Anemias

Dr. Claudia Cladovan

APPROACH TO THE CHILD

WITH ANEMIA

Finding the cause is always important even

though anemia in childhood has many
causes
The cause is suggested by a careful history
Nutritional causes should be addressed by
inquiry about

dietary intake,
growth and development,
symptoms of chronic disease,
malabsorption,
or blood loss

APPROACH TO THE CHILD

WITH ANEMIA

Hemolytic disease may be suggested by

a history of jaundice (including neonatal jaundice)
or by a family history of anemia, jaundice, gallbladder
disease, splenomegaly, or splenectomy

The child's ethnic background may suggest the

possibility of
certain hemoglobinopathies
or of deficiencies of red cell enzymes such as glucose-6phosphate dehydrogenase (G6PD)

The age of the patient is important

iron deficiency anemia and beta-globin disorders present
more commonly between 6 and 24 months of age

APPROACH TO THE CHILD

WITH ANEMIA

The physical examination may also reveal clues to

the cause of anemia.
Poor growth may suggest chronic disease or
hypothyroidism.
Congenital anomalies may be associated with constitutional
aplastic anemia (Fanconi's anemia) or with constitutional
hypoplastic anemia (Diamond-Blackfan anemia).
Other disorders may be suggested by the findings of
petechiae or purpura (leukemia, aplastic anemia, hemolytic
uremic syndrome),
jaundice (hemolysis or liver disease),
generalized lymphadenopathy (leukemia, juvenile rheumatoid
arthritis, HIV infection),
splenomegaly (leukemia, sickle syndromes, hereditary
spherocytosis, liver disease, hypersplenism),
or evidence of chronic or recurrent infections.

APPROACH TO THE CHILD

WITH ANEMIA

The initial laboratory evaluation of the anemic

child generally consists of
a complete blood count (CBC) with differential and
platelet count,
review of the peripheral blood smear,
and usually a reticulocyte count.

The diagnostic scheme depends principally on

the MCV to determine whether the anemia is
microcytic,
normocytic,
or macrocytic.

APPROACH TO THE CHILD

WITH ANEMIA
Microcytic

anemias

iron deficiency is an important cause of

microcytic anemia, especially between 6
and 24 months of age
a trial of therapeutic iron is appropriate
in such children
if a trial of therapeutic iron fails to
correct the anemia and microcytosisthen further laboratory evaluation is
required.

APPROACH TO THE CHILD

WITH ANEMIA

Reticulocyte count and the peripheral blood smear

determine whether a normocytic or macrocytic anemia is
due to hemolysis.
hemolytic disease is associated with an elevated
reticulocyte count
review of the peripheral smear for evidence of hemolysis
(eg, spherocytes, red cell fragmentation, sickle forms) is
important in the evaluation of children with normocytic
anemias and low reticulocyte counts

Autoimmune hemolysis can be excluded by

Coombs' testing
Review of blood counts and the peripheral smears
of the mother and father may suggest congenital
disorders such as hereditary spherocytosis

APPROACH TO THE CHILD

WITH ANEMIA

Children with normocytic or macrocytic anemias,

with relatively low reticulocyte counts and no
evidence of hemolysis on the blood smear, usually
have anemias caused by inadequate erythropoiesis
in the bone marrow.
presence of neutropenia or thrombocytopenia in such
children suggests bone marrow failure and the possibility
of aplastic anemia or malignancy
usually dictates examination of the bone marrow

Pure red cell aplasia may be

constitutional (Diamond-Blackfan anemia),

acquired and transient (transient erythroblastopenia of
childhood),
a manifestation of a systemic disease such as renal
disease or hypothyroidism,
or due to malnutrition or deficiencies of folate or
cobalamin

PURE RED CELL APLASIA

CONGENITAL HYPOPLASTIC ANEMIA
(Diamond-Blackfan Anemia)

General

Considerations

Rare cause of anemia presents in

infancy or early childhood.
The cause of the disorder is unclear, and
both autosomal dominant and
autosomal recessive modes of
inheritance have been suggested.

