2. ANEMIA
INTRODUCTION
Anemia is a common problem in children. About 20% of children in the
U.S. will be diagnosed with anemia at some point.
Red blood cells carry oxygen throughout the body using a protein called
hemoglobin. If there aren’t enough of these cells or this protein, anemia
results.
Anemia is a sign, it is important to investigate the cause of anemia to
ensure that it is not due to a serious underlying ailment and to define the
correct management approach. 2/13/2023 2
3. DEFINITION
Anemia is present when the hemoglobin level in the blood is two
standard deviations below the mean for the particular age and sex.
The physiologic definition of anemia is a condition in which tissue
hypoxia occurs due to inadequate oxygen carrying capacity of blood.
According to the National Family Health Survey {NFHS-4) data, the
incidence of anemia in urban children is 55.9%, rural is 59.4% and
overall is 58.4%.
2/13/2023 3
6. CLINICAL FEATURES
Tiredness, lassitude, easy fatigability and generalized
muscular weakness are most frequent and the earliest
symptoms of anemia.
This presents as poor feeding, irritability and inadequate
school performance; pallor.
2/13/2023 6
7. CLINICAL FEATURES
Pallor of nail beds, oral mucous membranes and
conjunctivae.
Dyspnea on exertion, tachycardia and palpitation
Hemic murmurs. They are heard in the pulmonary
area.
2/13/2023 7
9. CLINICAL FEATURES
Systolic bruits (obstructed flow), postural hypotension and congestive heart
failure may be seen in patients with moderate to severe anemia.
Nervous system symptoms: dizziness, headache, humming in ears, fainting, tinnitus,
lack of concentration and drowsiness; with severe anemia, clouding of consciousness.
Severe anemia is characterized by a high output state with elevated pulse pressure
and a 'collapsing' character.
2/13/2023 9
10. CLINICAL FEATURES
Electrocardiographic changes may be found in approximately 30% of patients with
hemoglobin of less than 6 g/dL.
Findings on ECG are normal QR waves, depression of the ST segments, and
flattening or inversion of T waves.
2/13/2023 10
11. APPROACH TO DIAGNOSIS
1. History may give clues for the etiology of anemia.
Obstetric history of maternal infections, anemia or collagen vascular diseases, or
presence of prematurity, blood loss, jaundice (secondary to ABO or Rh
incompatibility, G6PD deficiency and sepsis), hemangioma or cephalohematoma.
History is taken regarding the diet, type and quality of milk, time of weaning and
intake of vitamins and hematinics.
Nutritional iron deficiency anemia often occurs between 6 months and 2 years due
to inadequate weaning, chronic diarrhea or cow milk allergy.
2/13/2023 11
12. APPROACH TO DIAGNOSIS
Adolescent growth spurt, menstruating and pregnant teens are at risk for iron
deficiency.
A vegetarian diet and use of goat milk may result in megaloblastic anemia.
History of pica, drug intake, chronic diarrhea, acute and prolonged infections, liver
and renal disease, transfusions and age of onset of symptoms should be taken.
Thalassemia major usually presents at 4-6 months of age, and 70% present with
symptoms by one-year.
2/13/2023 12
13. APPROACH TO DIAGNOSIS
A family history of anemia, gallstones and requirement for blood transfusions may
suggest the diagnosis of chronic hemolytic anemia, including hereditary spherocytosis
or G6PD deficiency.
2. Examination
Examination is done for clues to the cause of anemia, e.g. radial limb anomalies
(bone marrow failure), splenomegaly (hemolytic anemia, infection, storage diseases),
and lymphadenopathy and hepatosplenomegaly (malignancies, malaria, tuberculosis).
Petechia, purpura, icterus and bossing also help to diagnose the cause.
2/13/2023 13
15. APPROACH TO DIAGNOSIS
Laboratory investigations
The complete hemogram will reveal, if there is isolated anemia, or if other cells are
affected.
The red cell indices will demonstrate the type of anemia; while the mean corpuscular
volume (MCV) denotes the size of the red cells, the mean corpuscular hemoglobin
(MCH) and mean corpuscular hemoglobin content (MCHC) provide information
on red cell hemoglobinization.
2/13/2023 15
17. LABORATORY INVESTIGATIONS
Using the MCV, anemia can be classified into microcytic/normocytic/macrocytic
anemia.
The red cell distribution width (RDW) gives the size difference in the red blood
cells, low RDW means all the red blood cells are small and uniform in size, while a
large RDW shows that the cells vary in size greatly.
Examination of the peripheral smear will reveal the red cell morphology. Presence of
schistocytes, polychromasia, specific red cell morphology or parasites may help in
making the diagnosis.
2/13/2023 17
21. LABORATORY INVESTIGATIONS
The reticulocyte count helps to determine if anemia is caused by red cell destruction
or decreased production.
In cases of anemia with increased reticulocyte count, a Coombs test will help to
identify, if this is due to immune or hereditary hemolytic anemia.
