Disease
Intravascular
Hemolysis
Clinical SS
Splenomegaly
Extravascular
Hemolysis
Glucose-6-Phosphate
Dehydrogenase
-Intermittent acute
hemolytic anemia
-hyperbilirubinemia
Hereditary
Spherocytosis
-Anemia mild-mod
-Jaundice
-Splenomegaly
-Hyperbili in 1/3rd of
neonates
-Aplastic crisis
-Bilirubin high 
stonecholecystectomy
Pathophysiology/Cause
Breakdown of hemoglobin in
vessels.
Lab test and reason why
↑free Hgb
↑LDH
↑SGOT
↑RetC-to compensate for hemolysis
↑RDW-fast output old and new cells
Hemoglobinuria/plasma – b/c cannot process all.
↑ Indir bili-overloaded system cannot keep up with
demand so bili does not get conjugated to
glucuronic acid
↑Metheme/methemoglobin-b/c broken free heme
byproduct
↓Haptoglobin-taken out of serum when binds
heme to the liver
Ingestion and clearance by
macrophages in the Reticuloendothelial system. Fe stored
in ferritin and hemebili
Enterohepatic recirculation of
urobilirubin after cleavage of
glucuronic acid in gut
elevated levels of direct bili.
Protects against oxidative
stress ↓ G6PD↓reduced
glutathionelacks ability to
help with oxidative stress
Hgb sticks to spectrin on RBC
wall abnml shapelysis by
spleen
-sex-linked rec
Spectrin/ankyrin/
band 3 mutationsweak
cytoskeleton, spherical
shapesplenic entrapment
and easy to lyse
↑LDH
↑SGOT
↑RetC
↑RDW
↑Direct bili (enterohepatic recirculation)
Treatment
Protein in urine (?)
Perif Smear (sometimes see)
Microspherocytes
Blister cells cytoskeleton defect
Bite cells same
Usually NO morphology Δ
-Folate
-Avoid oxidative
foods (fava beans)
-supportive care
Hct-variable
Hgb-variable
↑RetCaccount for hemolysis
↑indir bilitoo much heme to process
↓MCVmaking too fast so microcytic
Osmotic fragility testabnml/low
Spherocytes on smear
splenectomy
PK-Pyruvate Kinase
Deficiency
Autoimmune
Hemolytic Disorders
COLD/INTRAvascular
Variable chronic anemia
Extravascular hemolysis
Splenomegaly
Gallstones
Aplastic crisis
Dark Urine
Acute/Chronic anemia
Pallor/Jaundice
Splenectomy s.times
Problempyruvate
problem ↓ATP
production ↑2,3-BPG and
mis-shapen RBCssplenic
destruction
IgG and IgMactivates C5-9
complementRBC damage by
complement
↑RetCaccount for hemolysis
NO morphology Δ
SAME FOR EXTRA
↓
-Folate
-Spenectomy-s.times
-transfusions in
severe cases
↑RetC
↑Bili
Hemoglobinuria
Spherocytes
Bite cells
Direct Coombs (test for IgG, C3D, C4D-bound to
RBC) + Complement (C3D, C4D)
Indirect Coombs
(test for IgG and Complement-free in plasma)
+ complement
Autoimmune
Hemolytic Disorders
WARM/EXTRAvasc.
Dark Urine
Acute/Chronic anemia
Pallor/Jaundice
Splenectomy s.times
IgG only
Opsonizing
Macrophages and spleen
affected so that the lysis is in
the spleen and outside the
blood system
↑RetC
↑Bili
Hemoglobinuria
Spherocytes
Bite cells
Direct Coombs (test for IgG, C3D, C4D-bound to
RBC) + IgG (sometimes weak complement)
Indirect Coombs
(test for IgG and Complement-free in plasma)
+ IgG
Iron Deficiency
Fatigue
Pallor
Pain with exercise
SOB
Tachycardia
Muscle problems
Neurological problems
Dietary
Absorption problems
Inflammation/Infection
Cytokine production
Microcytic and Hypochromic
↓Hgb-no iron to bind heme
↓Hct-less and smaller RBC’s bc no iron
↓ferritin-iron stores used up
↓RetC-because no iron to make RBC’s
↓serum iron
↑TIBC-bc capacity is increased due to no binding
↑RDW
Perif Smear
Spherocytes, fragmented cells, target cells
Oral iron salts (150200 mg tid)
IV/IM iron. 1st see
serum Fe respond
RetC nmlizes, Hgb
nml after 7- 10 days.
