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Anemia
Anemia

Definition. It is an abnormal decrease in
the number of circulating RBCs, Hb conc.,
and hematocrit (PCV). It is not a disease
itself but is a symptom of another disorder.
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It is important to consider the following
developmental variations when evaluating
an infant or child for anemia:
1-Hb level and PCV are relatively high in the
newborn; these values subsequently decline,
reaching a nadir at approximately 7 weeks of
age for the premature infant and at 2 - 3 ms of
age for the term infant. (This condition is referred
to as the “physiologic anemia” of infancy or
anemia of prematurity) .
Total Hb concentration and hematocrit rise
gradually during childhood .
Normal values in children
Age
Hb(g/dl)
Retic.%
cord blood
14-22
5-7
2week
13-20
1
3 month
9.5-14.5
1
6 m- 6yr
7-12 yr
10.5-14.5
11-16
1
1
Adult male
12-16
1.6
Adult female
14-18
1.6
2-Hb F is the major Hb of prenatal and early
postnatal life.
At cord blood ,Hb F values approached 70% then
it decline postnatally; by 9 to 12 months of age,
the Hb F values represent <2% of the total Hb
concentration.
3-Mean corpuscular volume (MCV) is relatively
high during the neonatal period but declines during
the latter part of infancy.
The MCV is lowest during infancy, gradually
increasing with age during childhood, reaching
adult levels during adolescence.
Classification
In clinical practice, anemias are classified
according to the morphologic appearance (i.e.,
color and size) of RBC on peripheral smear as
well as the MCV.
1-Hypochromic, microcytic (small, pale
RBCs; a low MCV)
2-Macrocytic (large RBCs; a high MCV)
3-Normochromic, normocytic (cells of normal
size and shape; a normal MCV)
Hypochromic, microcytic
anemias
Defect. Hypochromic, microcytic RBCs indicate
impaired synthesis of the heme or globin
components of Hb.
Defective heme synthesis may be the
result of iron deficiency, lead poisoning,
chronic inflammatory disease, pyridoxine
deficiency, sideroblastic anemia, or copper
deficiency.
Defective globin synthesis is characteristic
of the thalassemia syndromes.
Evaluation. Laboratory studies that are useful
in evaluating the hypochromic, microcytic
anemia
1- Serum ferritin
2-Total s. iron-binding capacity.
3- Soluble transferrin receptor (sTR).
4- Quantitative measurements of the Hb A1 ,
Hb A2 and Hb F levels.
Normal
Hypochromic microcytic
Iron deficiency anemia
IDA
The commonest cause of iron deficiency in
children is:
1- Inappropriate diet.
2- Blood loss is uncommon.
Iron deficiency occurs from 6 months of age
onwards when the child’s total body mass
is expanding in the face of an inadequate
iron intake
causes
1-Nutritional iron deficiency usually develops when rapid
growth puts excessive demands on iron stores. This is
seen mainly during:
A-Infancy, when iron stores at birth are inadequate due to
LBW or when the diet is composed exclusively of milk or
cereals with low iron content
B-Adolescence, when a rapid growth spurt often
coincides with a diet of suboptimal iron content (this is
a particular problem in girls, who also lose iron with
menses)
2-Iron deficiency resulting from blood loss.
A-Prenatal iron loss can result from extrusion of
fetal blood either into the maternal circulation
(fetomaternal transfusion) or into the circulation
of a twin (twin-to-twin transfusion).
B-Perinatal bleeding may result from obstetric
complications such as placental abruption or
placenta previa.
C-Postnatal blood loss may be of an obvious
cause (e.g., after surgery or due to trauma) or
may be occult, as occurs in idiopathic pulmonary
hemosiderosis, parasitic infestations, polyps, or
inflammatory bowel disease.
Clinical features.
ID is most commonly seen between 6 and 24 months of
age. The typical patient is on a diet consisting almost
exclusively of milk.
Symptoms. Although mild iron deficiency is
relatively asymptomatic, as it becomes more severe,
the infant manifests
1-irritability
2-anorexia
3-lethargy
4-pica (eating non-food stuffs)
5-apathy
6-easy fatigability.
Signs. On physical examination, the milk-fed infant
is
1-fat
2-pale
3-other findings include tachycardia and a systolic
murmur. If the anemia is very severe, there may
be signs of congestive heart failure .
4-other signs (such as koilonychia or angular cheilitis)
are very rare.
ID causes serial changes in the blood before
anemia develops.
