Breif information about haemolytic anaemia in children

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3.  Hemolysis is the premature destruction of erythrocytes.
 A hemolytic anemia will develop if bone marrow activity
cannot compensate for the erythrocyte loss.
 The severity of the anemia depends on whether the onset
of hemolysis is gradual or abrupt and on the extent of
erythrocyte destruction.
 Mild hemolysis can be asymptomatic while the anemia in
severe hemolysis can be life threatening and cause angina
and cardiopulmonary decompensation.
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4.  Hemolysis can be due to hereditary and acquired
disorders.
 The etiology of premature erythrocyte destruction
is diverse and can be due to conditions such as:
1. Intrinsic membrane defects.
2. Abnormal hemoglobins.
3. Erythrocyte enzymatic defects.
4. Immune destruction of erythrocytes.
5. Mechanical injury.
6. Hypersplenism.
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5.  Hemolysis may be an extravascular or an
intravascular phenomenon.
 Autoimmune hemolytic anemia and
hereditary spherocytosis are examples of
extravascular hemolysis because the red
blood cells are destroyed in the spleen
and other reticuloendothelial tissues.
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6.  Intravascular hemolysis occurs in hemolytic anemia
due to one of the following:
1. Prosthetic cardiac valves.
2. Glucose-6-phosphate dehydrogenase (G6PD)
deficiency.
3. Thrombotic thrombocytopenic purpura.
4. Disseminated intravascular coagulation.
5. Transfusion of ABO incompatible blood.
6. Paroxysmal nocturnal hemoglobinuria
(PNH).=78/9+
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7.  Hemolysis may also be intramedullary, when fragile
red blood cell (RBC) precursors are destroyed in the
bone marrow prior to release into the circulation.
Intramedullary hemolysis occurs in pernicious
anemia and thalassemia major.
 Hemolysis is associated with a release of RBC
lactate dehydrogenase (LDH).
 Hemoglobin released from damaged RBCs leads to
an increase in indirect bilirubin and urobilinogen
levels.
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8.  A patient with mild hemolysis may have
normal hemoglobin levels if increased RBC
production matches the rate of RBC
destruction. However, patients with mild
hemolysis may develop marked anemia if their
bone marrow erythrocyte production is
transiently shut off by viral (parvovirus B-19)
or other infections. This scenario would be an
aplastic crisis since the bone marrow can no
longer compensate for ongoing hemolysis.
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9.  Skull and skeletal deformities can occur in
childhood due to a marked increase in
hematopoiesis and resultant bone marrow
expansion in disorders such as thalassemia.
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10.  Hereditary disorders may cause hemolysis as a
result of :
1. Erythrocyte membrane abnormalities such as :
A. Hereditary spherocytosis
B. Hereditary elliptocytosis
2. Enzymatic defects such as:
a. Glucose-6-phosphate dehydrogenase (G6PD)
deficiency
b. Pyruvate kinase deficiency
3. Hemoglobin abnormalities such as:
a) Sickle cell anemia
b) Thalassaemia
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12.  Sickle cell disease (SCD) and its
variants are genetic disorders resulting
from the presence of a mutated form of
hemoglobin, hemoglobin S (HbS).
 Morbidity, frequency of crisis, degree
of anemia, and the organ systems
involved vary considerably from
individual to individual.
 An autosomal recessive disorder first
described by Herrick in 1910.
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14.  Infants are protected largely by elevated levels of Hb F. Sickle
cell disease (SCD) usually manifests early in childhood, the
condition becomes evident, as follows:
1. Acute and chronic pain : The most common clinical
manifestation of SCD is vaso-occlusive crisis; pain crises are
the most distinguishing clinical feature of SCD.
2. Bone pain : Often seen in long bones of extremities primarily
due to bone marrow infarction.
3. Anemia : Universally present, chronic, and hemolytic in nature.
4. Aplastic crisis : Serious complication due to infection with B19
virus.
5. Splenic sequestration : Characterized by the onset of life-
threatening anemia with rapid enlargement of the spleen and
high reticulocyte count.
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15.  Infection: Organisms that pose the greatest danger
include encapsulated respiratory bacteria, particularly
Streptococcus pneumonae; adult infections are
predominately with gram-negative organisms, especially
Salmonella.
 Growth retardation, delayed sexual maturation, being
underweight
 Hand-foot syndrome: This is a dactylitis presenting as
bilateral painful and swollen hands and/or feet in children.