When nutritional anemias are suspected, iron status, vitamin B12 and folic acid
levels determined.
2/13/2023 21
28. INTRODUCTION
Iron-deficiency anemia is anemia caused by a lack of iron.
Iron deficiency anemia occurs when there is a decrease in total iron body content,
severe enough to diminish erythropoiesis and cause anemia.
It is the most common cause of anemia worldwide.
2/13/2023 28
37. CLINICAL EVALUATION
Dietary history: intake of milk, weaning foods and supplements.
Pica increases the risk of infestations and lead poisoning.
Common features of anemia are present.
Behavioral symptoms: irritability and anorexia, precede weakness, fatigue, leg
cramps, breathlessness and tachycardia.
Congestive heart failure and splenomegaly may occur with severe, persistent,
untreated iron deficiency.
2/13/2023 37
39. TREATMENT
The cause of anemia should be identified and corrected.
Hookworm infestation is the commonest cause of occult gastrointestinal blood loss
in rural India at all ages.
Close follow-up is required to assess for adequate response and correction of anemia,
this will help to identify iron therapy failure.
2/13/2023 39
41. ORAL IRON PREPARATIONS
Should be taken on an empty stomach or in
between meals for best absorption.
The most cost- effective oral preparation is
ferrous sulfate.
2/13/2023 41
42. TREATMENT
The dose for treatment of anemia is 3-6 mg/kg/day elemental iron.
The reticulocyte count increases within 72-96 hours after initiating therapy.
After correction of anemia, oral iron should be continued for 4-6 months to replenish
iron stores.
2/13/2023 42
43. TREATMENT
As iron deficiency anemia is readily corrected with medication, blood transfusions
should be avoided in young, stable patients.
Red cell transfusions are needed in emergency situations, as in patients where the
rate of blood loss exceeds the expected rise of hemoglobin, for urgent surgery,
hemorrhage or severe anemia with congestive cardiac failure.
In very severe anemia with congestive cardiac failure, transfusions must be given very
slowly (2-3 ml/kg) with monitoring and diuretic therapy if necessary.
2/13/2023 43
44. MEGALOBLASTIC ANEMIA
Megaloblastic anemia is a distinct type of anemia characterized
by macrocytic red blood cells and erythroid precursors, which
show nuclear dysmaturity.
It impaired DNA synthesis that results in enlarged red blood
cells.
The incidence varies with dietary practices and socioeconomic
patterns.
A study has estimated the incidence of folate deficiency as 6.8%,
vitamin B12 as 32% and combined deficiency as 20% in north
Indian children. 2/13/2023 44
51. CLINICAL MANIFESTATIONS
Anemia, anorexia, irritability and easy fatigability.
Patients should be examined for signs of thrombocytopenia
and neutropenia.
Features characteristically found in megaloblastic anemia
include glossitis, stomatitis and hyperpigmentation of the
skin on knuckles and terminal phalanges, enlargement of
liver and spleen (30-40% cases).
2/13/2023 51
52. CLINICAL MANIFESTATIONS
Petechiae and hemorrhagic manifestations have been
reported in 25% cases.
Pancytopenia.
A neurologic examination is mandatory, it may reveal loss
of position and vibratory sensation, memory loss, confusion
and neuropsychiatric symptoms can occur.
2/13/2023 52
53. LABORATORY EVALUATION
The reticulocyte count should be performed; if available, serum B 12 and folate
levels are assayed.
The Schilling test, (to determine absorption of vitamin B-12) which requires radioactive labeled
B12, is used to identify pernicious anemia and for evaluation of deficiency states.
2/13/2023 53
54. LABORATORY EVALUATION
Bone marrow evaluation should be performed in any child with more than one
abnormal hematological cell line.
Serum chemistry may reveal elevated lactic dehydrogenase (LDH) and bilirubin.
2/13/2023 54
56. DIFFERENTIAL DIAGNOSIS
Other causes of macrocytosis should be considered in the differential diagnosis of
megaloblastic anemia.
These causes include aplastic anemia and marrow failure syndromes, congenital
dyserythropoietic anemia, chronic liver disease, hypothyroidism, neoplastic and HIV
infections.
2/13/2023 56
57. TREATMENT
Treatment depends on the underlying cause.
If the cause is not identified, therapeutic doses of folate (1-5 mg/ day) and vitamin
B12 (1000 µg) are administered.
Only folate therapy may correct the anemia, but will not correct cobalamin
deficiency-associated neurological disorder and result in the progression of
neuropsychiatric complications.
Folate deficiency due to dietary insufficiency or increased demands is best treated
with folate supplements.
2/13/2023 57
58. TREATMENT
Folate deficiency due to use of anti-folate medications (proguanil, pyrimethamine and
trimethoprim) is managed by reducing or eliminating the implicating agent and
supplementation with folic acid.
Folate is available as 5 mg tablet and overdose is not associated with any adverse
effects; a dose of 1-5 mg/day is recommended for 3-4 weeks.
