HEMATOPATHOLOGY

RED BLOOD CELL PATHOLOGY: ANEMIAS

RED BLOOD CELL MORPHOLOGY

• RED CELL SHAPES
• Abnormal size is called anisocytosis (aniso
means unequal)
• Abnormal shape is called poikilocytosis (poikilo
means various)
• Elliptocytes may be seen in hereditary
elliptocytosis.
• Spherocytes result from decreased erythrocyte
membrane and they may be seen in hereditary
spherocytosis and in autoimmune hemolytic
anemia
• Schistocytes are erythrocyte fragments
(helmet cells are a type of schistocyte); seen in
microangiopathic hemolytic anemias or
traumatic hemolysis
• Bite cells are erythrocytes with “bites” of cytoplasm
being removed by splenic macrophages; seen in G6PD
deficiency.
• Teardrop cells (dacrocytes) may be seen in
thalassemia and myelofibrosis
• Sickle cells (drepanocytes) are seen in sickle cell
anemia.
• Rouleaux (“stack of coins”) refers to erythrocytes
lining up in a row. are characteristic of multiple
myeloma
 ANEMIAS
• Anemia is a reduction below normal limits of
the total circulating red cell mass
• Signs of anemia include palpitations,
dizziness, angina, pallor of skin and nails,
weakness, claudication, fatigue, and lethargy
• Reticulocytes are immature, larger red cells
(macrocytic cells)
• are spherical and have a bluish color
(polychromasia) due to free ribosomal RNA
• Reticulocytes do not have a nucleus; note that
any erythrocyte with a nucleus (nRBC) in
peripheral blood is abnormal
• Reticulocyte maturation to a mature erythrocyte
takes about 1 day.
• The reticulocyte count is the percentage of red
immature cells present in peripheral blood
(normal 0.5– 1.5%).
• The corrected reticulocyte count takes into
consideration the degree of anemia and is
calculated as (patient’s hct/45) × (reticulocyte
count)
• The reticulocyte production index is the
corrected reticulocyte count/2
Red blood cell indices:
• Mean corpuscular volume (MCV): average volume of a
red blood cell
• Mean corpuscular hemoglobin (MCH): average content
(mass) of hemoglobin per cell
• Mean corpuscular hemoglobin concentration (MCHC):
average concentration of hemoglobin in a given volume
of packed erythrocytes
• Red cell distribution width (RDW): coefficient of variation
of red blood cell volume and a measure of anisocytosis
 Classification of anemia
• based on color
– normochromic anemias - normal red cell color
(central pallor of about a third the diameter of the
erythrocyte)
– hypochromic anemias - decreased color (increased
central pallor of erythrocyte)
– ‘’hyperchromic anemias’’ - instead called
spherocytosis and have increased color (loss of
central pallor of erythrocyte)
• based on size (MCV)
• The pathogenesis of anemia
– Blood loss
– Hemolysis
– diminished erythropoiesis
 MICROCYTIC ANEMIAS
Iron deficiency anemia
• Iron is available in the body in different
forms
– Functional iron - found in hemoglobin,
myoglobin, and enzymes (catalase and
cytochromes)
– Ferritin (physiological storage form ) - plasma
ferritin is normally close to the total body Fe
– hemosiderin (Prussian blue positive) - iron
precipitated in tissues in the form of degraded
ferritin mixed with lysosomal debris
– Iron is transported in the blood stream by
transferrin - Transferrin saturation is reported as
a percentage
 Causes of iron deficiency
• Dietary deficiency of iron
• Increased demand for iron
• decreased absorption
• chronic blood loss due to
gynecologic (menstrual bleeding)
or gastrointestinal causes
• Anemia of chronic disease (AOCD)
(or anemia of inflammation)
• Thalassemia syndromes
• Sideroblastic anemia
 NORMOCYTIC ANEMIAS
1. Anemias of blood loss –
• Acute blood loss - may cause shock or death.
• If the patient survives, the resulting
hemodilution caused by shift of water from
the interstitium will lower the hematocrit.
• There will be a marked reticulocytosis in 5–7
days
• Chronic blood loss –
• such as from the gastrointestinal tract or from
the gynecologic system
• may result in iron deficiency anemia.

