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BACK
TO
PATH
II
TUTORING!!!!
J
Chris
Hal3gin
Wafa
Khadraoui
Isael
Perez
Anemia
• S/S:
– Fa3gue,
headache,
dyspnea
– PALLOR!!!!
of
conjunc3va,
tongue,
nail
beds,
palms
– Mild
murmur
due
to
hypoviscosity
– Cardiomegaly
from
increased
O2
demand
by
3ssues
• Decreased
Hb
and
HCT!!!!
• Classified
based
on
RBC
indices:
– MCV
=
RBC
size
• Microcy3c,
Normocy3c,
Macrocy3c
– MCHC
=
Hb
content
• Hypochromic,
Normochromic,
Hyperchromic
• Area
of
central
pallor
is
normally
1/3
of
the
diameter
of
the
RBC
– ReHculocye
count
• Increased
(aka
Polychromasia)
=
marrow
response
to
premature
blood
loss
or
increased
destruc3on
of
RBCs
(hemoly3c
anemia)
• Normal
or
Low
=
Anemias
of
underproduc3on
– RDW
=
uniformity
of
size
and
shape
of
RBCs
Morphologic Classification of Anemia
Chronic disease
Aplastic anemia
Renal failure
Mild hemolytic
anemia B12/folate deficiency
Iron deficiency Drugs, Liver disease
Anemia
of
chronic
Sideroblastic disease
is
most
Hypothyroidism
Thalassemia trait commonly
Normocy3c
Hemolytic anemia
Chronic disease Hemorrhage
Functional Classification of Anemia
Low/Normal High
Reticulocyte Reticulocyte
Hemolytic
Nutrition Marrow Ineffective Lack of anemia
Deficiency Suppres utilization EPO
Hemorrhage
-Fe -Aplastic Anemia of Renal
-B12 -MDS chronic Failure
disease
-Folate -Drugs
-Malignancy Sideroblastic
Microcytic Normocytic MCV 80-96 Macrocytic
MCV <80 MCV >98
Low/normal retic
retic
– B-‐thal.
Minor
• Usually
asymptoma3c
• Peripheral
smear
may
show
microcy3c
hypochromic
RBCs,
with
basophilic
s3ppling
or
target
cells
• Increased
HbA2
(which
differen3ates
it
from
iron
deficiency)
– B-‐thal.
Major
• IneffecHve
hematopoiesis
due
to
aggregates
of
unpaired
a-‐globin
chainsà
a4
tetramersà
severe
extravascular
hemolysis
• No
HbA,
Increased
HbF,
and
increased
HbA2
• Crew
Cut
appearance
• Progressive
iron
overload,
secondary
hemochromatosis,
and
cardiac
disease
Anemia
of
Increased
Destruc3on
• Paroxysmal
Nocturnal
Hemoglobinuria
– NormocyHc
normochromic
– ACQUIRED
PIGA
gene
mutaHon
that
causes
loss
of
the
GPI
anchoring
protein
(regulatory
complement
protein)
in
stem
cellsà
complement-‐mediated
intravascular
hemolysis
by
the
MAC
– Deficient
GPIs
=
CD55
(DAF)
and
CD59
(inhibits
C3
convertase
and
prevents
ac3va3on
of
alterna3ce
pathway)à
increased
C3
convertase
acHvity
• RBC
lysis
occurs
at
night
because
when
we
sleep
our
pH
decreases,
which
makes
complement
more
ac3ve
– GPI
defect
in
hematopoie3c
stem
cellsà
deficiency
of
GPI
on
RBCs,
WBCs,
and
plateletsà
Pancytopenia
– Increased
risk
of
venous
thrombosis,
especially
portal,
cerebral,
and
hepa3c
veins
– Red
urine
IN
MORNING,
hemoglobinemia,
hemoglobinuria,
hemosidiuria
– Increased
reHculocytes,
decreased
Haptoglobin
– Associated
with
aplas3c
anemia,
AML,
and
myelodysplas3c
syndrome
– Increased
sensi3vity
to
complement
RBC
lysis
in
Sucrose
lysis
or
Ham
test
– Tx
=
HSC
transplanta3on
Anemia
of
Increased
Destruc3on
• Autoimmune
hemolyHc
anemias
– NormocyHc
normochromic
– Warm
Ab
• IgG,
37oC,
extravascular
hemolysis
from
IgG
RBC
opsonizaHon
• Opsoniza3on
of
RBCs
by
IgG
causes
par3al
phagocytosis
of
RBC
membraneà
generaHon
of
spherocytesà
sequestra3on
and
destruc3on
by
spleenà
SPELENOMEGALY
• Primaryà
Idiopathic
• Secondaryà
SLE,
Drugs
(penicillin,
cephalosporins,
an3malarials,
methyldopa),
CLL
• Peripheral
smear
looks
like
hereditary
spherocytosis,
so
pay
ajenHon
to
the
paHents
age
and
presentaHon…
HS
pa3ent
will
be
younger!!!!