PURE RED CELL APLASIA

CONGENITAL HYPOPLASTIC ANEMIA
(Diamond-Blackfan Anemia)

Clinical

Findings
A. Symptoms and Signs:
chronic anemia, such as pallor, and
congestive heart failure
short stature or other congenital
anomalies are present in 1/3 patients.
variety of anomalies have been described,
and those affecting the head, face, and
thumbs are probably the most common.

PURE RED CELL APLASIA

CONGENITAL HYPOPLASTIC ANEMIA
(Diamond-Blackfan Anemia)

B. Laboratory Findings:

severe anemia
marked reticulocytopenia
neutrophil count is usually normal or slightly
decreased,
platelet count is normal or elevated.
bone marrow usually shows a marked decrease
in erythroid precursors but is otherwise normal.
levels of fetal hemoglobin are usually increased
and there is evidence of persistent fetal
erythropoiesis
the level of adenosine deaminase in
erythrocytes is elevated.

PURE RED CELL APLASIA

CONGENITAL HYPOPLASTIC ANEMIA
(Diamond-Blackfan Anemia)

Treatment
Oral corticosteroids should be initiated as soon as
the diagnosis of Diamond-Blackfan anemia is made
prednisone, 2 mg/kg/d,

Chronic red cell transfusion therapy inevitably

causes hemosiderosis and the need for chelation
with parenteral deferoxamine.
Bone marrow transplantation is an alternative
therapy
Hematopoietic growth factors have been used in
some cases with limited success.

Unpredictable, spontaneous remissions

occasionally occur.

NUTRITIONAL ANEMIAS
IRON DEFICIENCY ANEMIA

General Considerations
Normal term infants are born with sufficient iron stores to
prevent iron deficiency for the first 4 months of life.
Thereafter, enough iron needs to be absorbed to keep pace
with the needs of rapid growth.
For this reason, nutritional iron deficiency is most common
between 6 and 24 months of life.
A deficiency earlier than 6 months of age may occur if iron
stores at birth are reduced by

prematurity,
small birth weight,
neonatal anemia,
or perinatal blood loss or if there is subsequent iron loss due to
hemorrhage.

Iron-deficient children older than 24 months of age should be

investigated for blood loss.

NUTRITIONAL ANEMIAS
IRON DEFICIENCY ANEMIA
Clinical

Findings
A. Symptoms and Signs:
Mild iron deficiency is usually asymptomatic.
In infants with more severe iron deficiency,
pallor, fatigue, irritability, and delayed motor
development are common.
Children whose iron deficiency is due in part
to ingestion of unfortified cow's milk may be
fat and flabby, with poor muscle tone.
A history of pica is common.

NUTRITIONAL ANEMIAS
IRON DEFICIENCY ANEMIA

Clinical Findings
B. Laboratory Findings:
The severity of anemia depends on the degree of iron
deficiency, and the hemoglobin may be as low as 3-4 g/dL in
severe cases.
Red cells are microcytic and hypochromic with a low MCV and
low MCH.
The reticulocyte count is usually normal but may be slightly
elevated in severe cases.
Iron studies show

a decreased serum ferritin

low serum iron,
elevated total iron-binding capacity,
and decreased transferrin saturation.
free erythrocyte protoporphyrin is elevated.

The bone marrow examination is not helpful in the diagnosis

NUTRITIONAL ANEMIAS
IRON DEFICIENCY ANEMIA

Treatment

oral dose of elemental iron is 4-6 mg/kg/d in three

divided daily doses.
mild cases may be treated with 3 mg/kg/d given once
daily before breakfast.
parenteral administration of iron is rarely necessary.
Iron therapy results in
an increased reticulocyte count within 3-5 days, which is
maximal between 5 and 7 days.
hemoglobin level begins to increase thereafter.
moderate to severe cases, an elevated reticulocyte count 1
week after initiation of therapy confirms the diagnosis
iron deficiency is the only cause of anemia, adequate
treatment usually results in a resolution of the anemia within
4-6 weeks.
Treatment is generally continued for a few additional months
to replenish iron stores.

