Cause Pathogenesis Clinical Laboratory findings Treatment

Presentation
Microcytic anemias
MCV <80
Anemia develops due to decreased production of hemoglobin ( heme + globin or iron + protoporphyrin + globin)
Microcytosis develops due to extra division to maintain hemoglobin concentration
Iron deficiency Decreased levels of iron by Deficiency depletion of Most common type TIBC, FEP Supplemental
anemia diet or hemorrhage storage iron depletion of of anemia Ferritin, Serum Iron Ferrous
impaired heme synthesis serum iron normocytic Iron, % Saturation sulfate
anemia microcytic Anemia
Infants - breastfeeding hypochromic (weakness, PBS: microcytic,
Children poor diet fatigue, hypochromic RBCs,
Adults peptic ulcer disease Deficiency can result from dyspnea, pale anisopoikilocytosis,
(M); menorrhagia/pregnancy deficiency (nutritional or conjunctiva and thrombocytosis
(F) absorptional problem) or skin, headache,
increased loss (bleeding lightheadedness
either menstrual or , angina
typically GI bleeding) especially with
pre-existing
CAD)
Koilonychia
Pica
Plumber-Vinson
Syndrome
(esophageal web,
dysphagia,
atrophic glossitis =
beefy red tongue)
Anemia of Decreased levels of iron due Chronic inflammation or Most common Ferritin, FEP Address
chronic disease to Increased sequestration cancer increased anemia in TIBC, Serum Iron, underlying
of iron in storage sites production of acute phase hospitalized % Saturation cause
reactants, in particular patients
Hepcidin Exogenous EPO
Anemia useful in subset
Hepcidin sequesters iron in of patients, esp
storage sires by limiting those w/t
iron transfer from cancer
macrophages to erythroid
precursors AND
suppressing EPO
Sideroblastic Defective protoporphyrin Protoporphyrin synthesized Anemia ferritin, Serum
anemia synthesis can be via series of reactions Iron, % Saturation
congenital and acquired TIBC
 - Succinyl-coA ALA via (iron-overloaded
Congenital: ALAS defect ALAS (vit b6 cofactor) state)
- ALA porphobilinogen
Acquired: via ALAD PBS: Ringed
Alcoholism mito poison - Porphobilinogen sideroblasts
Lead poisoning: inhibits Protoporphyrin
ALAD and ferrochelatase - Protoporphyrin + iron
Vitamin B6 deficiency heme via ferrochelatase
inhibits ALAS (isoniazid)
Thalassemia Inherited mutation resulting due to gene deletion; 1 deletion: HbH and Hb barts
in decreased synthesis of 4 alpha alleles on asymptomatic can be seen on
globin chains chromosome 16 2 deletions: mild electrophoresis
anemia, increased
RBC count
3 deletions: severe
anemia, chains
form tetramers
that damage RBC
membrane (HbH)
4 deletions: lethal
in utero (hydrops
fetalis); chains
form tetramers (Hb
Barts) that
damage RBCs

due to gene thalassemia PBS: Chronic

mutation; 2 beta alleles minor: usually minor: microcytic, transfusions
on chr. 11 asymptomatic with hypochromic RBCs increased risk
increased RBC + target cells of
thalassemia major: count major: hemochromato
- unpaired chains microcytic, sis
precipitate and damage thalassemia hypochromic RBCs
RBC membrane major: + target cells +
ineffective erythropoiesis - severe anemia a nucleated RBCs
and extravascular few months after
hemolysis birth due to in X-ray: thalassemia
- massive erythroid HbF major: crew-cut
hyperplasia expansion - chipmunk facies appearance
of hematopoiesis into the -
skull and facial bones hepatosplenomega Electrophoresis
+ extramedullary ly Minor: increased
hematopoiesis HbA2
hepatosplenomegaly Major: lack of HbA
- at risk for aplastic crisis
with parvovirus b19
infection
Macrocytic anemias
MCV >100
Megaloblastic anemia = due to folate or vitamin B12 deficiency
Other causes: alcoholism, liver disease, drugs (5-FU) no megaloblastic change with these causes
Folate deficiency Impaired synthesis of DNA Absorbed in jejunum from Glossitis PBS:Macrocytic
precursors green vegetables and (inflammation of RBCs
some fruits tongue b/c tongue Hypersegmented
Impaired division of RBC and Deficiency develops within rapidly turns over) neutrophils,
granulocytic precursors months pancytopenia
megaloblastic anemia and
hypersegmented neutrophils Causes: Normal
Poor diet alcholics, methylmalonic acid
Megaloblastic change also elderly Serum
seen in rapidly-dividing increased demand preg, homocysteine
epithelial cells cancer, hemolytic, anemia Serum folate
folate antagonists
methotrexate

