Evaluation Flowchart | Table (MS Word) Anemias Table
by Megan Gold, CO 2012

Clinical SS
Lab test and reason why
Intravascular Hemolysis
Breakdown of hemoglobin in vessels.
↑free Hgb
↑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

Extravascular Hemolysis

Ingestion and clearance by macrophages in the Reticulo-endothelial system. Fe stored in ferritin and hemeàbili
Enterohepatic recirculation of urobilirubin after cleavage of glucuronic acid in gutà elevated levels of direct bili.
↑Direct bili (enterohepatic recirculation)

Glucose-6-Phosphate Dehydrogenase
-Intermittent acute hemolytic anemia
Protects against oxidative stressà ↓ G6PDà↓reduced glutathioneàlacks ability to help with oxidative stressà Hgb sticks to spectrin on RBC wallà abnml shapeàlysis by spleen
-sex-linked rec
Protein in urine (?)
Perif Smear (sometimes see)à
Blister cellsà cytoskeleton defect
Bite cellsà same
Usually NO morphology Δ
-Avoid oxidative foods (fava beans)
-supportive care
Hereditary Spherocytosis
-Anemia mild-mod
-Hyperbili in 1/3rd of neonates
-Aplastic crisis
-Bilirubin high à stoneàcholecystectomy
band 3 mutationsàweak cytoskeleton, spherical shapeàsplenic entrapment and easy to lyse
↑RetCàaccount for hemolysis
↑indir biliàtoo much heme to process
↓MCVàmaking too fast so microcytic
Osmotic fragility testàabnml/low
Spherocytes on smear
PK-Pyruvate Kinase Deficiency

Variable chronic anemia
Extravascular hemolysis
Aplastic crisis
Problemàpyruvate problemà ↓ATP productionà ↑2,3-BPG and mis-shapen RBCsàsplenic destruction
↑RetCàaccount for hemolysis
NO morphology Δ
-transfusions in severe cases
Autoimmune Hemolytic Disorders
Dark Urine
Acute/Chronic anemia
Splenectomy s.times


IgG and IgMàactivates C5-9 complementàRBC damage by complement
Bite cells
Direct Coombs (test for IgG, C3D, C4D-bound to RBC)à + Complement (C3D, C4D)
Indirect Coombs
(test for IgG and Complement-free in plasma)à
+ complement

Autoimmune Hemolytic Disorders
Dark Urine
Acute/Chronic anemia
Splenectomy s.times
IgG only
Macrophages and spleen affected so that the lysis is in the spleen and outside the blood system
Bite cells
Direct Coombs (test for IgG, C3D, C4D-bound to RBC)à + IgG (sometimes weak complement)
Indirect Coombs
(test for IgG and Complement-free in plasma)à
+ IgG

Iron Deficiency
Pain with exercise
Muscle problems
Neurological problems
Absorption problems
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
Perif Smear
Spherocytes, fragmented cells, target cells
Oral iron salts (150-200 mg tid)
IV/IM iron. 1st see serum Fe respond àRetC 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)
-Cyanosis without accompanying ↓ in arterial PP
-Brown-blood due to Fe+3 without change when exposed to O2
-In severe casesàbrady, respire depression, convulsions, acidosis.
-free radicals (NO, H2O2)
-Drugs (benzocaine)
-homozygous def of cytochrome-b-5-reductase (prevents reduction of Fe+3àFe+2)
-Hemoglobin M (mutation of chains that inhibits reduction of Fe+3)