Continue treatment
until ferritin stores
returned and MCV
and RDW are nml
(which will take 100
days or so until
abnml RBC’s have
been removed)
Methemoglobinemia
-Cyanosis without
accompanying ↓ in
arterial PP
-Brown-blood due to
Fe+3 without change
when exposed to O2
-In severe casesbrady,
respire depression,
convulsions, acidosis.
Acquired
-free radicals (NO, H2O2)
-Drugs (benzocaine)
Hereditary
-homozygous def of
cytochrome-b-5-reductase
(prevents reduction of
Fe+3Fe+2)
-Hemoglobin M (mutation of
chains that inhibits reduction
of Fe+3)
Anemia of Chronic
Disease/Inflammatio
n
-Variable anemia
-Underlying inflammatory
disease
-Renal insufficiency
-Thyroid disorder
-Adrenal insufficiency
-fever
-arthritis
-swelling (infections)
Inability to use iron stores and
decrease EPO production
result from inflammatory
cytokines:
-TNF/IL-1↓iron
mobilization/ EPO production
-INFγ/βinhibits
erythropoisis
-Hepcidin (induced by
cytokines) ↑ Fe storage,
↓duod abs, block Fe release
from macrophages
Lead Based Anemia
-Personality changes
-irritability
-weakness
-wt loss
-abdominal pain and
vomiting
-Pb inhibits synthesis of
protoporphyrin ring↓heme
Sideroblastic Anemia
Variable anemia
Impaired production of
Acquired
Remove drug or
chemical causing
disease
Hereditary
Methylene Blue
-Hgb 8-12
-Usually Normocytic/ normochromic  microcytic
/mild hypochroma
↓RetC –reticulocytopenia b/c cannot get iron since
sequestered due to presence of hepcidin.
↑Ferritin-due to increased/sequestration of
iron(DIFF from Iron defic anemia)
↓TIBC (DIFF from IDA)
↓Serum Iron (like IDA)
↓Transferrin saturation (as with IDA)
↓EPO for degree of anemia (espec with renal
disease. But usually not seen until <40% renal
function)
↓MCV =
Microcytic/hypochromic because Pb is preventing
production of porphyrin ring
↓RetC-because no heme to make iron so cannot
make RBC’s
↑Lead levels
Basophilic stippling-aggregates of RNA(also seen
with macrocytic anemia of B12 and Folate)
-Treat underlying
condition to 
↓cytokines and
inflammation
-Give iron
-Give EPO (especially
with renal disease)
-Hormone
replacement of
endocrine disease
↓MCV =
B6-s.times works
1. REMOVE source of
lead
2. Chelation
protoporphyrin ring or
incorporation of Fe into
heme accumulation of iron
in mitochondria Ring
sideroblasts
Required for synthesis of
methionine from
homocysteineprecursors for
DNA synthesiseffect
erythropoisis in BM.
So essentially it is a disease of
↓DNA synthesis
Causes
-Vegan Diet-rare cause
-IF deficient = Pernicious
Anemia (mal-abs of B12)
-autoimmune destruction of
parietal cells that secrete IF
-Loss of ilial receptors-surgery,
IBD
TcII deficiency
Microcytic/hypochromic
Pappenheimer bodies (ppt iron in
mitochondriaring around nucleus)
↑MVC =
Macrocytic/Normochromic (because increase in
size as waiting for DNA to be made-arrest in S
phase
↓RBC
↓RetC-because no B12 to make cells
Hypersegmented neutrophils-classical sign of B12
or folate deficiency.