Vitamin B12 Absorbed in terminal Glossitis PBS: Macrocytic

deficiency ileum via intrinsic factor Subacute RBCs
from animal proteins combined Hypersegmented
Deficiency develops over degeneration of neutrophils,
years (large hepatic stores) spinal cord pancytopenia

Causes: serum
- Autoimmune destruction homocysteine,
of parietal cells leads to Methylmalonic acid
intrinsic factor deficiency Serum Vitamin
(pernicious anemia) B12
- Pancreatic insufficiency
leads to decreased R-
binder
- Damage to terminal ileum
(Crohns disease,
tapeworm)
- Diet i.e Vegan
Normocytic anemia
MCV = 80-100; normal size
Due to increased peripheral destruction (hemolysis) or underproduction

Reticulocyte count helps to distinguish between the 2 etiologies

Corrected RC >3% indicates good marrow response and suggests peripheral destruction
Corrected RC <3% indicates poor marrow response and suggests underproduction

Peripheral RBC destruction can be divided into extravascular and intravascular hemolysis both result in anemia with good marrow
response
Extravascular hemolysis is RBC destruction by reticuloendothelial system (macrophages of spleen, liver, and lymph nodes) anemia
with splenomegaly, jaundice due to unconjugated bilirubin, increased risk for bilirubin gallstones, marrow hyperplasia
Intravascular hemolysis is RBC destruction within vessels Hemoglobinuria, Hemoglobinemia, Hemosiderinuria, decreased serum
Haptoglobin (4Hs)
Both have increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors

Hereditary Inherited defect of RBC -Cell become round - Jaundice with Osmotic fragility Splenectomy
spherocytosis cytoskeleton membrane (spherocytes) over time unconjugated test spherocytes Anemia
proteins (ankyrin, spectrin, due to membrane bilirubin are more fragile in resolves but
or Band 3) blebbing/lost -Splenomegaly hypotonic solution spherocytes
-Increased risk for due to membrane persist plus
-Spherocytes are less able gallstones weakness Howell-Jolly
to maneuver splenic -Increased risk for bodies
sinusoids and are aplastic crisis with
consumed by splenic parvovirus B-19
macrophages infection
Extravascular hemolysis
Sickle cell Autosomal recessive HbS polymerizes when Usually presents at PBS: sickle cells + Hydroxyurea
anemia mutation in beta chain, Glu deoxygenated (hypoxia, 6 mos of age when target cells in SCD
6 Val 6 substitution dehydration, acidosis) HbF decreases
aggregates sickle cells Metabisulfite screen
Homozygous = sickle cell EH anemia, (HbS sickling)
disease (SCD): >90% HbS in Sickle/de-sickle in jaundice, bilirubin positive in both SCD
RBCs microcirculation RBC gallstones and SCT
membrane damage IH target cells on
Heterozygote = sickle cell - Extravascular hemolysis blood smear, Hb Electrophoresis
trait (SCT): <50% HbS, - Intravascular hemolysis decreased presence and
asymptomatic no sickling - Massive erythroid haptoglobin amount
except in renal medulla hyperplasia expansion MEH crewcut (confirmatory)
which will eventually cause of hematopoiesis into skull appearance on
decreased ability to and face + extramedullary Xray and
concentrate urine hematopoiesis chipmunk facies
 (provides resistance to
Falciparum malaria) Risk for developing
aplastic crisis with
parvovirus B19
infection

Extensive sickling
leads to vaso-
occlusion
-Dactylitis
-autosplenectomy
-acute chest
syndrome
-pain crises
-renal papillary
necrosis
Hemoglobin C Autosomal recessive Mild anemia due to PBS: HbC crystals
mutation in beta chain Glu extravascular (rhomboid shape)
6 Lys 6 hemolysis