2/13/2023 58
59. TREATMENT
Parenteral vitamin B12 at a dose of 1 mg (1000 µg) is given intramuscularly; lower
doses (250 µg) can be used in infants.
A decrease in MCV, reticulocytosis and higher platelet and neutrophil counts is
observed within a few days of therapy.
In patients with pernicious anemia and malabsorptive states, vitamin B12 (1000 µg)
should be given IM daily for 2 weeks, then weekly until the hematocrit value Is
normal and then monthly for life.
2/13/2023 59
60. TREATMENT
Patients with neurological complications should receive 1000 µg IM every day for 2
weeks, then every 2 weeks for 6 months and monthly for life.
Oral supplements can be administered; however, absorption is variable and may be
insufficient in some patients.
In dietary insufficiency, no standard duration of therapy has been defined. Dietary
counseling is advised, along with vitamin B12 supplements (oral daily or parenteral
dose every 3-12 months).
2/13/2023 60
62. HEMOLYTIC ANEMIA
The term 'hemolytic anemia' is limited to conditions in which rate of red cell
destruction is accelerated and ability of the bone marrow to respond to the anemia is
unimpaired.
Under maximal stimulation, the normal marrow is capable of increasing its production
about 6-8 times its basal level.
The reticulocyte count is useful in determining the rate of red cell destruction.
The normal reticulocyte count value in the newborn is 3.2+1.4% and in children
1.2+0.7%.
2/13/2023 62
65. CLINICAL FEATURES
In rapidly occurring hemolysis, the symptoms are more
numerous and pronounced.
Evidence of anemia: weakness, pallor, fatigue may be seen.
jaundice is a prominent finding and red urine occurs in
intravascular hemolysis.
2/13/2023 65
66. CLINICAL FEATURES
Splenomegaly is seen in auto immune and many congenital forms of hemolytic
anemia.
The presence of gallstones and icterus (hereditary spherocytosis), hemolytic /
thalassemic facies (thalassemia major, intermedia), leg ulcers (sickle cell disease) can
help lead investigations, confirmatory tests are still required.
2/13/2023 66
67. LABORATORY MANIFESTATIONS
The Coombs test is the most important initially test to perform to define the etiology of
hemolysis.
A direct antiglobin (direct Coombs) test is positive in most cases of immune
hemolytic anemia.
The level of indirect bilirubin provides evidence for hemolysis, it is relatively
insensitive and is elevated only if the liver function is impaired or when hemolysis is
extensive.
2/13/2023 67
68. MANAGEMENT
In an acute attack of hemolysis, it is important to maintain fluid balance and renal
output.
Shock is managed by standard measures.
Blood transfusions.
Even with careful blood matching, destruction of transfused blood with increased
burden on excretory organs and risk of thromboses may occur.
2/13/2023 68
69. MANAGEMENT
Acute autoimmune hemolytic anemia is treated with steroids (prednisone 1-2
mg/kg/day), gradually tapered over several months, once the patient shows resolution of
hemolysis.
In chronic hemolysis, the etiology needs to be investigated and treated accordingly.
2/13/2023 69
70. THALASSEMIA
Thalassemia is a Greek term derived from thalassa, which means "the sea"
(Mediterranean Sea) and emia, which means "related to blood".
It occurs due to globin gene defects, one of the commonest monogenic diseases.
Molecular biology and genetics of thalassemia syndromes have revealed more than
200 mutations, across populations from Southeast Asia to Africa.
2/13/2023 70
71. THALASSEMIA
Carrier rates for thalassemia reported in North Indians, varies in different ethnic
groups from 3-17%.
The major hemoglobin in children after 1 year of age, HbA constitutes
approximately 90%, and a minor component, HbA2 accounts for 23%.
The main hemoglobin in fetal life is HbF of which only traces remain after 1 year of
life.
2/13/2023 71
72. PATHOPHYSIOLOGY
Thalassemia are inherited disorders of hemoglobin synthesis that result from
alteration in the rate of globin chain production.
A decrease in the rate of production of a globin (alpha, beta, gamma, delta) impedes
hemoglobin synthesis and creates an imbalance with normally produced globin chains.
2/13/2023 72
77. BETA THALASSEMIA
2/13/2023 77
- Deficiency of beta globin leads to free alpha
globin.
- Cause hemolysis in bone marrow and spleen.
- Hemolysis causes Hb to enter in blood,
heme= iron + bilirubin
(hemochromatosis+ Jaundice)
79. PRESENTATION
hypochromic, microcytic anemia that does not respond to iron supplementation.
Thalassemia minor are usually asymptomatic.
Children with thalassemia major usually demonstrate no symptoms until about
months of age
2/13/2023 79
82. SPECTRUM OF B THALASSEMIA
Thalassemia major: The condition is characterized by transfusion dependent anemia,
splenomegaly, bony deformities, growth retardation and hemolytic facies in untreated
or inadequately treated individuals.