NUTRITIONAL ANEMIAS
MEGALOBLASTIC ANEMIAS

General Considerations
Megaloblastic anemia is a macrocytic anemia caused
by deficiency of cobalamin (vitamin B12), folic acid, or
both.
Cobalamin deficiency due to dietary insufficiency may
occur in
infants who are breast-fed by mothers who are strict
vegetarians or who have pernicious anemia.
intestinal malabsorption occurs with Crohn's disease, chronic
pancreatitis, bacterial overgrowth of the small bowel, or after
surgical resection of the terminal ileum.
deficiencies due to inborn errors of metabolism
(transcobalamin II deficiency, methylmalonic aciduria) have
also been described.
malabsorption of cobalamin due to deficiency of intrinsic
factor (pernicious anemia) is rare in childhood.

NUTRITIONAL ANEMIAS
MEGALOBLASTIC ANEMIAS

General Considerations
Folic acid deficiency may be caused by

inadequate dietary intake, in severely

malnourished infants ,in infants fed goat's milk
not fortified with folic acid.
malabsorption,

malabsorptive syndromes such as celiac disease

anticonvulsant medications (eg, phenytoin and
phenobarbital) and cytotoxic drugs (eg, methotrexate)
have also been associated with folate deficiency, caused
by interference with folate absorption or metabolism

increased folate requirements, during infancy

because of rapid growth and also in children with
chronic hemolytic anemia
or some combination of the three.

NUTRITIONAL ANEMIAS
MEGALOBLASTIC ANEMIAS

Clinical Findings
A. Symptoms and Signs:
Infants with megaloblastic anemia may show pallor
and mild jaundice due to ineffective erythropoiesis.
Classically, the tongue is smooth and beefy red.
Infants with cobalamin deficiency may be irritable
and may be poor feeders.
Older children with cobalamin deficiency may
complain of paresthesias, weakness, or an
unsteady gait and may show decreased vibratory
sensation and proprioception on neurologic
examination.

NUTRITIONAL ANEMIAS
MEGALOBLASTIC ANEMIAS

Clinical Findings
B. Laboratory Findings:

an elevated MCV and mean corpuscular hemoglobin (MCH).

blood smear shows numerous macro-ovalocytes with anisocytosis
and poikilocytosis.
Neutrophils are large and have hypersegmented nuclei.
The white cell count and the platelet count are normal with mild
deficiencies, but may be decreased in more severe cases.
Examination of the bone marrow typically shows erythroid
hyperplasia with large erythroid and myeloid precursors.

There is nuclear-cytoplasmic dissociation and ineffective erythropoiesis.

The serum indirect bilirubin concentration may be slightly elevated.

Children with cobalamin deficiency have a low serum vitamin B12
level.
In addition, the urinary concentration of methylmalonic acid is
significantly elevated.
Assessment of folate stores is best done by measuring the level of
red cell folate

NUTRITIONAL ANEMIAS
MEGALOBLASTIC ANEMIAS

Treatment
Treatment of cobalamin deficiency due to
inadequate dietary intake
Is readily accomplished with oral supplementation.
Most cases, however, are due to intestinal malabsorption
and require parenteral treatment.
In severe cases, parenteral therapy may induce lifethreatening hypokalemia and require supplemental
potassium.

Folic acid deficiency

Is effectively treated with oral folic acid in most cases.
Children at risk for the development of folic acid
deficiencies such as premature infants and those with
chronic hemolysis are usually given supplementary folic
acid prophylactically

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
General

considerations
The congenital hemolytic anemias are
usually divided into three categories:
defects of the red cell membrane,
hemoglobinopathies,
and disorders of red cell metabolism.
Hereditary

spherocytosis and
elliptocytosis are the most common
red cell membrane disorders

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
HEREDITARY SPHEROCYTOSIS

General Considerations
Is a relatively common inherited hemolytic anemia
The hallmark of hereditary spherocytosis is the
presence of microspherocytes in the peripheral
blood.
The disease is inherited in an autosomal dominant
fashion in about 80% of cases; the remainder are
thought to be autosomal recessive or to be caused
by new mutations.
Hereditary spherocytosis is the result of a partial
deficiency of spectrin. an important structural
protein of the red cell membrane skeleton