Serum ferritin is reduced and eventually a
microcytic, hypochromic anemia results. Usually
the MCV (mean cell volume) and MCH (mean
cell hemoglobin) fall before the Hb, but the
changes can occur together. The MCHC (mean
cell Hb concentration) is less useful .
stages of iron depletion
Diagnosis
1-CBC: Anemia may vary from very mild to very
severe, depending on the degree and duration
of ID.
Small, pale RBCs are evident on the peripheral
smear; the reduction in MCV, MCH and MCHC
is usually proportional to the severity of the
anemia.
2-The serum iron level is decreased,
whereas the iron-binding capacity
(transferrin level) is increased, and the
percentage of saturation is low (usually
<15%).
The serum ferritin level is decreased
(which is a reflection of low iron stores
in the bone marrow), and the sTR
level is increased.
Differential diagnosis
1.Anemia of chronic disease or ‘anemia of
inflammation’ (modification of iron
regulation by the inflammatory response).
2.Thalassemia traits , these require
quantitation of Hb A2 and F, and not
simply Hb electrophoresis.
3.Sideroblastic anemias .
4-Lead poisoning.
Iron deficiency and neuropsychological effects
ID early in life will affects brain iron content
and distribution, leading to neurotransmitter
& behavioral alterations. IDA is significantly
associated with poorer scores in
developmental testing when compared with
controls, particularly in coordination and
spatial orientation skills.
Therapy
IDA can be managed by administration of iron.
This can be provided by the oral route at a dosage
of 6 mg/kg/day of elemental iron for a period of 2
to 3 months after the Hb level has returned to
normal; this allows replenishment of tissue iron
stores.
Dietary counseling must be simultaneously
provided to caregivers to give the patient
adequate amounts of dietary iron.
Dietary iron occurs in two forms , heme and
nonheme.
Heme iron (in meat, fish and poultry) is well
absorbed and its bioavailability is not affected
by other dietary factors.
Non-heme iron is less well absorbed and its
bioavailability is affected by dietary factors
because of the way it is bound in foods. It is
present in beans, peanut butter, green leafy
vegetables, dried fruit and fortified breakfast
cereals.
Absorption of iron is enhanced by vitamin C and
proteins, but is inhibited by a number of
constituents of food and drink, for example
tannins (in tea and legumes), phytates (in
unrefined cereals), phosphates (in eggs),
oxalates (in spinach) and polyphenols (in
spinach, coffee).
Failure to respond to iron therapy, the
commonest reason is due to failure of
adherence.
Although many preparations may be
prescribed three times a day, better
adherence may be achieved with a single
daily dose or twice daily dosing.
Types of iron
1. Iron salts (e.g. sulphate, fumarate, gluconate
and glycine sulphate).
2. Polysaccharide iron complex. It has major
advantages in pediatric practice . They do not
stain the teeth and it can be mixed with milk or
juice without altering absorption.
In general there are fewer GIT side-effects, and
they are sugar-free. Perhaps most importantly,
the child usually likes them.
Anemia of inflammation
and chronic disease
The anemia of chronic disease is associated with
a variety of disorders, including:
1-Chronic inflammatory disease (e.g., Crohn
disease , juvenile inflammatory arthritis)
2-Chronic infection (e.g. T.B)
3-Malignancy
4-A mild & transient form of anemia of inflammation
may occur following infections, including common
viral infections
Iron is not released from its storage sites in
the macrophages; thus, it is unavailable for
Hb synthesis in developing erythroblasts.
A modest decrease in the survival of RBCs
and a relatively limited erythropoietin
response to the anemia also contribute to
the development of anemia.
Diagnosis
The anemia is mild in degree (i.e. Hb is 7–10
g/dL) often with hypochromic,microcytic indices.
As in IDA, the serum iron level is reduced.
However, in contrast with IDA, the iron-binding
capacity is normal or reduced, and the serum
ferritin( which is acute-phase reactant) level is
increased or normal.
Therapy
The anemia resolves when the underlying
disease process is treated adequately.
Therapy with medicinal iron is unnecessary
unless concomitant iron deficiency is present.
Megaloblastic anemias
MA
Folate deficiency
Etiology
MA is very rare indeed in children but when it does
occur it is most commonly due to folate deficiency. Unlike iron,
folate stores are relatively labile and in constant need of
replenishment.
Folates are required for nucleic acid synthesis and 1-carbon unit
transfer in all cells of the body, particularly growing tissues.