Blood smear shows hypochromia, microcytosis, fragmented and nucleated red cells,
polychromasia and occasionally immature leukocytes.
Organomegaly is reduced in well-transfused patients
2/13/2023 82
85. PREVENTION AND MANAGEMENT
Genetic counseling: is needed for the couple and their family to prevent the birth of
other children with thalassemia major.
Prenatal testing is available to ensure the second child of the afflicted family does
not have thalassemia major.
2/13/2023 85
87. MANAGEMENT
Blood transfusion should be initiated at an early
age when the child is asymptomatic and attempts
should be made to keep pretransfusion hemoglobin
level at 9-10 g/dL (to promote growth and prevent
deformities).
A normal diet is recommended, with the following
supplements: Folic acid, small doses of ascorbic
acid (vitamin C), and alpha-tocopherol (vitamin E).
2/13/2023 87
88. MANAGEMENT
Blood Transfusions and Infections
After multiple transfusions, patients often develop
transfusion reactions or alloimmunization to red cell
antigens. These complications can be minimized by using
leukocyte filters during transfusion or having blood banks
prepare leuko-poor packed red cells.
Administration of acetaminophen and
diphenhydramine hydrochloride before transfusion(s)
minimizes febrile or allergic reactions.
2/13/2023 88
90. BLOOD TRANSFUSIONS AND INFECTIONS
The major complications are those related to transmission of blood-borne viral
infections.
Hepatitis B vaccination and regular assessment of hepatitis C and HIV status are
part of routine care.
Folate supplements are required; ferritin levels are used to monitor iron overload.
2/13/2023 90
91. IRON OVERLOAD
Iron overload is a major cause of morbidity.
The excessive load of iron is due to increased gastrointestinal iron absorption as well
as repeated transfusions.
Patients show signs of endocrinopathy affecting pancreas, thyroid and parathyroid
glands, decreased growth and lack of sexual maturation.
2/13/2023 91
92. CHELATION THERAPY
The introduction of chelating agents capable of removing excess iron from the body
has dramatically increased life expectancy.
The cost, however, has resulted in poor compliance and inadequate dosing of iron
chelators in many patients.
Combination therapy may be needed in children not adequately controlled by
appropriate use on a single iron chelator.
2/13/2023 92
93. CHELATION THERAPY
Deferoxamine (DFO) is administered by subcutaneous infusion pump (40-60 mg/kg/
day over 8-12 hours for 5-6 days/week).
Higher doses of DFO may be administered IV when serious iron overload such as
cardiac failure occurs.
Eye examinations, hearing tests and renal function tests are required to monitor the
effects of DFO therapy.
2/13/2023 93
94. CHELATION THERAPY
Deferasirox is an oral chelating agent, which binds iron with high affinity and is
excreted in bile and via the feces.
The dose is 30 mg/kg dissolved in water and taken daily.
Deferiprone is an oral chelating agent, which is less effective than DFO in preventing
organ damage.
It is administered at a dose of 75 mg/ day, but should be given under supervision for side
effects including arthritis, neutropenia and agranulocytosis.
2/13/2023 94
95. SPLENECTOMY
The spleen acts as a store for nontoxic iron, protecting the body from extra iron thus
early removal of the spleen may be harmful.
Splenectomy is justified only in hypersplenism, leading to excessive destruction of
erythrocytes and thus increasing the need for frequent blood transfusions, resulting in
further iron accumulation.
Patients who require more than 200-250 mL/ kg of packed red blood cells per year to
maintain hemoglobin may benefit from this procedure.
2/13/2023 95
96. SPLENECTOMY
Pre-splenectomy immunizations and prophylactic antibiotics have significantly
decreased infections in splenectomized children.
The procedure is delayed until the child is aged 5 years old. This is rarely required in
children receiving adequate transfusion therapy.
2/13/2023 96
98. ALPHA THALASSEMIA
Alpha-thalassemia: is a form
of thalassemia involving the
genes HBA1 and HBA2.
Alpha-thalassemias are most
commonly inherited in
a Mendelian recessive manner.
They are also associated with
deletions of chromosome 16p.
2/13/2023 98
105. ERYTHROBLASTOSIS FETALIS/ HYDROPS FETALIS
2/13/2023 105
- life-threatening condition in which a fetus or
newborn has an abnormal buildup of fluids in the
tissue around the lungs, heart, or abdomen, or
under the skin.
- 1 out of every 1,000 births.
110. COMPLICATIONS
Bone problems: "hair on end" appearance
of the skull, prominence of the upper incisors.
These changes contribute to the classic
hemolytic/ chipmunk facies.
Osteoporosis and osteopenia may result in
fractures; the child may need treatment with
calcium, vitamin D and bisphosphonates to
improve bone density. 2/13/2023 110
111. OTHER COMPLICATIONS
Extramedullary hematopoiesis: This usually occurs in patients with
thalassemia intermedia who are not receiving transfusion therapy.
They may cause neuropathy or paralysis from compression of the spine
or peripheral nerves.