Remove drug or chemical causing disease
Methylene Blue
Anemia of Chronic Disease/Inflammation
-Variable anemia
-Underlying inflammatory disease
-Renal insufficiency
-Thyroid disorder
-Adrenal insufficiency
-swelling (infections)
Inability to use iron stores and decrease EPO production result from inflammatory cytokines:
-TNF/IL-1à↓iron mobilization/ EPO production
-INFγ/βàinhibits erythropoisis
-Hepcidin (induced by cytokines) à↑ Fe storage, ↓duod abs, block Fe release from macrophages
-Hgb 8-12
-Usually Normocytic/ normochromic à 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)
↓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)
-Treat underlying condition to à ↓cytokines and
-Give iron
-Give EPO (especially with renal disease)
-Hormone replacement of endocrine disease
Lead Based Anemia
-Personality changes
-wt loss
-abdominal pain and vomiting
-Pb inhibits synthesis of protoporphyrin ringà↓heme
↓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)
1. REMOVE source of lead
2. Chelation
Sideroblastic Anemia
Variable anemia
Impaired production of protoporphyrin ring or incorporation of Fe into hemeà accumulation of iron in mitochondriaà Ring sideroblasts
↓MCV =
Pappenheimer bodies (ppt iron in mitochondriaàring around nucleus)
B6-s.times works
Tx of other underlying cause (Cu deficiency, EtOHism, drugs)
B-12 Deficiency
Slow (months) onset
CNS changes-cognitive dysfunction and emotional changes
Numbness, tingling, loss of fine sensations
CNS changes may be permanent.
Required for synthesis of methionine from homocysteineàprecursors for DNA synthesisàeffect erythropoisis in BM.
So essentially it is a disease of ↓DNA synthesis
-Vegan Diet-rare cause
-IF deficient = Pernicious Anemiaà (mal-abs of B12)
-autoimmune destruction of parietal cells that secrete IF
-Loss of ilial receptors-surgery, IBD
TcII deficiency
↑MVC =
Macrocytic/Normochromic (because increase in size as waiting for DNA to be made-arrest in S phase
↓RetC-because no B12 to make cells
Hypersegmented neutrophils-classical sign of B12 or folate deficiency.
-Nuclear-Cytoplasmic Asynchrony
M:E ratioàE 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
B-12 injections
Oral replacement
↑dosesàabs via mass action
Watch for other immune diseases
-Rapid response to treatment and slowly resolving CNS indicates accurate dx.
Folate Deficiency
Quick Onset (weeks)
Required for synthesis of methionine from homocysteineàprecursors for DNA synthesisàeffect erythropoisis in BM.
So essentially it is a disease of ↓DNA synthesis
Insufficient dietary intake*1⁰
Mal-absàparasitic infection (disrupts enterohepatic recirc)
EtOH consumption excess
↑MVC =
Macrocytic/Normochromic (because
↓RetC-because no B12 to make cells
Hypersegmented neutrophils
-Nuclear-Cytoplasmic Asynchrony
M:E ratioàE predominance
↑Homocysteine levels
↓serum folate
↓methylmalonic acid
Folate 1mg/d PO/IV/IM
Rapid recovery of CBC.
Sickle Cell Anemia
Chronic Hemolytic Anemia
Aplastic crisis - ↓RetC
Pain crisis – Acute chest pain, multi-organ failure, priapism, bone infaction.
Sickling cells are actually “sticky” which leads to vessel damage, endothelial remodeling and vessel narrowing. This microvessel damage affects all organs (lungs, retina, kidneys, spleen, CNS)
↑RetC-to compensate for hemolysis (except during aplastic crisis)
↑WBC/platelets due to BM response
↑RDW-increase production and constantly changing shape of the sickled cell
↓MCV – Microcytosis (Sβ/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
Polychromasia-blue colored cells
Anisocytosis (RDW effect)
Howell Jolly bodies-occur in pt w/out functional spleen due to injury/occlusion from sickled cellsàsplenic sequestration.
1. BM transplant w/ HLA matched sibling is 90%
2. Hydroxyureaà ↑Hb F
3. Transfusions – decrease pain crises extend life.
Hb H (Barts)
Mod-severe anemia
Infant Barts bodies = γ-4
H-bodies in adult
--/-α àlimited binding to gamma chain during in-utero development and then β-agglutination during life.
↓MCV – bc low α chains and agglutination of β-chains whichàBarts
↓MCHC-because low levels of heme since less produced
Transfusions s.times
Mild Anemia
Mild splenomegaly
Extramedullary Hematopoiesisàfrontal bossing, hair on ends, enlarged mandible etc
Hb E is an unstable globin chainà ↓amount for heme production
↓MCV =
↓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)
No transfusions
Cooley’s β-thal Major
Severe anemia
Extramedullary Hematopoiesis
2/3rds have abnml endocrine problems (hypothyroid, gonad problems etc)
2 severely abnml β-globin chains
↑ Levels of Hb F (10-90%)
↓MCV =
↓MCHC-because low levels of heme since less produced
Target cells = Mexican hat = Excess of RBC plasma membrane
ALWAYS transfusions
Always chelation tx
Hydroxyurea=↑HbF (via increasing gamma chains that can bind with the excess α-chains.

Evaluation Flowchart


Table (MS Word)

by Megan Gold, CO 2012