MA occurs after 2–3 mo on a folate-free diet.
Rapid growth, fever, infection, diarrhea or hemolysis all increase
folate requirements and may further deplete the stores to the
level of clinical deficiency.
Folate is absorbed in the upper jejunum by an active transport
mechanism that is impaired in malabsorption states, particularly
celiac syndrome.
Various drugs are associated with deficiency of folate, e.g. phenytoin,
barbiturates, methotrexate, and TMP.
Maternal folate deficiency predisposes to neural tube defects and
possibly to other congenital abnormalities including Down syndrome.
Congenital deficiencies of several enzymes in the folate pathway are
described.
Clinical features and diagnosis
The presentation, like many hematological disorders, is nonspecific.
Folate deficiency will produce macrocytosis (which can be masked by
associated iron deficiency in conditions with malabsorption); more
severe forms will be associated with leucopenia and thrombocytopenia.
Hypersegmented neutrophils on the blood film is an important
clue. Serum and red cell folate levels should be requested to confirm the Dx
Treatment
It is straightforward with oral folic acid in a dose of 1–5 mg/d
& should be continued for several months. Where demand for
folate remains high (e.g. in chronic HA) lifelong supplementation may be
required. There is often a dramatic clinical response within a few days with a
reticulocytosis by the end of a week.
Vitamin B12 deficiency
It is very rare indeed in childhood. The infant usually has an insidious
onset of pallor, lethargy and anorexia, often with neurological symptoms.
With the popularity of vegetarianism, maternal dietary deficiency may
produce profound deficiency in infancy with neurological sequelae and is
currently the commonest cause of infantile B12 deficiency. It may occur
in older children as part of a more generalized GIT disease with
malabsorption.
B12 deficiency has been reported in infants whose mothers have
undergone gastric bypass procedures for obesity, and those whose
mothers are in the early stages of traditional pernicious anemia. B12
deficiency occurs in early infancy due to congenital defects in the
absorption or metabolic pathway.
The diagnosis should be considered in any infant who develops
pancytopenia with MA in the first 3 years of life.
Diagnosis
The blood picture is indistinguishable from folate deficiency – there is often
a pancytopenia with macrocytosis. The serum vitamin B12 level
will be low.
Treatment
The usual dose of vitamin B12 (as hydroxocobalamin) for children is
100 μg, given intramuscularly, three times a week until the hemoglobin
is normal, followed by 100 μg monthly thereafter. Some disorders may be
successfully treated with oral B12 therapy. The neurological defects may
take longer to recover.
Congenital pure RBC aplasia (Diamond-Blackfan syndrome)
a lifelong disorder, usually presents in the first few months of life or at birth
with severe anemia and mild macrocytosis or a normocytic anemia. It is
due to a deficiency of BM red blood cell precursors.
More than a third of patients have short stature. Many pts respond to
corticosteroid treatment, but must receive therapy indefinitely. Pts who do
not respond to steroid treatment are transfusion dependent and are at risk
of the multiple complications of long-term transfusion therapy, especially
iron overload.
These pts have a higher rate of developing leukemia or other hematologic
malignancies than the general population.
Transient
Erythroblastopenia of Childhood(TEC)
a normocytic anemia caused by suppression of RBC synthesis,
usually appears after 6 month of age in an otherwise normal infant.
Viral infections are thought to be the trigger, although the mechanism
leading to RBC aplasia is poorly understood. The onset is gradual, but
anemia may become severe. Recovery usually is spontaneous.
Differentiation from Diamond-Blackfan syndrome, in which erythroid
precursors also are absent or diminished in the BM, may be
challenging. Transfusion of packed RBCs may be necessary if
the anemia becomes symptomatic before recovery.
Thalassemias
Definition. Thalassemias are hereditary hemolytic
anemias characterized by decreased or absent
synthesis of one or more globin subunits of the Hb
molecule.
α-Thalassemia results from reduced synthesis of
α-globin chains.
β-thalassemia results from reduced synthesis of βglobin chains.
An imbalance in globin chain production is a
hazard to the RBC because excess unpaired
globin chains produce insoluble tetramers that
precipitate, causing membrane damage.
This makes RBCs susceptible to destruction
within the reticuloendothelial system of the BM
(resulting in ineffective erythropoiesis) as well
as the RES of the liver and spleen (resulting in
hemolytic anemia).
