Disorders Affecting Red Blood Cells Flashcards
Iron-Deficiency Anemia (IDA)
ANEMIAS → MICROCYTIC – HYPOCHROMIC
● Etiology: Develops when the intake of iron is inadequate to meet a standard level of demand, when the need
for iron expands, when there is impaired absorption, or when there is chronic loss of hemoglobin.
● Laboratory Diagnosis:
o Anisocytosis
o Microcytosis
o Hypochromic
o Decreased hemoglobin
o Increased RDW
o Declining MCV, MCH, MCHC
o Usually suspected when the CBC findings show
hypochromic, microcytic anemia with elevated
RDW but no consistent shape changes to RBCs
o May see poikilocytosis, ovalocytes or target cells
o Serum ferritin and serum iron decreased, TIBC
increased
Anemia of Chronic Inflammation/Disease
ANEMIAS → MICROCYTIC – HYPOCHROMIC
- Etiology: Most common
anemia among hospitalized patients. The most significant cause of this anemia is
impaired ferrokinetics.
● Laboratory Diagnosis:
o Usually normocytic normochromic but microcytic hypochromic can develop and may represent coexistent iron deficiency
o Inflammatory condition may lead to leukocytosis, thrombocytosis or both
o MCV, MCHC normal or decreased
o RDW normal or increased
o Serum ferritin increased or normal, serum iron and TIBC decreased
Sideroblastic Anemia → Lead Poisoning
ANEMIAS → MICROCYTIC – HYPOCHROMIC
● Etiology: Lead interferes with porphyrin synthesis and iron storage in the mitochondria. It damages the
enzymes for hemoglobin synthesis leading to ineffective erythropoiesis.
● Laboratory Diagnosis:
o Usually normocytic normochromic but with chronic exposure will be microcytic hypochromic
o Reticulocyte count may be elevated in acute cases
o Coarse basophilic stippling
Hereditary Spherocytosis
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
- Etiology: usually inherited as a n autosomal dominant trait but can be recessive. They result from red blood
cell membrane abnormalities in spectrin, ankyrin, or protein 3, 4.1, or 4.2.
● Laboratory Diagnosis:
o Increased MCHC
o Normal to decreased MCV
o Normal MCH
o Osmotic fragility increased
o Hemoglobin and hematocrit normal or decreased
o Spherocytes, anisocytosis and poikilocytosis seen on smear
Hereditary Elliptocytosis
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
● Etiology: caused by a defect in one the skeletal proteins in the membrane. Membrane fragmentation causes a
decrease in cell surface and reduced cell deformability resulting in a shortened life span.
● Laboratory Diagnosis:
o Hemoglobin and hematocrit normal to decreased
o Mild elliptocytes or ovalocytes to severe fragmentation
Hereditary Stomatocytosis
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
● Etiology: Passive influx of sodium ions exceeds the loss of potassium ions causing the enzyme sodiumpotassium adenosine triphosphatase to be overwhelmed and the water content of the cell increases.
● Laboratory Diagnosis:
o Hemoglobin and hematocrit decreased
o MCHC decreased
o MCV increased
o Autohemolysis increased
o Stomatocytes present on smear
o Osmotic fragility increased
Paroxysmal Nocturnal Hemoglobinuria
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
● Etiology: Acquired hemolytic anemia due to a stem cell clonal mutation that causes the cell to lack
glycosylphosphatidylinositol-anchored proteins, including decay-accelerating factor and CD59, two proteins
that normally protect the RBC from complement activation and hemolysis. RBCs therefore have an increased
susceptibility to complement, which results in intravascular hemolysis and hemoglobinuria that occur in
irregular episodes, especially during sleep.