Compression fractures and paravertebral expansion of extramedullary
masses, which behave like tumors, are seen during the second decade of
life.
2/13/2023 111
112. OTHER COMPLICATIONS
Psychosocial: as these children survive into adulthood, problems related
to employment, marriage and having families, as well as the stress of
chronic illness will need to be addressed.
2/13/2023 112
113. CURE OF THALASSEMIA MAJOR
Hematopoietic stem cell transplantation (HSCT) Is the only known
curative treatment for thalassemia.
Poor outcome of HSCT occurs in patient with hepatomegaly, portal
fibrosis and inadequate chelation prior to transplant.
The event-free survival rate for patients who have all three features is
59%, compared to 90% for those who do not.
2/13/2023 113
115. HEMATOPOIETIC STEM CELL TRANSPLANTATION
Bone marrow transplantation (BMT) is more correctly called hematopoietic stem cell
transplantation (HSCI).
This is an established life-saving procedure for a number of malignant and non-malignant
diseases.
Types:
(1) Autologous transplant-when the source of stem cells is harvested from the patient and
(2) Allogenek transplant-when stem cells are collected from a human leukocyte antigen
(HLA) matched sibling or unrelated donor.
The commonly used sources of hematopoietic stem cells are cytokine mobilized peripheral
blood, bone marrow and umbilical cord blood.
2/13/2023 115
116. SICKLE CELLANEMIA
Occurs in India with a gene
frequency of 4.3%, is relatively
common in multiple states
including Odisha, Maharashtra,
Madhya Pradesh, Jharkhand and
Gujarat.
2/13/2023 116
117. PREVALENCE
The Ministry of Health estimates that 2,000 Tharu people have sickle cell anemia
throughout the country, with heavy prevalence in the midwestern and farwestern
regions of the nation, where more than 1,300 people have been diagnosed since 2011.
According to the 2011 census, there are 1.74 million Tharus in Nepal.
2/13/2023 117
120. PATHOPHYSIOLOGY
Sickle cell anemia, an autosomal recessive disease, results from the substitution of
valine for glutamic acid at position 6 of the beta-globin gene.
2/13/2023 120
121. PATHOPHYSIOLOGY
Sickle red cells obstruct the microcirculation, resulting in tissue hypoxia that
perpetuates sickling.
The affected cells are rapidly hemolyzed and have a lifespan of app 10-20
days.
2/13/2023 121
126. TYPES OF CRISIS
i. Vaso-occlusive crisis
- this crisis occurs when the microcirculation is obstructed by sickled red cells,
resulting in ischemic injury.
- Pain is the chief complaint; bones (e.g. femur, tibia and lower vertebrae) are
frequently involved.
- Vaso-occlusion may present as dactylitis or as hand and foot syndrome (painful
swollen hands and/ or feet in children).
- Vaso-occlusion may mimic an acute abdomen. The spleen develops auto infarcts and
becomes fibrotic.
2/13/2023 126
127. VASO-OCCLUSIVE CRISIS
In the kidney, it results in papillary necrosis, which results in papillary necrosis,
which results in isosthenuria (inability to concentrate urine).
Vaso-occlusive crisis can involve the lungs and cause acute chest syndrome; retinal
hemorrhages in the eye and involvement of corpus cavernosum, leading to
priapism.
Involvement of the femoral head results in avascular necrosis.
Cerebrovascular accidents may occur in children, and trend to be recurrent.
2/13/2023 127
128. TYPES OF CRISIS
ii. Acute chest syndrome: this is a vaso-occlusive crisis, with chest pain, cough,
tachypnea, dyspnea, hypoxemia and fever. The condition requires hospitalization with
need for IV fluids, oxygen, bronchodilators and antibiotics (including for Mycoplasma
and Chlamydia).
iii. Sequestration crisis: sickle cells block splenic outflow and pooling of blood in the
engorged spleen, resulting in splenic sequestration.
2/13/2023 128
129. TYPES OF CRISIS
iv. Risk of infection: Patients are susceptible to infection with encapsulated organisms
(H. influenzae, S. pneumoniae) and other microbes (Salmonella, Mycoplasma, S.
aureus, E. colz).
iv. Aplastic crisis: Aplastic crisis occurs when the bone marrow stops producing red
blood cells, following an infection (often parvovirus B19) or associated with folate
deficiency.
The condition is self-limited; supportive care and packed red cell transfusions are
required.
2/13/2023 129
130. LABORATORY STUDIES
Anemia and thrombocytosis are commonly found.
While Leukocytosis is common, white cell count
>20000/mm3 with a shift to the left indicates infection.
On peripheral smear, sickle-shaped red cells are found
along with target cells.
Presence of Howell-Jolly bodies indicates functional
asplenia.
The indirect bilirubin level may be elevated
2/13/2023 130
131. LABORATORY STUDIES
If the diagnosis of sickle cell anemia has not been made, the sickling test establishes
the presence of HbS.