The types and quantities of different Hb in infancy & adulthood
Type of Hb
Notation
HbA
HbF HbA2
α2β2 α2γ2 α2δ2
Normal % at birth
20
80
1
Normal % in older children
98
1
2
α-Thalassemias
α-Thalassemias are usually the result of gene
deletion.
α-Thalassemia variants are found most often
in populations of African or East Asian
ancestry.
Normally there are four α-globin genes; clinical
manifestations of α-thalassemia variants reflect
the number of genes affected
1-α-thalassemia major: 4 genes deleted
(Hb Bart ) , Hydrops fetalis/death in
utero .
2-Hemoglobin H disease:3 genes deleted,
(Hb H ), baby born with severe anemia,
mild jaundice & splenomegaly
3-α-Thalassemia minor : 2 genes deleted,
Mild anemia .
4-Silent carrier :one gene deleted, No
anemia
β-Thalassemias
The clinical phenotype of β-thalassemia is related
to the degree of globin chain imbalance.
1-Heterozygous β-thalassemia
(β-thalassemia minor).
2-Homozygous β-thalassemia
(β-thalassemia major, Cooley anemia, and
intermedia).
Heterozygous β-thalassemia
(β-thalassemia minor)
Clinical features.
1- Mild anemia (Hb about 10 gm/dl)
2- Normal growth and development.
3- Blood film: Hypochromia, microcytosis, and
anisocytosis.
4- Hb electrophoresis shows elevation of the Hb A2
level and, sometimes, elevation of the Hb F level.
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Therapy: No treatment is necessary.
It is important, however, that
thalassemia minor is distinguished from ID
to prevent inappropriate therapy with
medicinal iron.
Folic acid may be given.
Genetic counseling is also important.
Homozygous β-thalassemia
Homozygous β-thalassemia (β-thalassemia major,
Cooley anemia, and intermedia). Patients who have
this form of anemia are usually of Mediterranean
background.
Defect. Molecular defects range from complete
absence of β-globin synthesis (genotype β0/β0) to
partial reduction in the gene product from the
affected locus (genotype β+/β+).
Clinical features: beginning in the middle of the
first year of life
1- the infant manifests a progressively severe HA
& jaundice .
2- marked HSM.
3- FTT
4- BM hyperplasia produces characteristic
features such as tower skull, frontal bossing,
maxillary hypertrophy with prominent
cheekbones, and overbite.
5- Hemochromatosis: Even in the untransfused
state, iron overload develops in thalassemic pt
because of hyperabsorption of dietary iron.
The iron load becomes even greater with chronic
transfusion therapy. When the BM storage
capacity for iron is exceeded, iron accumulates
in parenchymal organs such as the liver, heart,
pancreas, gonads, and skin, producing the
complications of hemochromatosis (“bronzed
diabetes”).
Many patients succumb to congestive HF ,
hypoparathyroidism, hypogonadism , DM , liver
cirrhosis and short stature.
Investigations:
1-CBC : hypochromic microcytic anemia, with
nucleated RBC and retics count commonly less
than 8% which is inappropraitely low to the degree
of anemia due to ineffective rythropoiesis).
2-Elevated unconjucated bilirubin.
3-On Hb electrophoresis, Hb A is either markedly
decreased or totally absent. Of the total Hb
concentration, 30% to 90% is Hb F.
4-BM hyperplasia is seen in bone XR.
5-Elevated S.ferretin & transferrin saturation.
Skull X-ray showing ‘hair on end’ appearance caused by marrow
hyperplasia and expansion
Treatment:
1- The mainstay of treatment is transfusion with packed
RBCs using irradiated CMV –ve blood, a post
transfusion Hb level of 9.5-10 gm/dl is the goal.
2- In an effort to prevent hemochromatosis, pts who
receive chronic transfusion regimens are treated with
chelating agents (e.g., deferoxamine, deferiprone) that
promote iron removal from the body through excretion in
the urine & stool.
Deferoxamine is given subcutaneously over 10-12 hrs,5-6
days a week.
Side effects of deferoxamine includes:
a-ototoxisity.
b-retinal changes.
c-bone dysplasia with truncal shortening.
d-Yersinia bacteria over growth.
3- Splenectomy is usually considered when
transfusion requirements exceed 250
mL/kg/year.
4- bone marrow transplantation can cure the
patients .
5- Genetic counseling .