↑RDWanisocytosis
-Nuclear-Cytoplasmic Asynchrony
M:E ratioE predominance
↑Homocysteine levels
↑methylmalonic acid
↑ to nml serum folate*
↓B-12 levels (s.times predictive)
Shillings Test: If abnml then add IF and see if
corrects. If normal then not B-12 abs problem
Transfusions
Tx of other
underlying cause (Cu
deficiency, EtOHism,
drugs)
B-12 injections
Oral replacement
↑dosesabs via
mass action
Watch for other
immune diseases
-Rapid response to
treatment and slowly
resolving CNS
indicates accurate dx.
B-12 Deficiency
Slow (months) onset
CNS changes-cognitive
dysfunction and
emotional changes
Numbness, tingling, loss
of fine sensations
Proprioception
Ataxia
CNS changes may be
permanent.
Folate Deficiency
Quick Onset (weeks)
Required for synthesis of
methionine from
homocysteineprecursors for
DNA synthesiseffect
erythropoisis in BM.
So essentially it is a disease of
↓DNA synthesis
Causes
Insufficient dietary intake*1⁰
Mal-absparasitic infection
(disrupts enterohepatic recirc)
EtOH consumption excess
↑MVC =
Macrocytic/Normochromic (because
↓RBC
↓RetC-because no B12 to make cells
Hypersegmented neutrophils
↑RDWanisocytosis
-Nuclear-Cytoplasmic Asynchrony
M:E ratioE predominance
↑Homocysteine levels
↓serum folate
↓methylmalonic acid
Folate 1mg/d
PO/IV/IM
Rapid recovery of
CBC.
Sickle Cell Anemia
Chronic Hemolytic
Anemia
Sickling cells are actually
“sticky” which leads to vessel
↑RetC-to compensate for hemolysis (except during
aplastic crisis)
1. BM transplant w/
HLA matched sibling
Aplastic crisis - ↓RetC
Pain crisis – Acute chest
pain, multi-organ failure,
priapism, bone infaction.
damage, endothelial
remodeling and vessel
narrowing. This microvessel
damage affects all organs
(lungs, retina, kidneys, spleen,
CNS)
Hb H (Barts)
Mod-severe anemia
Infant Barts bodies = γ-4
H-bodies in adult
Hb EE
Mild Anemia
Mild splenomegaly
Extramedullary
Hematopoiesisfrontal
bossing, hair on ends,
enlarged mandible etc
Severe anemia
Extramedullary
Hematopoiesis
2/3rds have abnml
endocrine problems
(hypothyroid, gonad
problems etc)
--/-α limited binding to
gamma chain during in-utero
development and then βagglutination during life.
Hb E is an unstable globin
chain ↓amount for heme
production
Cooley’s β-thal Major
2 severely abnml β-globin
chains
↑ Levels of Hb F (10-90%)
↑WBC/platelets due to BM response
↑RDW-increase production and constantly
changing shape of the sickled cell
↓MCV – Microcytosis (Sβ⁰/Sβ+)
Heme C crystals = red rods in RBC’s (SC disease)
↑Hb Fetal (2-30%)
↑LDH, AST (released from lysed RBC)
↑indirect bilirubin-due to hemolysis
↑Total bilirubin
Perif Smear
Schistocytes
Polychromasia-blue colored cells
Anisocytosis (RDW effect)
Howell Jolly bodies-occur in pt w/out functional
spleen due to injury/occlusion from sickled
cellssplenic sequestration.
↓MCV – bc low α chains and agglutination of βchains whichBarts
↓MCHC-because low levels of heme since less
produced
↓MCV =
Microcytic
↓MCHC-because low levels of heme
Target cells = Mexican hat = Excess of RBC plasma
membrane due to ↓in heme content to RBC itself
(RBC is not filled up so takes on this shape)
↓MCV =
Microcytic
↓MCHC-because low levels of heme since less
produced
Target cells = Mexican hat = Excess of RBC plasma
membrane
is 90%
2. Hydroxyurea
↑Hb F
3. Transfusions –
decrease pain crises
extend life.
Transfusions s.times
No transfusions
ALWAYS transfusions
Always chelation tx
Hydroxyurea=↑HbF
(via increasing
gamma chains that
can bind with the
excess α-chains.