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
HEREDITARY SPHEROCYTOSIS

Clinical Findings
A. Symptoms and Signs:

Symptoms and signs of hereditary spherocytosis are

those related to hemolytic anemia.
Significant hyperbilirubinemia in the newborn period.
Splenomegaly subsequently develops in the majority
and is usually present by the age of 5 years.
Jaundice is variably present and in many patients may
only be noted during infection.
Patients with significant chronic anemia may complain of
pallor, fatigue, or malaise.
Intermittent exacerbations of the anemia are caused by
increased hemolysis or by aplastic crises and may be
associated with severe weakness, fatigue, fever,
abdominal pain, or even congestive heart failure.

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
HEREDITARY SPHEROCYTOSIS
Clinical

Findings
A. Symptoms and Signs:
Complications
Severe jaundice may occur in the neonatal
period and, if not controlled by phototherapy,
may occasionally require exchange transfusion.
Splenectomy is. associated with an increased
risk of overwhelming bacterial infections,
particularly with pneumococci.
Gallstones occur in 60-70% of adults who have
not undergone splenectomy and may form as
early as 8-10 years of age.

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
HEREDITARY SPHEROCYTOSIS

Clinical Findings
B. Laboratory Findings:

Most patients have mild chronic hemolysis with hemoglobin values

between 9 and 12 g/dL.
In some cases, the hemolysis is fully compensated and the
hemoglobin is in the normal range.
Rare cases of severe disease require frequent transfusions.
The anemia is usually normocytic and hyperchromic, and many
patients have an elevated MCHC.
The blood smear shows numerous microspherocytes and
polychromasia.
The reticulocyte count is elevated and is often higher than might
be expected for the degree of anemia.
White blood cells and platelets are usually normal.
The osmotic fragility is increased, particularly after incubation at
37C for 24 hours.
Serum bilirubin usually shows an elevation in the unconjugated
fraction.
Coombs' testing is negative.

CONGENITAL HEMOLYTIC ANEMIAS:

RED CELL MEMBRANE DEFECTS
HEREDITARY SPHEROCYTOSIS

Treatment
Supportive measures include the administration of
folic acid to prevent the development of red cell
hypoplasia due to folate deficiency.
Acute exacerbations of anemia due to increased
rates of hemolysis or to aplastic crises due to
infection with human parvovirus may be severe
enough to require red cell transfusions.
Splenectomy is performed in many cases and
always results in significant improvement.
All patients scheduled for splenectomy should be
immunized with pneumococcal vaccine prior to
the procedure

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES

General considerations
The hemoglobinopathies are generally classified
into two major groups.
The first, the thalassemias, are caused by
quantitative deficiencies in the production of
globin chains.
These quantitative defects in globin synthesis result in a
microcytic and hypochromic anemia.

The second group of hemoglobinopathies are

those caused by structural abnormalities of globin
chains.
The most important of these, hemoglobins S, C, and E,
are all the result of point mutations and single amino
acid substitutions in the globin.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ALPHA-THALASSEMIA
General Considerations
Most of the -thalassemia syndromes
are the result of deletions of one or more
of the alpha-globin genes on
chromosome 16.
Normal diploid cells have four alphaglobin genes, and thus the variable
severity of the alpha-thalassemia
syndromes is related to the number of
gene deletions.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ALPHA-THALASSEMIA

Clinical Findings
The clinical findings depend upon the number of alpha-globin
genes deleted.
Persons with three alpha-globin genes (one-gene deletion) are
asymptomatic and have no hematologic abnormalities.

Hemoglobin levels and MCV are normal.

Hemoglobin electrophoresis in the neonatal period shows 1-3% Bart
hemoglobin, a variant hemoglobin composed of four gamma-globin
chains.
Hemoglobin electrophoresis after the first few months of life is
normal.

Persons with two alpha-globin genes (two-gene deletion) are

typically asymptomatic.

The MCV is usually less than 100 fL at birth.

