ANEMIAS

MICROCYTIC
Decreased production of Hb cell divides extra time to keep Hb concentration up
IRON DEFICIENCY

Decreased levels Hb
total iron heme Hb
microcytic anemia
Microcytic, hypochromic, RDW,
ferritin, TIBC, serum iron,
% sat
-bicycle tires!
Infants- breast feeding, Children- diet
Adults- peptic ulcer (males),
menorrhagia (females), Elderly- colon
polyps/carcinoma; esophageal web
-atrophic fissured tongue, spooning
ANEMIA CHRONIC DISEASE Assoc. w/ chronic inflamm or cancer; in
hosp. pts
available iron heme Hb
microcytic anemia
ferritin, TIBC, serum iron,
% sat
Results in production acute phase
reactants from liver, incl. hepcidin
(sequesters iron in storage sites to
prevent bacteria from getting it)
SIDEROBLASTIC ANEMIA

Defective protoporphyrin synthesis
protoporphyrin heme Hb
microcytic anemia
ferritin, TIBC, serum iron,
sat (from iron-overloaded state; iron
laden mitochondria form ring around
nucleus of erythroid precursors (ringer
sideroblasts)
-Congenital defects (ALAs)
-Acquired causes (alcoholism, lead
poisoning b/c inhibits ALAD and
ferrochelatase)
-Lead poisoning: basophilic stippling
THALASSEMIA

Decreased synthesis of globin chains
of Hg
globin Hb microcytic anemia
Microcytic, hypochromic RBCs with
target cells (incr membrane or decr
cytoplasm);
Massive erythroid hyperplasia (crew
cut X-ray, chipmunk facies)
thal = gene deletion
thal = gene mutations (point
mutations in promoter or splicing site)
MACROCYTIC
Upset in production of DNA precursors cell cant divide right amount of times
FOLATE DEFICIENCY

Deficiency in folate from diet,
increased demand, or antagonists
(methotrexate inhibits dihydrofolate
reductase)
Macrocytic RBCs and hypersegmented
neutorphils ( > 5 lobes);
homocysteine and normal
methylmalonic acid; glossitis
Develops within months because
stores limited
-treat with folate
VIT B12 DEFICIENCY

Deficiency B12 due to pernicious
anemia (autoimm destruction of
parietal cells IF deficiency),
pancreatic insuff, rarely diet
Macrocytic RBCs with
hypersegmented neutrophils;
homocysteine and methymalonic
acid; glossitis; subacute combined
degeneration of spinal cored
-Less common and takes years to
develop (large hepatic stores)
-Shilling test to test for IF
-Neuro symptoms not helped with
folatetherefore need to give B12
NORMOCYTIC WITH EXTRAVASCULAR HEMOLYSIS
Increased peripheral destruction
HEREDITARY SPHEROCYTOSIS

Inherited defect of RBC cytoskeleton-
membrane tethering proteins (spectrin,
ankrin, band 3.1) abnormal
blebbing; gets caught in spleen and
then eaten by macrophages anemia
Spherocytes with loss of central palor;
RDW, MCHC; splenomegaly,
jaundice with unconjugated bilirubin &
increase risk bilirubin gallstones;
Howell-Jolly bodies (small dark nuclear
remnants) in asplenic patients
-Diagnosis by osmotic fragility test
(spherocytes dont have enough room
to expand for increase in water)
-Stable course punctuated by aplastic
crisis (parvovirus B19)
SICKLE CELL ANEMIA

Auto recessive mutation in chain of
Hb; single amino acid change replaces
normal glutamic acid (hydrophilic) with
valine (hydrophobic); HbS polymerizes
when deoxygenated; continuous sickle
and de-sickle membrane damage;
(eventual intravasc. hemolysis as well)
Sickle cells
Target cells
Howell-Jolly bodies (due to
autosplenectomy)
Gamma-gandy bodies (in spleen)
-Massive erythroid hyperplasia
-Risk of aplastic crisis (parvovirus B19)
Screen with metabisulfite and
electrophoresis; increased risk for
incfection w/ encapsulated organisms
(pneumonia) must vaccinate;
increased risk of salmonella
osteomyelitis; acute chest syndrome
most common COD; fever in kids bad
HEMOGLOBIN C