– Cold
AggluHnin
• IgM,
<37oC,
usually
0oC-‐4oC,
intravascular
hemolysis
from
IgM
acHvaHon
of
complementà
clumping
of
RBCs
• Acuteà
post-‐infec3on
(Mycoplasma
pneumoniae,
infec3ous
mononucleosis)
• Chronicà
idiopathic,
lymphoid
neoplasms
• Associated
with
Raynaud’s
phenomena
in
the
digits
when
they
are
exposed
to
cold
temperatures
– Cold
Hemolysin
• IgG
to
P-‐group
Ag,
<37oC,
intravascular
hemolysis,
Children,
aRer
viral
infecHons
Non-‐immune
Hemoly3c
Anemias
• Mechanical
arHficial
heart
valves
• Malignany
HTN
SCHISTOCYTES!!!!
• MAHAs
– DIC
• Elevated
D-‐dimer,
increased
PT
and
PTT
• Massive
ac3va3on
of
coagula3on
cascadeà
consump3on
of
coagula3on
factorsà
systemic
microthrombi
– TTP
• ADAMTS13
muta3on
• Fever,
neurological
symptoms,
renal
failure,
TCP,
hemoly3c
anemia
• Normal
PT
and
PTT
– HUS
• E.coli
O157:H7
• Fever,
no
neurological
symptoms,
profound
renal
failure,
TCP,
hemoly3c
anemia
• Normal
PT
and
PTT
Anemia
of
Decreased
Produc3on
• MegaloblasHc
Anemia
– MacrocyHc
normochromic
– B12
or
Folate
deficiencyà
impaired
DNA
synthesisà
ineffec3ve
hematopoiesis
and
abnormally
large
erythroid
precursors
and
RBCs
• Folate
deficiencyà
ALCOHOLIC,
pregnancy
(hopefully
not!!!!),
drugs
(Methotrexate),
hemodialysis
– No
neurological
problems,
normal
methylmalonic
acid,
increased
homocysteine
• B12
deficiencyà
Pernicious
anemia
(due
to
autoimmune
gastri3s
an3-‐IF
or
an3-‐parietal
cell
Abs),
Crohn
disease,
gastrectomy,
ileal
resec3on,
the
good
old
fish
tapeworm
diphylobothrium
latum,
strict
vegans
– Neurological
problems,
increased
methylmalonic
acid,
increased
homocysteine
– DemyelinaHon
of
dorsal
and
lateral
spinal
tractsà
subacute
combined
neurological
degeneraHonà
Hngling,
loss
of
touch,
vibraHon,
propriocepHon,
depressed
reflexes,
ataxia
– Macroovalocytes,
HYPERSEGMENTED
NEUTROPHILS
>5
lobes,
decreased
to
normal
reHculocytes
– Hypercellular
bone
marrow
due
to
increased
hematopoe3c
precursors
and
megaloblasHc
erythroid
hyperplasiaà
crowding
of
bone
marrowà
slower
producHon
of
RBCsà
anemia
– Atrophic
glossiHs
Decreased Production
Anemia
of
Decreased
Produc3on
Peripheral smear
Iron deficiency anemia
Peripheral smear
• SideroblasHc
anemia
– MicrocyHc
hypochromic
– Heme
(porphyrin)
synthesis
defect
in
mitochondria
and
failure
of
iron
uHlizaHon
– Hereditaryà
ALAS
gene
deficiency
XR
– Acquiredà
ALCOHOL,
drugs,
B6
deficiency,
Lead
poisoning,
MDS
– May
also
be
idiopathic
Basophilic
s3ppling
Ringed
– Normocellular
bone
marrow
with
increased
iron
Basophilic
Sideroblast
stores
stippling
Ringed
sideroblasts
– Increased
RDW,
Basophilic
sHppling,
Ringed
sideroblasts
(mitochondrial
iron
overload)
– Increased
serum
Fe,
increased
FerriHn,
decreased
TIBC,
increased
Transferrin
saturaHon
• Decreased
iron
u3liza3on
causes
increased
iron
in
the
blood
and
increased
iron
storage
with
ferri3n.
TIBC
is
decreased
because
transferrin
levels
are
decreased
due
to
increased
iron
bound
to
the
transferrin.
This
will
increase
the
transferrin
satura3on.
BONUS
SLIDE
2
J
• Pure
Red
Cell
Aplasia
– NormocyHc
normochromic
– Primary
bone
marrow
disorder
where
only
erythroid
precursors
are
suppressed
– Parvovirus
B19,
Thymoma
– Decreased
or
absent
RBC
precursors,
Decreased
reHculocytes
Microcy3c
Anemia
Summary
Microcytic Anemias
Serum Fe Ferritin TIBC %sat RDW
Fe def
ACD NL NL NL
Thal NL NL NL NL NL
Siderob NL
• I
tones
it
down
this
3me
with
the
Canadian
flags
because
there
is
something
in
each
disease
that
is
very
testable.
So
to
make
up
for
it…
J
Ques3ons?
Comments?
Concerns?
Any
good
jokes?
Thanks
for
coming!!!!
J