 Acute chest syndrome: Young children present with chest
pain, fever, cough, tachypnea, leukocytosis, and
pulmonary infiltrates in the upper lobes; adults are usually
afebrile, dyspneic with severe chest pain, with
multilobar/lower lobe disease.
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17.  Pulmonary hypertension: Increasingly recognized as a serious
complication of SCD.
 Avascular necrosis of the femoral or humeral head: due to vascular
occlusion.
 CNS involvement: Most severe manifestation is stroke.
 Ophthalmologic involvement: Ptosis, retinal vascular changes,
proliferative retinitis.
 Cardiac involvement: Dilation of both ventricles and the left atrium.
 GI involvement: Cholelithiasis is common in children; liver may
become involved.
 GU involvement: Kidneys lose concentrating capacity; priapism is a
well-recognized complication of SCD.
 Dermatologic involvement: Leg ulcers are a chronic painful problem.
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18.  Triggers of vaso-occlusive crisis include the
following:
1. Hypoxemia: May be due to acute chest syndrome or
respiratory complications.
2. Dehydration: Acidosis results in a shift of the
oxygen dissociation curve to the right.
3. Changes in body temperature (e.g., an increase due
to fever or a decrease due to environmental
temperature change).
 Many individuals with HbSS experience chronic low-
level pain, mainly in bones and joints. Intermittent
vaso-occlusive crises may be superimposed, or
chronic low-level pain may be the only expression of
the disease.
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19.  Hemoglobin electrophoresis.
 CBC count with differential and
reticulocyte count.
 Serum electrolytes.
 Hemoglobin solubility testing.
 Peripheral blood smear.
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22.  Pulmonary function tests (transcutaneous Oxygen
saturation)
 Renal function (creatine, BUN, urinalysis).
 Hepatobiliary function tests, (ALT, fractionated
bilirubin).
 CSF examination: Consider LP in febrile children
who appear toxic and in those with neurologic
findings (e.g., neck stiffness, positive Brudzinski /
Kernig signs, focal deficits); consider CT scanning
before performing LP.
 Blood cultures.
 ABGs.
 Secretory phospholipase A2 (sPLA2).
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23.  Radiography: Chest x-rays should be performed in
patients with respiratory symptoms.
 MRI: Useful for early detection of bone marrow changes
due to acute and chronic bone marrow infarction,
marrow hyperplasia, osteomyelitis, and osteonecrosis.
 CT scanning: May demonstrate subtle regions of
osteonecrosis not apparent on plain radiographs and to
exclude renal medullary carcinoma in patients
presenting with hematuria.
 Nuclear medicine scanning: 99m Tc* bone scanning
detects early stages of osteonecrosis; 111 In** WBC
scanning is used for diagnosing osteomyelitis.
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24.  Transcranial Doppler ultrasonography: Can identify
children with SCD at high risk for stroke.
 Abdominal ultrasonography: May be used to rule out
cholecystitis, cholelithiasis, or an ectopic pregnancy
and to measure spleen and liver size.
 Echocardiography: Identifies patients with pulmonary
hypertension.
 Transcranial near-infrared spectroscopy or cerebral
oximetry: Can be used as a screening tool for low
cerebral venous oxygen saturation in children with
SCD.
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25.  The goals of treatment in SCD are symptom control and
management of disease complications. Treatment strategies
include :
1. Management of vaso-occlusive crisis.
2. Management of chronic pain syndromes.
3. Management of chronic hemolytic anemia.
4. Prevention and treatment of infections.
5. Management of the complications and the various organ
damage. syndromes associated with the disease.
6. Prevention of stroke.
7. Detection and treatment of pulmonary hypertension.
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26.  Antimetabolites: Hydroxyurea
 Nonsteroidal analgesics (e.g., ketorolac, aspirin,
acetaminophen, ibuprofen)
 Antibiotics (e.g., cefuroxime, amoxicillin/
clavulanate, penicillin VK, ceftriaxone,
azithromycin, cefaclor)
 Vaccines (e.g., pneumococcal, meningococcal,
influenza, and recommended scheduled
childhood/adult vaccinations
 Vitamins (e.g., folic acid)
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27.  Hemoglobin oxygen-affinity modulators (eg, voxelotor).
 P-selectin inhibitors (eg, crizanlizumab).