Hematologic studies in older infants and children show a normal or
slightly decreased hemoglobin level with a low MCV and a slightly
hypochromic blood smear with some target cells.
The hemoglobin electrophoresis typically shows 5-10% Bart
hemoglobin in the neonatal period but is normal in older children
and adults.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ALPHA-THALASSEMIA

Clinical Findings
Persons with one alpha-globin gene (three-gene
deletion)

have a moderately severe microcytic hemolytic anemia (Hb 710 g/dL),

often accompanied by hepatosplenomegaly and some bony
abnormalities caused by the expanded medullary space.
reticulocyte count is elevated,
and the red cells show marked hypochromia and microcytosis
with significant poikilocytosis and some basophilic stippling.
Hemoglobin electrophoresis in the neonatal period typically
shows 15-25% Bart hemoglobin.
Later in life, hemoglobin H (composed of four alpha-globin
chains) is detected and may make up as much as 20-30% of the
hemoglobin.
Incubation of red cells with brilliant cresyl blue (hemoglobin H
preparation) shows inclusion bodies formed by denatured
hemoglobin H.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ALPHA-THALASSEMIA
Clinical

Findings
The deletion of all four alpha-globin genes
causes severe intrauterine anemia and asphyxia
results in hydrops fetalis and fetal demise or
neonatal death shortly following delivery.
There is extreme pallor and massive
hepatosplenomegaly.
Hemoglobin electrophoresis reveals a
predominance of Barts hemoglobin with a
complete absence of normal fetal or adult
hemoglobin.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ALPHA-THALASSEMIA

Treatment
Asymptomatic persons require no treatment.
Those with hemoglobin H disease should receive
supplemental folic acid and avoid the oxidant drugs
that cause hemolysis.
The anemia may also be exacerbated during periods
of infection, and transfusions may be required.
Occasionally, infants with hemoglobin H disease may
show failure-to-thrive without red cell transfusions.
Hypersplenism may develop later in childhood and
require surgical splenectomy.
Genetic counseling and prenatal diagnosis should be
offered to families at risk for children with hemoglobin
H disease or fetal hydrops.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

General Considerations
In contrast to the four alpha-globin genes, only two betaglohin genes are present in diploid cells, one on each
chromosome 11.
Some beta -thalassemia genes produce no beta-globin chains
and are termed beta0- thalassemia.
Other beta -globin genes produce some beta -globin but in
diminished quantities and are termed beta+-thalassemia.
Persons affected by beta -thalassemia may be heterozygous
or homozygous.
Heterozygotes for most beta-thalassemia genes have betathalassemia minor.
Most homozygotes have beta-thalassemia major (Cooley's
anemia), which is a severe transfusion-dependent anemia.
Other homozygotes have a condition known as thalassemia
intermedia that is more severe than thalassemia minor but
not generally transfusion-dependent.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

Clinical Findings
A. Symptoms and Signs:
Persons with beta-thalassemia minor are usually
asymptomatic with a normal physical examination.
Those with beta-thalassemia major are normal at
birth but develop a significant anemia during the first
year of life as fetal hemoglobin production decreases.

If the disorder is not identified and treated with blood

transfusions, such children develop massive
hepatosplenomegaly and enlargement of the medullary
space with thinning of the bony cortex.
The skeletal changes cause characteristic facial deformities
(prominent forehead and maxilla) and predispose the child to
pathologic fractures.
Inadequate treatment causes poor growth and development
in these children.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

Clinical Findings
B. Laboratory Findings:
Laboratory findings in beta-thalassemia
minor include a normal or modestly
decreased hemoglobin level.
The MCV is almost always decreased.
The blood smear typically shows hypochromia,
target cells, and sometimes basophilic stippling.
Hemoglobin electrophoresis is usually diagnostic
when hemoglobin A2 or hemoglobin F or both is
elevated.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

Clinical Findings
Infants with beta-thalassemia major are
hematologically normal at birth but develop
severe anemia after the first few months of life.
The blood smear typically shows a severe
hypochromic, microcytic anemia with marked
anisocytosis and poikilocytosis.
Target cells are prominent, and nucleated red blood
cells often exceed the number of circulating white
blood cells.
The hemoglobin usually falls to 5-6 g/dL or less, and
the reticulocyte count is significantly elevated.
Platelet and white blood cell counts may be
increased,
The serum bilirubin is elevated.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