HEMOLYTIC ANEMIAS
HA
Hemolysis : an increased rate of RBC destruction with a
shortening of the normal life span of the cell from the
normal 120 days to as little as a few days in severe
hemolysis. The marrow can increase erythrocyte
production 6-8 fold so mild degrees of hemolysis are not
associated with anemia.
Severe hemolysis can lead to a rapid and profound fall in
Hb, and be life threatening. It is suspected when
polychromatic cells are seen on the blood film
(reticulocytes).
It is usually associated with raised blood unconjugated
bilirubin and splenomegaly .
Hemolysis can be caused by inherited or acquired
disorders.
Diagnosis of the cause of the hemolysis is made
according to the family history; clinical features
and red cell morphology that together will
indicate what further laboratory tests are
required.
Marrow examination is generally unnecessary.
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The child with hemolysis may be pale with fluctuating
jaundice (usually mild) and splenomegaly.
Pigment gallstones may complicate the disorder ,HA
should always be excluded in a child with stones.
Aplastic crises may occur, usually precipitated by
parvovirus infection which leads to reticulocytopenia
and anemia. Parvovirus infection typically produces
severe anemia sometimes requiring transfusion, and
a modest thrombocytopenia and leucopenia.
Hemolytic anemia
The major categories of HA are:
1-Immunemediated.
2-Membrane defect (Spherocytosis).
3-Enzyme defect(G6PD def).
4-Hb defect (SCA,Thalassemia).
Membrane defects
Hereditary spherocytosis (HS)
HS
It is caused by a defect in the skeleton of the
RBC membrane that generally affects the
spectrin component.
The characteristic finding is increased
numbers of spherocytes in the peripheral
blood. It is inherited as A.D in 75% of cases,
other cases inheritant as A.R or new
mutation.
Pathology
In AD type the defect may be in either beta
spectrin,ankyrin or protein 3. In AR form the
defect is in either -protein or protein 4-2.
This defect affect the RBC skeleton leading to
budding of RBC memb, This bud is removed
rapidly by the RES leading to loss of RBC
surface area.The stretching ability of the RBC is
very limited which lead to RBC rupture.
The spherocyte have no easy transit through the
splenic cord because of its shape this will affect
glucose metabolism and decrease pH of RBC.
A, polychromatic cell; B, microspherocyte
Clinical pictures
1-May be asymptomatic with mild anemia & discovered
accidentally.
2-The severe form may be started at early infancy with
neonatal jaundice, severe anemia , splenomegaly &
chronic blood transfusion.
3-Clinical pictures of complication, which are:
A-Bone marrow aplasia after Parvo virus B19 infection.
This v. infect erythroid cells in the BM & with arrest in
development. The aplasia last for 10-14 days during
which time the Hb drops by 50% with reticulocytopenia.
B-Hyper hemolysis after some viral infection lead to
increasing anemia, reticulocytosis &jaundice.
C-Delayed growth and sexual developments.
D-Pigmented gallstones.
Laboratory diagnosis
1-CBC:A-anemia.
B-high MCHC>36.
C-high retic. count.
D-normal MCH & MCV.
E-spherocytes in peripheral blood.
2-Incubated osmotic fragility test is elevated.
3-High indirect bilirubin.
4-Decrease habtoglobin.
5-Membrane protein analysis for difficult cases
Management
1-In mild anemia with normal growth and development,we
only observe the child and limit the intervention to folic
acid tablet 1 mg/day.
2-Splenectomy for any child with chronic anemia or growth
failure but we should defer it till the age of 5 yr to
minimize the risk of sepsis & we should vaccinate the
child by pneumococcal , H. influenza & menengiococcal
vaccines at least 2 weeks before splenectomy & give the
child prophylactic penicillin after splenectomy until at
least 18 yr of age.
In some reports,partial splenectomy appears to improve
the anemia & maintain splenic function.
3-Elective cholecystectomy for symptomatic gallstones.
Glucose-6-phosphate
dehydrogenase(G6PD)
deficiency
G6PD deficiency is the most common RBC metabolic disorder.
It is usually transmitted in an X-linked recessive fashion.
Defects. The two prototypic forms are:
The A- variant is found mainly in the black population
and is associated with an isoenzyme that deteriorates
rapidly (it has a half-life of 13 days).
The Mediterranean variant is found mainly in
individuals of Greek and Italian descent and is
associated with almost complete absence of enzyme
activity, even in young cells, due to extreme instability
(it has a half-life of several hours).