Paroxysmal Acquired defect in myeloid DAF (Decay accelerating Hemoglobinemia Screening: Sucrose
nocturnal stem cell resulting in absent factor) is present on and test
hemoglobinuria GPI surface of blood cells via hemoglobinuria
(PNH) Mutation in PIG-A gene GPI protects RBCs from especially in the Confirmatory test:
complement-mediated morning Acidified Serum Test
damage by inhibiting C3 or Flow Cytometry
convertase Hemosiderinuria is to detect lack of
Mutation absent GPI seen days after CD55 (DAF) on
no DAF on blood cells hemolysis blood cells
complement-mediated
intravascular hemolysis Main cause of
(RBCs, WBCs, platelets all death =
affected) thrombosis
(release of platelet
Hemolysis occurs at night cytoplasmic
during sleep b/c shallow contents into
breathing mild circulation)
respiratory acidosis
activation of complement Complications:
- Iron deficiency
anemia
- AML (~10% of
patients)
 - Aplastic anemia
G6PD Deficiency X linked recessive genetic Oxidative stress: Hemoglobinuria, Heinz preparation
disorder that results in infections, fava beans, back pain hours
reduced half life of G6PD drugs (primaquine, sulfa after exposure to Enzymatic studies:
increased susceptibility to drugs, dapsone) oxidative stress Must do after acute
oxidative stress acute intermittent episode resolves
amount of G6PD anemia
African variant mildly NADPH Reduced
reduced Glutathione Oxidative
Mediterranean variant injury by H2O2
markedly reduced Intravascular hemolysis

Carriers are protected Oxidative stress

against Falciparum malaria precipitates Hb Heinz
bodies
Heinz bodies removed from
RBCs by splenic
macrophages Bite cells

Immune Antibody-mediated IgG-mediated or warm Anemia Coombs test Cessation of

Hemolytic destruction of RBCs antibody -Direct: offending drug
anemia immunohemolytic Anti- -Steroids
anemia IgG/complement -IVIG
-IgG binds RBCs in warm added to patients -Splenectomy
temp/central body RBCs
-Membrane of Ab-coated agglutination
RBCs consumed by splenic indicates presence
macrophages of Ab/Complement
spherocytes coated RBCs
Causes: SLE, CLL, Drugs -Indirect: Anti-IgG
(penicillin/Ab-drug-mem and test RBCs mixed
complex), - w/ pts serum
methydopa/autoAb) detects presence of
antibodies in serum
IgM-mediated or cold
agglutination
immunohemolyic
anemia
- IgM binds RBCs and fixes
complement in extremities
(cold temp)
intravascular hemolysis
- RBCs may be able to
 inactivate complement but
residual C3b signals
opsonization by splenic
macrophages
extravascular hemolysis
Associated with B-cell
neoplasms and infections
(M. pneumonia and
Infectious mononucleosis
(EBV, CMV))
Microangiopathic RBCs destroyed by RBCs are injured as they Anemia PBS: Schistocytes
hemolytic microthrombi pass through the
anemia circulation by:
-Microthrombi (TTP-HUS,
DIC, HELLP)
-Prosthetic valves
-Aortic stenosis
Schistocytes
Malaria Infection of RBCs with RBCs rupture as part of Infectious Erythrocytes Anti-malarials
Plasmodium lifecycle intravascular hemolytic anemia infected with
hemolysis Cyclical fever Plasmodium

Spleen consumes some Possible

infected RBCs mild splenomegaly
extravascular hemolysis
Aplastic anemia Damage to hematopoietic Drugs or chemicals Anemia, Bone marrow Cessation of
stem cells pancytopenia Viral infections reticulocytopenia, biopsy: empty, fatty any causative
with low reticulocyte count Autoimmune damage neutropenia, marrow drugs
thrombocytopenia
Supportive care
Marrow
Other: Pancytopenia Pathologic process such as
Myelophthisic metastatic cancer replaces
process bone marrow and impairs
hematopoiesis
Other: Infection Infection of progenitor
Parvovirus B19 RBCs which temporarily
halts erythropoiesis
causes significant anemia
in setting of pre-existing
marrow stress (e.g sickle
cell anemia)