 Opioid analgesics (eg, oxycodone/aspirin, methadone,
morphine sulfate, oxycodone/acetaminophen, fentanyl,
nalbuphine, codeine).
 Tricyclic antidepressants (eg, amitriptyline).
 Endothelin-1 receptor antagonists (eg, bosentan).
 Phosphodiesterase inhibitors (eg, sildenafil, tadalafil).
 L-glutamine.
 Antiemetics (eg, promethazine).
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28.  Other approaches to managing SCD include the
following:
1. Stem cell transplantation: Can be curative.
2. Transfusions: For sudden, severe anemia due to acute
splenic sequestration, parvovirus B19 infection, or
hyperhemolytic crises.
3. Wound debridement.
4. Physical therapy.
5. Heat and cold application.
6. Acupuncture and acupressure.
7. Transcutaneous electric nerve stimulation (TENS).
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29.  Vigorous hydration (plus analgesics):
For vaso-occlusive crisis
 Oxygen, antibiotics, analgesics,
incentive spirometry, simple
transfusion, and bronchodilators: For
treatment of acute chest syndrome
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31.  Of genetic disorders worldwide, thalassemia syndromes are
among the most common.
 Normal adult hemoglobin produced after birth (hemoglobin
A [HbA]) consists of a heme molecule linked to two α-globin
and two β-globin chains (α2β2), with α-globin chain
production dependent on four genes on chromosome 16,
and β-globin chain production arising from two genes on
chromosome 11.
 Deletions or mutations of one or more of these genes so
that the rate of production of α- or β-globin chains is
reduced results in alpha thalassemia or beta thalassemia,
respectively.
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32.  Thalassemia is usually asymptomatic in
carriers, or presents with anemia of varying
degrees in patients in whom globin-chain
production is more severely impaired.
 Patients with alpha-thalassemia trait or beta-
thalassemia trait are asymptomatic but have
mild microcytic hypochromic anemia, which
often goes undiagnosed or is confused with iron
deficiency anemia.
 Recognizing the possibility of thalassemia trait
by taking a complete family history and
appropriate testing is important in making an
accurate diagnosis.
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33.  Pallor.
 Icterus.
 Enlarged abdomen due to
hepatospllenomegally.
 Severe bony due to ineffective erythroid
production. (frontal bossing, prominent facial
bones, dental malocclusion).
 Nuropathy/paralysis due to extra medullary
haematopoisis.
 Growth retardation and short stature.
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35. 1.&2. CBC and PBF: The diagnosis of beta
thalassemia minor usually is suggested by the
presence of the following:
A. Mild, isolated microcytic anemia
B. Target cells on the peripheral blood smear
C. A normal red blood cell (RBC) count
3. Electrophoresis
4. Globin chain assay
5. PCR
6. Moreover sensitivity to next generation
sequencing (NGS) allowed noninvasive screening to
be done on fetal DNA obtained from maternal blood.
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36. microcytes (M), target cells (T), and poikilocytes (P).
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37. more marked microcytosis (M) and anisopoikilocytosis (P) than in
thalassemia minor. Target cells (T) and hypochromia are prominent.
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38.  Splenoectomy.
 Repeated blood transfusion.
 Routine administration of iron
chelation agent.
 Gene therapy (Zynteglo).
 Bone marrow transplantation.
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40.  Hereditary spherocytosis (HS) is a familial
hemolytic disorder associated with a
variety of mutations that lead to defects in
red blood cell (RBC) membrane proteins.
 The morphologic hallmark of HS is the
microspherocyte, which is caused by loss
of RBC membrane surface area and has
abnormal osmotic fragility in vitro.
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41.  HS shows marked heterogeneity, ranging from
an asymptomatic condition to fulminant
hemolytic anemia.
 Patients with severe cases may present as
neonates, while those with mild HS may not
come to medical attention until adulthood, when
an environmental stressor uncovers their
disorder.
 The major complications of HS are aplastic or
megaloblastic crisis, hemolytic crisis, and
cholecystitis and cholelithiasis.
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42.  The principal laboratory studies to diagnose (HS)
include :
1. Complete blood cell count
2. Reticulocyte count
3. Mean corpuscular hemoglobin concentration (MCHC)
4. Peripheral blood smear
5. Lactate dehydrogenase (LDH) level
6. Haptoglobin
7. Fractionated bilirubin
8. Combs testing
9. Flow cytometry using the eosin-5'-maleimide (EMA)
binding test
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43.  The classic laboratory features of HS include the
following:
1. Mild to moderate anemia.
2. Reticulocytosis.
3. Increased mean corpuscular hemoglobin
concentration (MCHC).