Pathogenesis
G6PD-deficient cells do not generate an amount of reduced
glutathione that is sufficient to protect the RBCs from
oxidant agents.
Exposed sulfhydryl groups of Hb are oxidized, predisposing
the molecule to denaturation.
The heme and globin moieties dissociate, with the globin
precipitating as Heinz bodies.
The damaged RBCs are then removed by the RES; severely
damaged cells may lyse intravascularly.
HA results from oxidative damage to the
RBCs as consequence of the loss of the
protective effect of the enzyme G6PD.
The prevalence of G6PD def. is related to
the prevalence of malaria as in Africa, it
also high in mediterranean area.The
incidence of P falceparum parasite is
lower in G6PD def. patients.
The half life of the enz in normal RBC is 60 days,the mature
RBC cannot synthesize the enz. The younger RBCs are
relatively more resistant to hemolysis .
The deficient RBC hemolysed when exposed to exogenous
factors.The particles of the denaturated Hb,Heinz
body,attach to the cell membrane causing irreversible
damage and lysis, most of lysis occur intravascularly causing
hemoglobinemia & hemoglobinuria.
There may be an extravascular hemolysis which explain the
splenomegaly in some cases.
Favism is the classical cause of acute hemolysis in G6PD def.
Fava bean contain the beta glycosides vicine & convicine
These substances may undergo auto-oxidation as part of their
metabolism, producing free O2 radicals.
Acute hemolysis that occurs upon exposure to Fava is
characterized by:
1-unpredictable(only 25%of adult at risk develop
hemolysis).
2-Influence of dose and body weight.
3-Maturity of the bean.
4-Quality of bean(raw beans more than cooked, frozen or
canned beans)
5-The activity of beta glucosidases in the bean & intestinal
mucosa.
Drug induced hemolysis
Many drugs and chemicals have been associated
with hemolysis in G6PD def patient,These
substances have the ability to stimulate the
pentose phosphate PW in RBC which can lead to
oxidation of NADPH .
Infection-caused hemolysis
During the process of phagocytosis of bacteria
there is a release of peroxides by the
phagocytosing granules, these peroxides lead to
release of O radicals.
Clinical presentation
There are three primary clinical
presentation:
1-Neonatal jaundice.
2-Acute hemolysis beyond the neonatal
period.
3-Chronic hemolysis (congenital nonspherocytic HA).
1-Neonatal jaundice:
Acute hemolysis is characterized by onset of
jaundice on the first few days of life that is out of
the proportion to the degree of anemia. All infant
with G6PD def develop NJ.
NJ in G6PD def neonate may be an
exaggerated physiological j or may be due to
acute hemolysis caused by inciting agent like
inf., drugs, naphthalene ball used in stored cloth
diapers in developing country.
2-Acute hemolysis:
Most pt with G6PD def. are asymptomatic until
exposed to inciting agent at which time they may
develop hemolysis.The onset of hemolysis is
usually within 24-48 hr of exposure. The initial
manifestation may include abdominal
pain,vomiting or diarrhea,tea colored urine
(hemoglobinuria),Jaundice, pallor with symptoms
of anemia.
Examination usually reveals: anemia , jaundice
splenomegaly and hepatomegaly & in severe
case symptom of heart failure.
Lab.finding in acute hemolysis include:
1-Normochromic normocytic anemia with anisopoikilocytosis,
with few spherocyte .
2-Reticulocytosis.
3-Presence of bite cells (RBC bitten by macrophages).
4-Presence of hemigoast cells(RBC with uneven Hb
distribution).
5-By using supravital stain we find inclusion bodies called
Heinz body(denatured Hb).
6-Low serum haptoglobin.
7-High uncong. bilirubin.
8-Hemoglobinuria .
9- hemoglobinemia.
Diagnosis of G6PD def
1-Antenatal diagnosis can be made by performing
G6PD assay on amniotic fl cells or from
chorionic villi biopsy and DNA assay.
2-Screening test:semiquantitative test,this test
should not be done during acute hemolysis
because it lead to normal value.The usual cut of
deficiency value is <30% of normal activity.
3-Quantitative assay: done several weeks after
acute hemolysis when reticulocyte return to
normal.
4-G6PD electrophoresis.
Differential diagnosis:
1-AIHA.
2-Malaria induced hemolysis.
3-Hepatitis
Management of acute severe hemolysis
1-Removal of the inciting agent.
2-Brisk hydration to ensure adequate urine output.
3-blood transfusion.
4-Folic acid tablet 1mg/d for one month.