Hemoglobin electrophoresis
2/13/2023 131
132. ASSESSMENT DURING ACUTE ILLNESS
In a sick child, blood type and crossmatch is required for probable transfusion.
X-ray of the chest and bones, and blood culture may be indicated.
Monitoring of oxygen saturation and arterial blood gases should be advised in
patients in respiratory distress.
A drop in hemoglobin exceeding 2 g/ dL from baseline indicates splenic
sequestration or aplastic crisis; the reticulocyte count and examination of spleen size
help differentiate these conditions.
An electrocardiogram is performed, if patient has chest pain and/ or irregular pulse.
2/13/2023 132
133. HOSPITAL MANAGEMENT
Hydration and analgesia are the mainstays of treatment in pain crisis.
Oral hydration is preferred, if the patient is not vomiting and can tolerate oral fluids.
Narcotic analgesia is frequently used.
Patients with severe dehydration should receive IV fluids.
Blood transfusion is required in patients with aplastic and sequestration crisis.
2/13/2023 133
134. HOSPITAL MANAGEMENT
Intubation and mechanical ventilation, exchange transfusion may be required, if
cerebrovascular accidents have occurred, or with acute chest syndrome.
Exchange transfusion consists of replacing the patient red cells by normal red cells,
decreasing sickle hemoglobin (HbS).
Bone marrow transplant.
2/13/2023 134
135. FACILITIES IN NEPAL
Bipanna Nagarik Kosh was started after the Janandolan of 2062 BS. With the country
slowly recovering from the decade long armed conflict, this Koshi was established to
provide some financial relief to people from difficult and expensive diseases.
Cardiovascular diseases, Cancer, Renal failure, Alzheimer's disease, Parkinson's
disease, Head and Spinal injury, Sickle Cell Anaemia and Stroke are covered under
this program.
2/13/2023 135
136. FACILITIES IN NEPAL
Those eligible to claim services under the Bipanna Nagarik Koshi will receive the
following:
1. Each patient will be provided NRs. 1,00,000/- as health care expense including
medicines required for disease management
2. For patients with renal impairment (मृगौला रोगीको उपचार सम्बन्धमा)
3. Free haemodialysis and peritoneal dialysis for 1 year
4. NRs. 2,00,000/- as kidney transplant expense
5. NRs. 1,00,000/- in one or more instalments as medicine expense for post-transplant
management
6. NRs. 1,00,000 to purchase medicine post kidney transplant is provided as cash grant. All
other subsidies are provided directly through hospitals in Nepal. 2/13/2023 136
137. FACILITIES IN NEPAL IN LISTED HOSPITAL FOR SCD
1. Bheri Zonal Hosppital, Banke
2. Lumbini Zonal hospital, Butwal
3. Seti Zonal Hospital, Kailali
4. Mahakali Zonal Hospital, Kanchanpur Mahakali
5. District Hospital, Kapilbasthu
6. District Hospital, Nawalparashi
7. District Hospital, Bardiya
2/13/2023
137
138. PREVENTIVE CARE
All children require prophylaxis with penicillin/ amoxicillin, at least until 5 years of age.
They should receive the pneumococcal, meningococcal and Hemophilus vaccines.
They should also receive lifelong folate supplements.
Hydroxyurea, that increases HbF and reduces episodes of pain crises, stroke and acute chest
syndrome, is recommended to be given at a daily dose of 10-15 mg/kg/day.
Children on hydroxyurea should be monitored with complete blood counts. Patients need to
be screened for gallstones and stroke.
Genetic counseling and testing should be offered to the family. Parents need to learn to
identify complications.
2/13/2023 138
139. APLASTIC ANEMIA
Aplastic anemia is a group of inherited or acquired disorders of the hematopoietic
stem cells.
The prevalence of bone marrow failure resulting from hypoplastic or aplastic anemia
is 2-6 cases per million in Western literature.
In India, the prevalence is higher.
2/13/2023 139
146. TREATMENT
Supportive care such as packed red cells for anemia, platelets for thrombocytopenia
and antibiotics for infection is needed.
Hematopoietic stem cell transplant (HSCT) is the only curative therapy.
Criteria for referral for HSCT is:
(i) patients who are young (<50 years)
(ii) severe aplastic anemia, and
(iii) a matched related sibling donor.
Patients with severe acquired aplastic anemia who cannot undergo HSCT may benefit
from therapy with antithymocyte globulin (ATG) or anti-lymphocyte globulin (ALG)
and cyclosporine. 2/13/2023 146
147. TREATMENT
Anti-thymocyte globulin (ATG) is an infusion of horse or rabbit-derived antibodies
against human T cells, which is used in the prevention and treatment of acute
rejection in organ transplantation and therapy of aplastic anemia.
Anti-lymphocyte globulin (ALG) is an infusion of animal- antibodies against human
T cells which is used in the treatment of acute rejection in organ transplantation.
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148. PROGNOSIS
Severe anemia can result in high-output cardiac failure/ neutropenia can lead to
bacterial and fungal infections; severe bleeding can occur due to thrombocytopenia.