2. Hemolytic anemias
• intravascular (IV) hemolysis
• extravascular (EV) hemolysis
 Sickle Cell Anemia
• The hemoglobinopathies are a group of
hereditary disorders caused by
inherited mutations that lead to
structural abnormalities in hemoglobin
• Sickle cell anemia, the prototypical (and
most prevalent) hemoglobinopathy,
stems from a mutation in the β-globin
gene that creates sickle hemoglobin
(HbS)
• Normal hemoglobins are tetramers
composed of two pairs of similar chains.
On average, the normal adult red cell
contains 96% HbA (α2β2), 3% HbA2
(α2δ2), and 1%Hb (HbF, α2γ2).
• HbS is produced by the substitution of
valine for glutamic acid at the sixth amino
acid residue of β-globin.
• In homozygotes, all HbA is replaced by
HbS, whereas in heterozygotes, only
about half is replaced
Incidence
• Sickle cell anemia is the most common familial
hemolytic anemia in the world.
• In parts of Africa where malaria is endemic, the gene
frequency approaches 30% as a result of a small but
significant protective effect of HbS against
Plasmodium falciparum malaria.
• In the United States, approximately 8% of blacks are
heterozygous for HbS, and about 1 in 600 have sickle
cell anemia
PATHOGENESIS
• On deoxygenation, HbS molecules form long polymers
by means of intermolecular contacts that involve the
abnormal valine residue at position 6.
• These polymers distort the red cell, which assumes an
elongated crescentic, or sickle, shape
• The sickling of red cells initially is reversible upon
reoxygenation.
• Over time, this cumulative damage creates irreversibly
sickled cells, which are rapidly hemolyzed.
Clinical Course
• Homozygous sickle cell disease usually is
asymptomatic until 6 months of age
• Hyperbilirubinemia and compensatory reticulocytosis
• From its onset, the disease runs an unremitting
course punctuated by sudden crises (vaso-occlusive,
or pain, crises.)
• vaso-occlusion most commonly occurs in the bone
marrow, where it often progresses to infarction.
Complications
• acute chest syndrome
• Stroke
• aplastic crisis triggered by parvovirus B19
infection
• infections
• With effective supportive care approximately
50% of patients survive beyond the fifth
decade.
• Treatment includes
– prophylaxis with penicillin
– A mainstay of therapy is hydroxyurea ( inhibitor of
DNA synthesis)
– Allogeneic bone marrow transplantation which
has the potential to be curative.
 MACROCYTIC ANEMIAS
• Megaloblastic anemia due to vitamin B12 (cobalamin)
deficiency
• Dietary deficiency is rare and usually seen only in strict
vegetarians
• Decreased absorption of vitamin B12 is more common and
may be caused by
– decreased intrinsic factor associated with gastrectomy or pernicious
anemia (an autoimmune gastritis);
– pancreatic insufficiency
– intestinal malabsorption due to parasites (fish tapeworm
[Diphyllobothrium latum]), bacteria (blind-loop syndrome), or
Crohn’s disease of the ileum.
• Clinically, B12 deficiency causes weakness due to
anemia
• sore (“beefy”) tongue due to generalized
epithelial atrophy.
• central nervous system effects
• Lab tests show low serum B12
• Treatment is intramuscular vitamin B12, which
will cause increased reticulocytes in about 5 days
• Megaloblastic anemia due to folate
deficiency can be caused by multiple
processes:
– Decreased intake in chronic alcoholics and the
elderly
– Decreased absorption in the upper small intestine
– Increased requirement for folate during
pregnancy and infancy
– Folate antagonists, e.g., methotrexate
• Clinically, folate deficiency produces
megaloblastic anemia without neurologic
disease symptoms
• Lab tests show low serum folate levels and
increased serum homocysteine.
• Treatment is folate replacement.
 POLYCYTHEMIA
• Increase in red blood cell mass
• POLYCYTHEMIA VERA
• caused by a clonal expansion of a multipotent
myeloid stem cell that primarily produces
extra erythrocytes
• myeloproliferative disorders
• SECONDARY POLYCYTHEMIA
• increased red cell mass due to compromised
ability of blood to supply oxygen to tissues
– chronic obstructive pulmonary disease
– cyanotic congenital heart disease.
– inappropriately high erythropoietin levels, with
renal cell carcinoma excreting erythropoietin
• RELATIVE POLYCYTHEMIA
• refers to an increased red cell count secondary
to decreased plasma volume (typically due to
dehydration)
• Red cell mass, erythropoietin, and blood
oxygen content are normal.