Clinical Findings
Infants with beta-thalassemia major
The bone marrow shows marked erythroid
hyperplasia but is rarely needed for diagnosis.
Hemoglobin electrophoresis shows only fetal and
A2 hemoglobin in children with homozygous
beta-thalassemia.
Those with beta +-thalassemia genes make
some hemoglobin Al but have a marked increase
in fetal and in A2 hemoglobin.
The diagnosis of homozygous beta-thalassemia
may also be suggested by the finding of betathalassemia minor in both parents.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
BETA-THALASSEMIA

Treatment
Beta-thalassemia minor requires no specific therapy but has
important implications for genetic counseling.
For those with beta-thalassemia major, two approaches to
treatment are now available:

chronic transfusion with iron chelation or bone marrow

transplantation.
Programs of blood transfusion are generally targeted to maintain
a nadir hemoglobin level above 11 g/dL.
However, maintenance of good health currently requires iron
chelation with nightly subcutaneous infusion of deferoxamine.
Small doses of supplemental ascorbic acid may enhance the
efficacy of iron chelation.
Patients on chronic transfusion programs generally develop
hypersplenism and require splenectomy
Bone marrow transplantation is an important therapeutic option
for children with beta -thalassemia major

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY
General considerations
Erythrocytes are dependent on the anaerobic
metabolism of glucose for the maintenance
of adenosine triphosphate (ATP) levels
sufficient for normal homeostasis.
Congenital deficiencies of many (not all)
glycolytic pathway enzymes have been
associated with hemolytic anemias.
In general, the morphologic abnormalities
present on the blood smear are nonspecific,
and the inheritance of these disorders is
autosomal recessive or X-linked.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY

General considerations
Thus, the possibility of a red cell enzyme defect
should be considered during the evaluation of a
congenital hemolytic anemia when
the blood smear does not show red cell morphology
typical of membrane or hemoglobin defects (eg,
spherocytes, sickle forms, target cells),
when hemoglobin disorders are excluded by
hemoglobin electrophoresis
and when family studies do not suggest an
autosomal dominant disorder.
The diagnosis is confirmed by finding a low level of
the deficient enzyme.
G6PD deficiency and pyruvate kinase deficiency

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY

Clinical Findings
A. Symptoms and Signs:
Infants with G6PD deficiency may have significant
hyperbilirubinemia and may require the use of
phototherapy or exchange transfusion
Older children with G6PD deficiency are asymptomatic
and appear normal between episodes of hemolysis.
Hemolytic episodes are often triggered by infection or
by the ingestion of oxidant drugs, antimalarial
compounds and sulfonamide antibiotics.
Ingestion of fava beans may trigger hemolysis in
Mediterranean and Asian children
Episodes of hemolysis are associated with pallor,
jaundice, hemoglobinuria, and sometimes
cardiovascular compromise.

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY

Clinical Findings
B. Laboratory Findings:
The hemoglobin, reticulocyte count, and blood smear are
usually normal in the absence of oxidant-induced hemolysis.
Episodes of hemolysis are associated with a variable fall in
hemoglobin.
"Bite" cells or blister cells may be seen, along with a few
spherocytes.
Hemoglobinuria is common, and the reticulocyte count
increases within a few days.
Heinz bodies may be demonstrated with appropriate stains.
The diagnosis is confirmed by the finding of reduced levels of
G6PD in erythrocytes.
Because this enzyme is present in increased quantities in
reticulocytes, the test is best performed at a time when the
reticulocyte count is normal or near normal

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY

Clinical Findings
Some common drugs and chemicals that can
induce hemolytic anemia in persons with G6PD
deficiency.