● Laboratory Diagnosis:
o Hemoglobinemia, hemoglobinuria, decreased level of serum haptoglobin
o Increased levels of indirect bilirubin, lactate dehydrogenase
Paroxysmal Cold Hemoglobinuria
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
● Etiology: Acquired hemolytic anemia due to a stem cell clonal mutation that causes the cell to lack
glycosylphosphatidylinositol-anchored proteins, including decay-accelerating factor and CD59, two proteins
that normally protect the RBC from complement activation and hemolysis. RBCs therefore have an increased
susceptibility to complement, which results in intravascular hemolysis and hemoglobinuria that occur in
irregular episodes, especially during sleep.
● Laboratory Diagnosis:
o Hemoglobinemia, hemoglobinuria, decreased level of serum haptoglobin
o Increased levels of indirect bilirubin, lactate dehydrogenase
Paroxysmal Cold Hemoglobinuria
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
* Etiology: Rare acquired autoimmune hemolytic anemia in which the Donath-Landsteiner autoantibody (AntiP) binds RBCs during exposure to cold, producing acute hemolysis and hematuria upon warming. Full
complement activation and hemolysis occur only upon warming up.
* Laboratory Diagnosis:
o Reticulocytosis
o Polychromasia and spherocytes
o Schistocytes, nRBCs, anisocytosis, poikilocytosis, erythrophagocytosis may be seen
o Leukopenia followed by leukocytosis occurs
o DAT is usually positive for C3d only
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
Major function of G6PD is to keep hemoglobin
iron in the reduced, physiologically active (ferrous) state for oxygen transport and to protect hemoglobin from
oxidative damage. G6PD-deficient RBCs cannot generate sufficient NADPH to reduce glutathione, and thus
cannot effectively detoxify the hydrogen peroxide produced upon exposure to oxidative stress resulting in
oxidation of membrane thiols and hemoglobin.
o Laboratory Diagnosis:
§ Morphology is normal except during a hemolytic episode
§ Anisocytosis, poikilocytosis, sperocytosis, schistocytes may occur
§ Increased reticulocytes
§ Serum haptoglobin decreased, hemoglobinemia, hemoglobinuria
§ Elevated indirect bilirubin
§ WBC count slightly elevated
Pyruvate Kinase Deficiency (PKD)
HEMOLYTIC ANEMIAS → NORMOCYTIC – NORMOCHROMIC
PK catalyzes the conversion of phosphoenolpyruvate to pyruvate to
form ATP. Consequences of PKD are ATP depletion and an increase in 2,3-bisphosphoglycerate (2,3-BPG),
which shifts the hemoglobin-oxygen dissociation curve to the right and decreases oxygen affinity of
hemoglobin. This promotes greater release of oxygen to the tissues and enables affected individuals to tolerate
lower levels of hemoglobin.
o Laboratory Diagnosis:
§ Anisocytosis, poikilocytosis,
polychromasia
§ Burr cells
§ Post-splenectomy may show HowellJolly bodies, Pappenheimer bodies, and
target cells
§ WBC and platelet counts are normal or
slightly increased
§ Increased indirect bilirubin, decreased
serum haptoglobin
Autoimmune Hemolytic Anemia (AIHA)
● Etiology: destruction of RBCs by antibodies
produced by the patient. Can be seen in Hemolytic
Disease of the newborn, acquired autoimmune
hemolytic anemia, or incompatible transfusion.
● Laboratory Diagnosis:
o Hemoglobin and hematocrit decreased
o MCV, MCHC are normal (MCV can be
increased if prominent reticulocytosis)
o Spherocytes, nucleated RBCs, macrocytes,
polychromasia seen on smear
o Elevated WBCs due to increase in neutrophils
Non-immune Hemolytic Anemia
Etiology: Intravascular or extravascular hemolysis. Can be caused by thermal injury or mechanical
injury.