Auto recessive mutation of chain of
Hb, glutamic acid replaced by lysine
-HbC crystals seen in RBCs
-Target cells
Mild anemia
NORMOCYTIC WITH INTRAVASCULAR HEMOLYSIS
Increased destruction
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA (PNH)
Acquired defect in myeloid stem cells
resulting in absent GPI; cells
susceptible to destruction by
complement (absence GPI = absence
DAF)
RBCs, WBCs and platelets lysed;
hemoglobinemia, hemoglobinuria (esp.
in morning), hemosiderinuria (days
after hemolysis)
Sucrose test activates complement
-main cause death thrombosis of
hepatic, portal or cerebral veins;
complications include iron def anemia
and AML
GLUCOSE-6_PHOSPHATE
DEHYDROGENASE (G6PD)
DEFICIENCY

X-linked recessive disorders
reduced half-life of G6PD so cells
susceptible to oxidative stress
G6PD NADPH
glutathione oxidative injury by H2O2
intravasc. hemolysis
Heinz bodies (precipitates of denatured
Hb - need special stain) & bite cells
(splenic phagocytes pluck out Heinz
bodies); hemoglobinuria and back pain
Two variants
-African: mildly reduced half-life mild
hemolysis w/ oxidative stress
-Mediterranean: markedly reduced
half-life marked intravascular
hemolysis w/ ox stress
Ox stress caused by fava beans or
drugs (primaquine)
IMMUNE HEMOLYTIC ANEMIA (IHA)

1. Warm: IgG-mediated, extravascular
hemolysis, spherocytes, SLE
2. Cold: IgM-mediated, intravascular
hemolysis, Reynauds, cold agglutinin,
pneumaniae
Polychromasia; spheroctyes; small
fragmented red cell (triangle);
polychromatophilic red cells (big,
bluish); few red cells on smear
Coombs Test (DAT)
-Direct: confirms presence Ab-coated
RBCs
-Indirect: presence of Abs in patients
serum
MICROANGIOPATHIC HEMOLYTIC
ANEMIA

Mechanical trauma intravascular
hemolysis results from vascular
pathology; RBCs destroyed as they
pass thru circulation cheese cutter
Schistocytes (helmet cells) -Occurs with microthrombi (TTP-HUS,
DIC, HELLP), prosthetic heart valves,
and aortic stenosis
-Iron deficiency anemia can occur
MALARIA Infection of RBCs and liver with
Plasmodium transmitted by female
Anopheles mosquito; RBCs rupture as
part of the Plasmodium life cycle
intravasc hemolysis and cyclical fever
Splenomegaly, banana shape P falciparium- daily fever
P vivax and ovale- fever every other
day
ANEMIA DUE TO UNDERPRODUCTION
Decreased production of RBCs by bone marrow w/ low corrected reticulocyte count
PARVOVIRUS B19

Infects progenitor red cells and
temporarily halts erythropoiesis
significant anemia in setting of
preexisting marrow stress
Treatment supportive; is self-limiting
APLASTIC ANEMIA

Damage to hematopoietic stem cells
pancytopenia w/ low reticulocyte count
-from drugs, chemicals, viral infection,
and autoimmune damage
Empty fatty marrow (biopsy)causes=
Fanconi anemia defect in DNA repair
Diamond-Blackfan anemia congenital
erythroid aplasia
Telomerase defect
Treatment includes cessation
causative drugs, supportive care w/
transfusions and marrow-stimulating
factors; immunosuppression can be
helpful
MYELOPHTHISIC PROCESS Pathologic process (eg metastatic
cancer) that replaces bone marrow
Teardrop shaped RBCs
Epithelial cells
Hematopoeisis is impared
pancytopenia