4. Spherocytes on the peripheral blood smear.
5. Hyperbilirubinemia.
6. Abnormal results on the incubated osmotic
fragility test.
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44.  RBC morphology in HS is distinctive yet not diagnostic.
Anisocytosis is prominent, and the smaller cells are
spherocytes. Unlike the spherocytes associated with immune
hemolytic disease and thermal injury, HS spherocytes are
fairly uniform in size and density.
 Spherocytes are characterized by the following:
1. Lack of central pallor
2. Decreased mean corpuscular diameter
3. Increased density.
 Spherocytic RBCs are not specific to HS. Autoimmune
hemolytic anemia also may produce spherocytosis, but this
disorder usually can be excluded by negative findings on a
direct antiglobulin test.
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46.  Splenectomy is the standard treatment for
patients with clinically severe HS, but can
be deferred safely in patients with mild
uncomplicated HS (hemoglobin level >11
g/dL).
 Splenectomy usually results in full control
of HS, except in the unusual autosomal
recessive variant of the disorder.
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48.  Glucose-6-phosphate dehydrogenase (G6PD)
deficiency is the most common enzyme deficiency in
humans, affecting 400 million people worldwide.
 It has a high prevalence in persons of African, Asian,
and Mediterranean descent. It is inherited as an X-
linked recessive disorder.
 G6PD deficiency is polymorphic, with more than 300
variants.
 G6PD deficiency confers partial protection against
malaria, which probably accounts for the persistence
and high frequency of the responsible genes.
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49.  G6PD deficiency can present as neonatal
hyperbilirubinemia.
 Persons with this disorder can experience
episodes of brisk hemolysis after ingesting
fava beans or being exposed to certain
infections or drugs.
 Less commonly, they may have chronic
hemolysis. However, many individuals with
G6PD deficiency are asymptomatic.
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50.  Complete blood cell count (CBC) and
reticulocyte count
 Lactate dehydrogenase (LDH) level
 Indirect and direct bilirubin level
 Serum haptoglobin level
 Urinalysis for hematuria
 Urinary hemosiderin
 Peripheral blood smear
 Standard tests include the Beutler test and a
quantitative assay of GPD activity.
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51. Heinz bodies are denatured haemoglobin, which occurs in
G6PD deficiencies and in unstable haemoglobin disorders.
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52.  Most individuals with G6PD deficiency do
not need treatment. However, they should
be taught to avoid drugs and chemicals
that can cause oxidant stress.
 Infants with prolonged neonatal jaundice
as a result of G6PD deficiency should
receive phototherapy with a bili light
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54.  Autoimmune hemolytic anemia (AIHA) can be
due to warm or cold autoantibody types and,
rarely, mixed types.
 Most warm autoantibodies belong to the
immunoglobulin IgG class. These antibodies
can be detected by a direct Coombs test, which
also is known as a direct antiglobulin test (DAT).
 AIHA may occur after allogeneic hematopoietic
stem cell transplantation.
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55.  AIHA is rare in children and has a range of
causes.
 Autoimmune hemolysis can be primary or
secondary to conditions such as infections
(viral, bacterial, and atypical), systemic lupus
erythematosis (SLE), autoimmune hepatitis
(AIH), and H1N1 influenza.
 H1N1 influenza–associated AIHA in children
may respond to treatment with Oseltamivir and
intravenous immunoglobulin.
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56.  Fetal splenomegaly and associated
hepatomegaly could be due to hemolysis,
but infections are the most likely cause.
 Congestive heart failure and metabolic
disorders should be considered in any
child with splenomegaly.
 Rarely, leukemia, lymphoma, and
histiocytosis are associated with
splenomegaly.
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57.  Microangiopathic hemolytic anemia,
which results in the production of
fragmented erythrocytes (schistocytes),
may be caused by any of the following :
1. Defective prosthetic cardiac valves
2. Disseminated intravascular coagulation
(DIC)
3. Hemolytic uremic syndrome (HUS)
4. Thrombotic thrombocytopenic purpura
(TTP)
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58. is a fragmented part of a red blood cell. Schistocytes are
typically irregularly shaped, jagged, and have two pointed ends
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59. TANK YOU
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