● Laboratory Diagnosis:
o In thermal injury: Increased WBCs, microspherocytes, budding of membrane
o In mechanical injury: schistocytes, keratocytes, increased reticulocytes
o In both: Hemoglobin and hematocrit normal or decreased
Microangiopathic Hemolytic Anemia (MAHA)
● Etiology: Clinical features are: Intravascular hemolysis, TTP, HUS, DIC, HELLP, HIV. MAHA is caused
by fibrin strands bridging arteriolar lumen when supplying blood to inflamed or neoplastic tissue,
which lop off fragments of RBCs whose membranes seal leaving distorted cells. In TTP, small platelet
thrombi occlude capillaries and arterioles.
● Laboratory Diagnosis:
o Platelets are decreased
o Hemoglobin and hematocrit are decreased
o MCV, MCHC are normal
o Increased reticulocytes
o Schistocytes, polychromasia seen on film
Sickle Cell Anemia (Hemoglobin SS Disease)
- Etiology: Defined by the amino acid substitution of glutamic acid being replaced by valine on the beta chain at
the sixth position. Reversible sickle cells circulate as normal biconcave discs when fully oxygenated but
undergo hemoglobin polymerization, show increased viscosity, and change shape on deoxygenation.
Irreversible sickle cells do not change their shape regardless of the change in oxygen tension or degree of
hemoglobin polymerization. These cells are seen on the peripheral smear. - Laboratory Diagnosis:
o Sickle cells, marked poikilocystosis, anisocytosis, target cells, nRBCs
o Few spherocytes, basophilic stippling, Pappenheimer bodies, Howell-Jolly bodies may be seen
o Moderate to marked polychromasia
o Moderate leukocytosis with neutrophilia
o Thrombocytosis
o Insolubility can be detected by mixing 1 drop blood with 1 drop 2% sodium metabisulfite on slide and
seal with coverslip. The hemoglobin is reduced to deoxygenated form, which induces polymerization
and result in sickle cell formation. Positive result is turbid due to decreased solubility of Hb S.
o Hemoglobin electrophoresis, high-performance liquid chromatography, or capillary electrophoresis
can also be used
Hemoglobin C
Hemoglobin C
* Etiology: Defined by the amino acid substitution of glutamic acid
being replaced by lysine on the beta chain at the sixth position. It
is a milder disease than Hb S. HbC polymerizes under low oxygen
tension, but the structure of the polymers differs. HbS polymers
are long and thin, whereas the polymers in Hb C form short, thick crystal within the RBCs and do not alter the
shape.
* Laboratory Diagnosis:
o Microcytosis and mild hypochromasia occasionally occurs
o Marked increase in target cells
o Slight to moderate increase in reticulocytes
o nRBCs may be present
o Many crystals appear extracellularly with no evidence of cell membran
Hemoglobin SC Disease
Etiology: Defined by the amino acid substitutions on each of the beta chains (Glutamic acid by valine (Hb S),
and glutamic acid by lysine (Hb C)). Resembles a mild sickle cell disease.
* Laboratory Diagnosis:
o Increased hemoglobin
o Few sickle cells, target cells, intraerythrocytic crystalline structures (cell aggregates protrude from
membrane). SC crystals are longer than Hb C but shorter and thicker than Hb S.
o Positive hemoglobin solubility test
Unstable Hemoglobins
- Etiology: Result from genetic mutations to globin genes creating hemoglobin products that precipitate in vivo,
producing Heinz bodies and causing hemolytic anemia. - Laboratory Diagnosis:
o RBC morphology may be normal or slight hypochromia and basophilic stippling
o Reticulocytosis persists after splenectomy
o Isopropanol can be added at 37OC to weaken bonding forces of the hemoglobin molecule. Unstable
hemoglobins will precipitate in 5 minutes. Normal hemoglobin does not precipitate until 40 minutes.
Hemoglobin S/ β-Thalassemia
- Resembles mild or moderate sickle cell anemia. There is a greater amount of Hb S than Hb A, increased levels
of A2 and Hb F, microcytosis, hemolytic anemia, abnormal morphology, and splenomegaly can distinguish this
from sickle cell trait.