3-Chronic hemolysis
Small minority of pt develop chronic H.Clinically all
pts are male,presented with:
1-Neonatal j with anemia.
2-Jaundice and anemia.
3-splenomegaly.
4-Gallstone.
5-Acute hemolysis after exposure to oxidative agent.
Lab. Finding:
1-CBC:anemia,reticulocytosis & polychromasia.
2-Low haptoglobin.
3-Hyberbilirubinemia.
Management
1-Folic acid administration.
2-Blood transfusion if indicated.
Drugs induce hemolysis in G6PD:
ANALGESICS/ANTIPYRETICS acetophenetidin ,
amidopyrine ,aspirin ,phenacetin, probenicid .
ANTIMALARIALS chloroquine, hydroxychloroquine
mepacrine, pamaquine, pentaquine, primaquine, quinine,
quinocide
SULFONAMIDES/SULFONES dapsone, sulfacetamide,
sulfamethoxypyrimidine, sulfanilamide ,sulfapyridine
sulfasalazine ,sulfisoxazole .
ANTIBACTERIAL chloramphenicol, cotrimoxazole,
furazolidone, nalidixic acid, nitrofurantoin nitrofurazone ,
para-aminosalicylic acid.
MISCELLANEOUS alpha-methyldopa, ascorbic acid
dimercaprol (BAL), hydralazine , methylene blue ,nalidixic
acid ,naphthalene, vitamin K (water soluble)
Hb S disorders
(Sickle cell disorders)
Defect and pathogenesis
The molecular defect is the result of an
abnormal autosomal gene that substitutes
valine for glutamic acid in the 6th position of
the β-globin chain.
Under conditions of hypoxia, the Hb aggregates
into insoluble long polymers that align
themselves into rigid paracrystalline gels ,
which distort the RBC into a sickle shape.
The clinical consequences of the
solubility anomaly are:
1-Shortened red blood cell survival (hemolytic
anemia)
2-Microvascular obstruction, which leads to
tissue ischemia and infarction
There are two types of Hb S disease:
1- Heterozygous state (sickle cell trait )
2- Homozygous state (sickle cell anemia)
Heterozygous state (sickle cell trait)
Both Hb A and Hb S exist in individuals who
have sickle cell trait; there is more Hb A than
Hb S.
Clinical features:
Sickle cell trait is usually asymptomatic,
unless the affected individual is subjected
to hypoxemic stress. Otherwise,
abnormalities may be limited to:
1- failure to concentrate urine.
2- painless hematuria, or both.
Diagnosis:
Sickle cell trait may be diagnosed by Hb
electrophoresis or solubility tests (e.g slide test).
It is important to detect the trait for purposes of
genetic counseling.
Therapy:
No specific treatment is required; however,
precautions to avoid hypoxemia associated with
severe pneumonia, unpressurized flying, exercise
at high altitudes, and G/A are in order. Tourniquet
surgery and deep hypothermia should be avoided
Homozygous state
(sickle cell anemia)
Clinical pictures:
1-In the asymptomatic period, the high
levels of Hb F during fetal life and the first
few months of postnatal life protect the
patient.
2- Dactylitis :
The earliest clinical manifestation may occur
at 4 to 6 ms of age, when symmetric, painful
swelling of the dorsal surfaces of the hands
and feet develops. This is caused by
avascular necrosis of the bone marrow of the
metacarpal and metatarsal bones.
During this same period, progressive anemia
with jaundice and splenomegaly begins to
develop.
3-Splenic sequestration crises: The spleen may
suddenly become engorged with RBCs, trapping a
significant portion of the blood volume.
The child may presented with sudden severe pallor ,
severe abdominal pain and huge splenomegaly
If not corrected rapidly, this can lead to hypovolemic
shock and death.
4- Overwhelming infections:
Pts are very susceptible to overwhelming
infection, particularly with encapsulated
bacteria such as pneumococci and
Haemophilus influenzae; Salmonella
septicemia and osteomyelitis are also
seen with increased frequency in pts who
have SCA.
5-Aplastic crises can occur at any age
when there is suppression of
erythropoiesis in response to a viral
infection such as parvovirus B19 .
6-Vaso-occlusive episodes can involve any
tissue. Depending on the involved organ.
A vaso-occlusive episode can produce abdominal
pain, bone pain, cerebrovascular accident
(CVA), pulmonary infarction (acute chest
syndrome) , hepatopathy, or hematuria. These
episodes are often precipitated by infection,
dehydration, chilling, vascular stasis, or acidosis.