The severity and extent of cytopenia determine prognosis.
With current HSCT regimens, most patients with severe aplastic anemia show 60-
70% long-term survival; better survival is reported in favorable subgroups.
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150. REFERENCES
Ghai O, Paul V, Bagga A. Essential Pediatrics. 7th ed. CBS Publisher & Distributers;
2008.
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Editor's Notes
Lassitude: a state of physical or mental weariness; lack of energy.
A cardiac or vascular murmur heard in anemic persons who have no valvular lesion.
Bruit, also called vascular murmur, is the abnormal sound generated by turbulent flow of blood in an artery due to either an area of partial obstruction or a localized high rate of blood flow through an unobstructed artery.
Humming: make a low, steady continuous sound like that of a bee
The main hematinics are iron, B12, and folate. Deficiency in hematinics can lead to anaemia.
Spherocytosis is the presence in the blood of spherocytes, i.e erythrocytes (red blood cells) that are sphere-shaped rather than bi-concave disk shaped as normal.
It's the average amount in each of your red blood cells of a protein called hemoglobin, which carries oxygen around your body.
Abnormal red cell indices can exist in subjects even when the underlying disorder is not sufficiently severe to cause anemia.
Polychromasia is the presentation of multicolored red blood cells in a blood smear test.
The direct Coombs test is used to test for autoimmune hemolytic anemia—that is, a condition where the immune system breaks down red blood cells, leading to anemia.
Reticulocytes are immature red blood cells.
is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
Narrowing of oesophagus
Iron absorption is reduced in the presence of non-nutritive substances. Iron therapy usually cures the pica behavior. There are different forms of pica, one caused directly by iron deficiency probably due to the lack of iron in some areas of the brain and one more culturally driven and including mostly geophagy.
The peripheral smear shows that red cells are microcytic and hypochromic, with anisocytosis, poikilocytosis and increased red cell distribution width (RDW).
The MCV and MCHC are reduced. Red cell number is reduced, unlike in thalassemia where it is increased.
Serum iron is reduced, total iron binding capacity (TIBC) is increased and transferrin is reduced to less than 16% {normal 25-50%).
The reduction in serum ferritin occurs early, and correlates with total body iron stores. Ferritin, an acute phase reactant, is elevated in inflammatory conditions, and may thus be falsely high in a sick child.
Enteric-coated preparations have fewer side effects, but are also less efficacious and more expensive.
Generally, 50-65 mg of elemental iron, given three to four times per day, for a total of 200-300 mg of iron is needed for replacement therapy.
Immature cells
One carbon reaction: mediated by the folate co factor, is a group of biochemical reactions with a special set of enzymes and co-enzymes.
(e.g. celiac. disease, malabsorption states)
(e.g. methotrexate, 6-mercapptopurine, trimethoprim, azathioprine, phenytoin),
(e.g. infancy, hyperthyroidism, chronic hemolytic disease).
In infants, it is related to maternal deficiency with inadequate body stores and prolonged exclusive breastfeeding (breast milk is a poor source of vitamin B12 and associated with reduced access to other foods).
Giardia infection is shown to cause folate malabsorption.
H. pylori infections are implicated in vitamin B12 malabsorption in adults.
Rarely inherited metabolic disorders may cause megaloblastic anemia.
History of medication intake, medical disorders and infestation needs to be taken.
All 3 blood cells decrease (WBC, RBC, Platelets)
Loss of movement/ body position
Cytopenia is a reduction in the number of mature blood cells. It is common in cancer patients being treated with radiation and/or chemotherapy.
The Schilling test is a medical procedure used to determine whether you're absorbing vitamin B-12 properly.
In megaloblastic anemia the bone marrow will be cellular and show, red blood cell precursor nuclear-cytoplasmic asynchrony.
Granulocyte precursors may also be abnormal.
(pure red cell aplasia, transient erythroblastopenia of childhood), (e.g. myelodysplastic syndromes)
myeloid progenitor
March hemoglobinuria is a condition in which physical exertion in the upright position gives rit:ie to the passage of red urine containing hemoglobin in solution.
Abetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet.
Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system.
Hypersplenism is an overactive spleen
Because the reticulocyte count is expressed as a percentage of total RBCs, it must be corrected according to the extent of anemia with the following formula: reticulocyte % × (patient Hct/normal Hct) = corrected reticulocyte count.
and implies that the erythrocyte is coated with IgG or C3 component of complement. However the test may be negative in 2-5% of patients with immune hemolysis.
(when chains are needed to pair with chains to form HbA, after chains production is turned off).
The condition may not be recognized because of the delay in cessation of HbF production till 3-5 years of age in some cases.
Polychromasia is the presentation of multicolored red blood cells in a blood smear test.
, but is marked in patients receiving irregular or adequate transfusion support.
