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Anemia
Classification:
according to underlying mechanism
1.
2.
3.
Blood loss
Increased Red cell destruction
Decrease Red cell production
Clinical findings
common complaints
Patients appear pale. Weakness, malaise, and easy
fatigability are
Intravascular
shift
hemodilution
reduction in
oxygenation
increased secretion of
erythropoietin from the
kidney
proliferation
proliferation of
committed
erythroid
progenitors (CFUE) in the marrow
Hemolytic Anemias
Features:
A shortened red cell life span below 120 days
Elevated erythropoietin levels and a compensatory
increase in erythropoiesis
Accumulation of hemoglobin degradation products that
recreated as part of the process of red cell hemolysis
Hemolytic anemia
extravascular hemolysis,- premature destruction of red cells also
occurs within phagocytes,
free hemoglobin
released from lysed
red cells
heme groups
-catabolized to bilirubin
within mononuclear
phagocytes
bound by haptoglobin
free hemoglobin
oxidizes to
methemoglobin,
reabsorb and
catabolize hemoglobin
and methemoglobin
Jaundice.
MORPHOLOGY
increased numbers of erythroid precursors (normoblasts) in
the marrow
Compensatory increases in erythropoiesis result in a prominent
reticulocytosis in the peripheral blood.
The phagocytosis of red cells leads to the accumulation of the
iron containing pigment hemosiderin
If the anemia is severe, extramedullary hematopoiesis can
appear in the liver, spleen, and lymph nodes.
Hereditary Spherocytosis
Hereditary spherocytosis (HS) is an inherited disorder
caused by intrinsic defects in the red cell membrane
skeleton that render red cells spheroid, less
deformable, and vulnerable to splenic sequestration
and destruction
pathogenesis
HS is caused by diverse mutations that lead to an insuf ciency of
membrane skeletal components.
life span of RBC- 10 to 20 days
The pathogenic mutations most commonly affect
ankyrin,
band 3,
spectrin, or
band 4.2,
mutations cause
frameshifts or
introduce
premature stop
codons,
Deficiency of the
affected protein
reduces the
assembly of the
skeleton as a whole
Young HS red cells are normal in shape, but the destabilized lipid bilayer sheds membrane fragments
destabilizing the
overlying plasma
membrane.
Morphology
The most specific morphologic finding is
spherocytosis, apparent on smears as small, darkstaining (hyperchromic) red cells lacking the central
zone of pallor
Spherocytosis is distinctive but not pathognomonic
Cholelithiasis (pigment stones) occurs in 40% to 50%
of affected adult
Moderate splenomegaly is char chracteristic (5001000 gm)
Clinical feature
The diagnosis is based on family history, hematologic ndings, and
laboratory evidence.
2/3 of the patients the red cells are abnormally sensitive to
osmotic lysis
HS red cells also have an increased mean cell hemoglobin
concentration,
anemia,
splenomegaly
jaundice.
HS presents at birth with marked jaundice and requires exchange
transfusions
In 20% to 30% of patients the disease is so mild as to be virtually
asymptomatic
The generally stable clinical course is sometimes punctuated by
aplastic crises, >> acute parvovirus infection
Hemolytic crises are produced by intercurrent events leading to
Glucose-6-Phosphate Dehydrogenase
Deciency
Abnormalities in the hexose monophosphate shunt or
glutathione metabolism
hereditary deficiency of glucose-6-phosphate dehydrogenase
(G6PD) activity
Reduce ability of RBC to protect themselves against
oxidative injuries and lead to hemolysis
Drugs
Antimalarials (e.g., primaquine and
chloroquine),
sulfonamides,
nitrofurantoins,
Oxidant
cross linking of
reactive
sulfhydryl groups
on globin chain
become
denatured and
precipitate
As inclusion-bearing
red cells pass through
the splenic cords,
macrophages pluck out
the Heinz bodies.
formation of
Heinz bodies
Pathogenesis
The major pathologic manifestations
chronic hemolysis,
microvascular occlusions, and
tissue damage
reduces the oxygen af nity of hemoglobin, thereby increasing the fraction of deoxygenated
HbS at any given oxygen tension and augmenting the tendency for sickling
Morphology
In sickle cell anemia, the peripheral blood demonstrates variable
numbers of irreversibly sickled cells, reticulocytosis, and
target cells, which result from red cell dehydration
Howell-Jolly bodies (small nuclear remnants) are also present in
some red cells due to the asplenia
The bone marrow is hyperplastic as a result of a compensatory
erythroid hyperplasia.
Morphology
expansion of the marrow leads to bone resorption and
secondary new bone formation, resulting in
prominent cheekbones and changes in the skull that
resemble a crewcut on x-ray studies
Extramedullary hematopoiesis can also appear. The
increased breakdown of hemoglobin can cause
pigment gallstones and hyperbilirubinemia.
Morphology
In early childhood, the spleen is enlarged up to 500 gm by
red pulp congestion
Clinical Features
Sickle cell disease causes a moderately severe
hemolytic anemia (hematocrit 18% to 30%)
Associated with reticulocytosis,
hyperbilirubinemia, and the presence of
irreversibly sickled cells.
Its course is punctuated by a variety of crises.
Vasoocclusive crises, also called pain crises
The most common sites -bones, lungs, liver, brain,
spleen, and penis
Diagnosis
The diagnosis is suggested by the clinical findings and
the presence of irreversibly sickled red cells
confirmed by various tests for sickle hemoglobin
involve mixing a blood sample with an oxygen- consuming
reagent, such as metabisulfate, which induces sickling of red
cells if HbS is present
Hemoglobin electro- phoresis is also used to demonstrate the
presence of HbS and exclude other sickle syndromes, such as
HbSC disease.
Prenatal diagnosis is possible by analysis of fetal DNA obtained
by amniocentesis or chorionic biopsy.
Prognosis
The outlook for patients with sickle cell disease
has improved considerably over the past 10 to 20
years.
About 90% of patients survive to age 20, and close to
50% survive beyond the fth decade