Repeated vaso-occlusive episodes in the
spleen lead to infarction and fibrosis of this
organ; it gradually regresses in size and is
usually no longer palpable after the age of
5 years.
6-Late manifestations.
By the time a pt reaches his late teens or early
20s, he is suffering the long-term consequences
of chronic anemia, and tissue infarction.
Many succumb to progressive myocardial damage
with congestive heart failure.
Other long-term complications include gallstones,
leg ulcers, renal damage, and aseptic necrosis
of the long bones.
Treatment of SCA
1-Infections. Because these patients suffer from
functional asplenia, the same precautions to
protect them from overwhelming Gram-positive
sepsis must be taken as for the patient whose
spleen has been surgically removed.
However, after the age of 5, there is little evidence
to suggest that routine penicillin prophylaxis is
required.
2-Vaso-occlusive episodes.
Prevention by avoidance of dehydration, hypoxia,
chilling, and acidosis.
Treatment is as follows:
-Analgesics should be given for pain.
-When a vital organ (the brain, liver, or lung)
is threatened, transfusion with packed
RBCs may be necessary.
-After a documented CVA, the pt remains at high
risk for recurrent CVAs for an indefinite period of
time; such pts should be maintained on a
chronic transfusion program designed to keep
the Hb S level at <30%.
As is the case with chronic transfusion programs
for pts who have thalassemias, iron overload
may eventually necessitate chelation therapy
3-Use of agents that elevate Hb F levels.
Because Hb F levels correlate inversely with
disease severity, efforts have been made to
identify medications that might increase Hb F
levels in sickle cell anemia pts.
Hydroxyurea has become the drug most
commonly used for this purpose; early trials
have indicated improvement in both laboratory
and clinical parameters for children treated with
this agent.
4- Severe aplastic crises should be treated by
transfusion with packed RBCs .
5- HSC transplantation from healthy, HLA-matched
sibling donors has proved to be potentially
curative; however, this approach is limited by the
paucity of HLA-matched siblings and the toxicity
of the conditioning regimens.
Antibody-mediated
hemolytic anemias
General considerations
1-Autoimmune hemolytic anemias (AIHA):
are the result of antibodies generated by
an individual's immune system against his or her
own RBCs.
2- Isoimmune hemolytic anemias:
result from antibodies produced by one individual
against the RBCs of another individual of the same
species. It can be seen in hemolytic disease of the
newborn or hemolytic transfusion reactions (e.g.,
the transfusion of type A blood into an individual
who has type B blood).
Autoimmune hemolytic anemias
Etiology :
AIHA may be idiopathic or the result of
infectious agents, drugs, lymphoid
neoplasms, or disorders of immune
regulation (e.g., SLE, agammaglobulinemia)
Typical antibodies involved
1-Antibodies of the IgG class, for the most part, are
warm reactive (i.e., they have maximal activity at
37°C). They are detected using the direct
antiglobulin (Coombs) test.
-These are incomplete antibodies in that they do
not agglutinate RBCs, although they coat the
surface.
-Hemolysis occurs extravascularly .
-IgG antibodies are associated clinically with
autoimmune diseases, lymphomas, and viral
infections. Occasionally, no underlying cause is
demonstrable.
2-Antibodies of the IgM class are usually cold
reactive (i.e., most have maximal activity at low
temperatures).
-These are complete antibodies in that they
agglutinate RBCs and activate the complement
sequence through C9, causing lysis of RBCs.
-Hemolysis occurs intravascularly .
-IgM antibodies are associated clinically with
mycoplasmal pneumonia, Epstein-Barr virus,
and transfusion reactions.
3-Donath-Landsteiner antibody:
-It is of the IgG type, but it is exceptional in that it
reacts best in the cold and can activate
complement, causing hemolysis to occur
intravascularly .
-Its clinical associations include syphilis and viral
infections.
It may also be idiopathic.
Therapy:
depends on the cause, clinical condition of the pt,
& expected duration of the illness. Because most
cases of childhood AIHA are idiopathic or
postinfectious and self-limited, supportive care
and judicious use of transfusions and
corticosteroids are the therapies most commonly
used.
Treatment modalities include:
1. Supportive care with bed rest
and oxygen
2. Transfusion with packed RBCs
3. Corticosteroids
4. Splenectomy
5. Immunosuppressive agents