Acetanilid
Niridazole
Doxorubicin
Nitrofurantoin
Furazolidone
Phenazopyridine
Methylene blue
Primaquine
Nalidixic acid
Sulfamethoxazole

CONGENITAL HEMOLYTIC ANEMIAS:

HEMOGLOBINOPATHBES
ENTYMES DEFICIENCY

Treatment
The most important issue is avoidance of drugs
known to be associated with hemolysis.
For some Mediterranean and Asian patients, the
consumption of fava beans must also be avoided.
Infections should be treated promptly and
antibiotics given when appropriate.
Most episodes of hemolysis are self-limiting, but
red cell transfusions may be lifesaving when signs
and symptoms indicate cardiovascular
compromise.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

General Considerations
Acquired autoimmune hemolytic anemia is
more common causes of acute anemia
after the first year.
It may arise as

an isolated problem
or may complicate
an infection (hepatitis, upper respiratory tract
infections, mononucleosis, cytomegaloviras infection),
systemic lupus erythematosus
other autoimmune syndromes
or immunodeficiency states.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

Clinical Findings
A. Symptoms and Signs:

The disease usually has an acute onset,

presenting with weakness, pallor, and fatigue.
Jaundice is a prominent finding, and
splenomegaly is often present.

Some cases are chronic and insidious in

onset.
Clinical evidence of the underlying
disease may be present.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

B. Laboratory Findings:

The anemia is normochromic and normocytic and may vary

from mild to severe (hemoglobin concentration <5 g/dL).
The reticulocyte count is usually increased but occasionally
may be normal or low.
Spherocytes and nucleated red cells may be seen on the
peripheral smear.
Although leukocytosis and elevated platelet counts are a
common finding, thrombocytopenia is occasionally seen.
Other laboratory data consistent with hemolysis are present
such as increased indirect and total bilirubin, lactic
dehydrogenase (LDH), aspartate transaminase (AST), and
urinary urobilinogen.

The hemolysis is intravascular if there is hemoglobinemia or

hemoglobinuria.
Examination of bone marrow shows a marked erythroid
hyperplasia.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

B. Laboratory Findings:
Serologic studies provide important information
In almost all cases the direct and indirect antiglobulin
(Coombs') test are positive.
Further evaluation allows distinction of three syndromes.
The presence of IgG, maximal in vitro activity at 37C, and
either no antigen specificity or an Rh-like specificity
constitute warm autoimmune hemolytic anemia with
extravascular destruction by the reticuloendothelial system.
The detection of complement alone and optimal reactivity in
vitro at 4C with i antigen specificity are diagnostic of cold
autoimmune hemolytic anemia with intravascular hemolysis.
Paroxysmal cold hemoglobinuria appears identical with cold
autoimmune hemolytic anemia but has a different antigen
specificity and exhibits hemolysis as well as agglutination in
vitro.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

Treatment
Most patients with warm autoimmune hemolytic
anemia (in which hemolysis is extravascular)
respond the prednisone.
Patient may respond to 2 g of intravenous immune
globulins (IGIV) per kilogram for 1-3 days, but fewer
patient respond to IGIV than to prednisone.
Although the rate of remission with splenectomy
may be as high a 50%, particularly in warm
autoimmune hemolytic anemia, this approach should
be withheld until other treatments have been tried.
In severe cases unresponsive to more conventional
therapy, immunosuppressive agents such as
cyclophosphamide, azathioprine or busulfan may be
tried alone or in combination with corticosteroids.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

Treatment
Patients with cold autoimmune hemolytic
anemia and paroxysmal cold
hemoglobinuria are less likely the respond
to corticosteroids or IGIV.
Since both of these syndromes are most apt to
be associated with infections and have an acute,
self-limited course, supportive care may be all
that is required.
Plasma exchange is effective in cold autoimmune
(IgM) hemolytic anemia (and may be helpful in
severe cases) because the offending antibody
has only an intravascular distribution.

ACQUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIA

Treatment
Supportive therapy is crucial.
Patients with cold-reacting antibodies, particularly
paroxysmal cold hemoglobinuria, should be kept
in a warm environment.
Transfusion may be necessary because of the
complications of severe anemia but should be
used only when there is no alternative.
Patients with severe intravascular hemolysis may
have associated disseminated intravascular
coagulation (DIC), and heparin therapy should be
considered in such cases.