poikilocytosis
Vaso-occlusive complications
Diagnosis:
-Peripheral smear, Lab iron studies & Electrophoresis
Treatment:
Hydroxyurea
Increases HbF = retards sickling by inhibiting
polymer formation
RBC transfusions
RBC exchanges during acute crises
Hereditary Spherocytosis
Abnormal RBC skeletal/membrane proteins (ie. Ankyrin)
RBCs with reduced membrane stability lose membrane
fragments, assume a sphere
Clinical: anemia, splenomegaly, jaundice
Lab: osmotic fragility
Upon exposure to hypotonic salt solution, spheroidal
shape limits volume of expansion.
RBCs shortened lifespan
Treatment: splenectomy to alleviate anemia, continue to
have spherocytes
Hereditary Spherocytosis
Glucose-6-Phosphate
Dehydrogenase Deficiency
Sex-linked disorder
Effects > 200 million people
Hemolytic anemia occurs in the presence of stress (infection or
drugs- antimalarial, sulphonamide, nitrofurantoin etc)
Lymphoproliferative disease
Connective tissue disease
Infectious disease
Drug-induced (aldomet, PCN, Quinidine)
Cold antibody:
M. pneumoniae. Infectious mononucleosis
Laboratory testing
Normocytic/macrocytic anemia
+ DAT detects anti-RBC antibodies
Peripheral smear - spherocytosis
45%
40%
15%
+
Patients RBCs
Anti-C3d
Anti-IgG
+
Patients serum RBCs
+
Anti-IgG
Thalassemia
NORMAL INDIVIDUAL
4 -globin genes
on chromosomes No 16
( 2 on each chromosome)
2 from the father
& 2 from the mother
2 - globin genes
on chromosomes No 11
( 1 on each chromosome)
1 from the father
& 1 from the mother
Net result :-
Normal Hemoglobin(s)
22
Hb%
2 2
A2
Adult
In ant
F
1
A2
1.6 - 3.2
A
97
22
Gower 1
22
Portland
22
Gower II
22
22
A2
22
cluster - chromosome 11
Hg a d u
b lt
of
cluster - chromosome 16
De
ve
l
pe opm
rio en
d
t
Gl
o
co bin
mp ch
on ain
en
t
Hg
bn
am
e
Embryonic
Fetal
< 1%
1.5-3.5%
Adult
A
> 95%
Thalassemia
Decreased production of normal globin chains
thalassemia- deficiency of genes (mostly deletions)
thalassemia- deficiency of genes (mostly mutations)
Thalassemia
Heterozygote thalassemia
thalassemia
Europe 4-12%
Middle East and western Asia - 12-55%
Southeast Asia 6-75%
Africa 11-50%
South America and the Caribbean - 7%
Father
/
Normal
Mother
-Thalassemia(s)
-/
--/
-/-
Silent carrier
- thal minor
(-thal trait)
--/-
--/--
HbH disease
Hb. Barts
Hydrops fetalis
X
XX
XX
XX
XX
X
X
MCV (fl)
Analysis
Normal
Normal
Normal
/-
12-14
75-85
Normal
-/- or
--/
11-13
70-75
--/-
7-10
50-60
--/--
Not viable
- Thalassemia(s)
thalassemia
major
thalassemia
minor
Beta Thalassemia
Clinical
Syndrome
Genotype
Hgb (g/dl)
Hgb
Analysis
Minor (Trait)
/+ or /
Intermedia
+/+
7-10
Major (Cooleys)
+/ or /
<7
10-13
thalassemia intermedia/major
Screening/counseling
RBC transfusion therapy (+ chelation therapy)
Agents to increase hemoglobin F (hydroxyurea)
Bone marrow transplantation
Smear
Microcytic / Hypochromic RBCs,
Anisocytosis, Poikilocytosis, target
cells
Thalassemia
Hemolytic Anemia
RBC destruction
erythropoiesis:
reticulocytosis
Iron accumulation:
hemosiderosis
Etiology:
Intravascular: heat,
clostridia toxin, trauma
complement fixation
Extravascular (RES)
Intravascular:
hemoglobinemia,
hemoglobinuria,
hemosiderinuria
haptoglobin
Extravascular
No hemoglobinemia or
hemoglobinuria
Normal haptoglobin
Microspherocytes
Differential diagnosis
of Anemia
Low Hb=Anemia
MCV
Low
microcytic
Normal
normocytic
High
macrocytic
Measure Ferritin
Low
Iron def anemia
Normal/high
Normal
Anemia of
chronic disease
Congenital Hb dis.
Low
Megaloblastic anemia
Reticulocyte count
Hemolytic anemia or
blood loss
high
low
Normal
Hypercellular
Hypocellular