Target cells, or codocytes, have an excess of cell membrane relative to cell volume
In thalassemia major and intermedia, the hemoglobin level ranges from 2-8 g/ dL; MCV and MCH are significantly low.
Reticulocyte count is elevated to 5-8% and leukocytosis is usually present.
The platelet count is usually normal, unless the spleen is markedly enlarged and causing hypersplenism.
Peripheral blood film reveals hypochromia and microcytosis.
Hemochromatosis is a disorder where too much iron builds up in your body. Sometimes it's called “iron overload.”
Iron preparations as hematinic or dietary supplements should not be given. Drinking tea with meals has been shown to decrease absorption of iron in the gut
Very high transferrin saturation in patients with iron overload affects the bacteriostatic properties of the protein, resulting in increased risk of infections with Y. enterocolitica that presents with fever and diarrhea. Other important infections which may occur are mucormycosis and Listeria monocytogenes.
Other investigations include liver biopsy, liver MRI and echocardiography. An accurate and noninvasive tool to assess cardiac iron status is cardiac T2 * magnetic resonance (CMR).
This chelator is highly selective for iron and chelates both intracellular and extracellular excess iron.
.
1,. One missing or abnormal gene makes a child a silent alpha thalassemia carrier. Silent alpha thalassemia carriers have no signs or symptoms of the disease, but are able to pass thalassemia on to their children
2. Two missing or mutated genes is a condition called alpha thalassemia minor or having alpha thalassemia trait. Children with this condition may have red blood cells that are smaller than normal (microcytosis) and sometimes very slight anemia.
People with alpha thalassemia minor usually don't have any symptoms at all, but can pass thalassemia on to their children. The two abnormal genes can be on the same chromosome (called the cis position) or one on each chromosome (called the trans position). If two genes on the same chromosome are affected, the person can pass along a two-gene defect to his or her child. This situation is much more common in people of Asian descent.
3. Three missing or mutated genes is called hemoglobin H disease. Signs and symptoms will be moderate to severe.
4. Four missing or mutated genes is a condition known as alpha thalassemia major or hydrops fetalis. This almost always leads to a fetus dying before delivery or a newborn baby dying shortly after birth. However if this disease is suspected because of a history in the family, it can be diagnosed prenatally. Sometimes, if treatment is initiated before the baby is even born, the baby can survive.
severe anemias, including thalassemia
fetal bleeding (hemorrhage)
heart or lung defects in the baby
genetic and metabolic disorders, including Turner syndrome and Gaucher’s disease
viral and bacterial infections, such as Chagas disease, parvovirus B19, cytomegalovirus (CMV), toxoplasmosis, syphilis, and herpes
vascular malformations
tumors
Extramedullary hematopoiesis (EH) is defined as hematopoiesis occurring in organs outside of the bone marrow; it occurs in diverse conditions, including fetal development, normal immune responses, and pathological circumstances.
The main difference between a stem cell and bone marrow transplant is whether stem cells are collected from the bloodstream or bone marrow.
A stem cell transplant uses stem cells from your bloodstream, or a donor’s bloodstream. This is also called a peripheral blood stem cell transplant.
A bone marrow transplant uses stem cells from your bone marrow, or a donor’s bone marrow.
Stem cell transplants are the most common type of transplant. Bone marrow transplants are not used as much. This is because:
it’s easier to collect stem cells from the bloodstream than bone marrow
your treatment team can usually collect more cells from the bloodstream
blood counts tend to recover quicker following a stem cell transplant
HBB: beta globin gene
SC Trait : NO chance of getting malaria (plasmodium falciparium.
Malarial parasites invade normal red blood cells and rearrange their content. The parasites breed and produce proteins that make red blood cells sticky. These blood cells explode, releasing parasites capable of infecting other red blood cells.
The misshapen hemoglobin of SCT affects a parasite’s ability to complete this cycle. The parasite triggers the SCT hemoglobin to sickle. The immune system then clears the infected red blood cells before the parasite can complete its life cycle and infect other red blood cells. This means fewer parasites and milder illness
make (something) continue indefinitely
papillary necrosis is a form of nephropathy involving the necrosis of the renal papilla.
Corpus cavernosum: either of two masses of erectile tissue forming the bulk of the penis and the clitoris. The two corpora cavernosa and corpus spongiosum (also known as the corpus cavernosum urethrae in older texts and in the adjacent diagram) are three expandable erectile tissues along the length of the penis, which fill with blood during penile erection.
Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism.
Target cell: abnormal RBC
Sickle hemoglobin
differentiates individuals who are homozygous from the heterozygous.
The former will have high levels of HbSS (80-90%); carriers have lower levels (35-40%). These samples should be taken before blood transfusion.
Hypoxia
Dehydration
acidosis
Plastic: formation and synthesis
Failure of bone marrow stem cells
Myeloid dysplastic Syndrome: MDS = MCV high
Precursor cell high, when bone marrow is functioning, those precursor cell increases but does not get matured. Thus MCV is high.
Cytopenia is a reduction in the number of mature blood cells.