Approach to a Child

with Pallor
Roudha Aljabri
Rawan Albusaidi
Outline
Introduction and background
Causes of Pallor
History and Physical Examination
Labs and Investigations
Pallor
• unusual lightness of skin color compared to a normal complexion, due to the reduced amount of
oxyhemoglobin or decreased peripheral perfusion
• occasionally first noted by someone who sees the child less often than the parents
• can be acute and associated with a life-threatening illness, or it can be chronic and subtle
Classification of anemia based on RBC
size
 Causes
Decreased erythrocyte or III
I Blood loss
hemoglobin production

Increased erythrocyte
II destruction
IV Non-Hematologic
 Causes of anemia in infants and
children:
✔ Parvovirus B19 infection
✔ Daimond-blackfan anemia
✔ Transient erythroblastopenia of
Red cell aplasia
childhood
✔ Rarities: fanconi anemia, aplastic
Impaired red cell anemia, leukemia
production
✔ Iron deficiency anemia
✔ Folic acid deficiency
Ineffective ✔ Chronic inflammation
erythropoiesis ✔ Chronic renal failure
✔ Rarities: myelodysplasia, lead
poisoning
 Causes of anemia in infants and
children:

Red cell membrane ✔ Hereditary spherocytosis

disorder

✔ SCD, thalacemia
Hemogobinopathies

Increased cell
destruction
Red cell enzyme
✔ G6PD deficiency
disorder

✔ Hemolytic anemia of
Immune response newborn
✔ Autoimmune hemolytic
anemia
 Causes of anemia in infants and
children:

Chronic GI blood loss ✔ Meckel’s diverticulum

Blood loss

Inherited bleeding
✔ Von willebrand’s disease
disorders
Sickle Cell
• Autosomal recessive
• Main forms:
• Sickle cell anemia HbSS
• Sickle cell disease HbSC
• Sickle β-thalassemia
• Sickle cell trait
• Clinical feature:
• Presents after 6 months of age
• Anemia: usually Hb (6–10 g/dl) with clinically
detectable jaundice
• Infections:
• Increase in susceptibility to infection
(pneumococci and Haemophilus influenzae)
• Osteomyelitis caused by Salmonella and other
organisms
Investigations
• CBC:
• Hb 6-8 g/dL
• High reticulocyte count
• Blood film:
• Sickled cells
• SICKLEDEX test
• Hb Electrophoresis
• HPLC (High-performance liquid chromatography)
Management
• Prophylaxis: • Treatment of acute crises:
• Immunization (pneumococcal, Hemophilus • Oral or intravenous analgesia
influenzae type B and meningococcus) • Good hydration (oral or intravenous as
• Daily oral penicillin: to ensure the full required)
coverage • Antibiotics
• Daily oral folic acid • Oxygen should be given if the oxygen
• Avoid exposure to cold, dehydration, saturation is reduced.
excessive exercise, stress or hypoxia. • Exchange transfusion is indicated for acute
chest syndrome, strokes and priapism.
Thalassemia
• Thalassemias are a group of hereditary
hemoglobin disorders characterized by
mutations on the α- or β-globin chains
(resulting in alpha or beta thalassemia).
• Alpha thalassemia: most commonly seen
in people of Asian and African descent.
• Beta thalassemia: most commonly seen in
people of Mediterranean descent.
Alpha Thalassemia
◦ Alpha thalassemia is usually due to the deletion of at least
one of the four existing alleles.

◦ In a normal cell, the α-globin chains are coded by a total of

four alleles. Thus, there are four forms of the disease. The
severity of alpha thalassemia depends on the number of
defective α-globin alleles.
Alpha Thalassemia
Type Mutated gene Clinical features
Silent carrier One defective allele (-α/αα) • Typically no anemia

Alpha thalassemmia trait Two defective alleles (-α/-α or --/αα) • No or mild anemia

Hemoglobin H disease Three defective alleles (--/-α) • Jaundice and anemia at birth.
• Chronic hemolytic anemia (that may
require transfusions)
• Secondary hemochromatosis
• Hepatosplenomegaly

Hemoglobin Bart's disease Four defective alleles (--/-‑) • Hydrops fetalis

Consists of four γ-chains (γ- • Intrauterine ascites
tetramers)
β-Thalassemia
• In a normal cell, the β-globin chains are coded by a
total of two alleles. Thus, there are two main
forms of the disease.
• Beta-thalassemia minor (trait): one defective allele
• Beta-thalassemia major : two defective alleles.
Clinical Manifestations
• Pallor
• Jaundice
• Bossing of the skull
• Maxillary overgrowth
• Splenomegaly
• Hepatomegaly
Investigations
• CBC
• microcytic hypochromic anemia
• Normal RDW
• Liver chemistries: hyperbilirubinemia (indirect)
• Iron studies (particularly ferritin) : expected to be normal in thalassemia
• Peripheral blood smear findings include:
• Target cells
• HbH inclusion bodies
• Teardrop cells
• Hb-electrophoresis.
Management
All patients: Patient education, genetic counseling, and screening tests for relatives.
Thalassemia minor
Usually, no treatment is required.
Episodic folic acid supplementation may be indicated (e.g acute infections)
Thalassemia major and intermedia
Transfusion therapy (erythrocyte concentrates)
• Indication (for transfusion-dependent thalassemias): Hb < 7 g/dL or marked clinical symptoms
• Target: Hb > 9–10 g/dL
Surveillance and treatment of complications.
Iron overload diseases: chelating agents, e.g., deferasirox, indicated when iron accumulation reaches
toxic levels.
Select patients
Splenectomy
Stem cell transplantation.
Glucose-6-Phosphate Dehydrogenase (G6PD)
deficiency
• X-linked recessive inheritance
• G6PD is the rate-limiting enzyme of the pentose phosphate pathway. This pathway yields NADPH, which is
essential for converting oxidized glutathione back to its reduced form. Reduced glutathione is capable of
neutralizing reactive oxygen species (ROS) and free radicals and therefore protecting RBCs from oxidative damage.
• In the absence of reduced glutathione (e.g., due to G6PD deficiency), RBCs become susceptible to oxidative stress
that can damage erythrocyte membranes, resulting in intravascular and extravascular hemolysis.
Hemolytic Crisis
Causes of increased oxidative stress are triggers of hemolytic crisis and include:
• Fava beans
• Drugs: antimalarial drugs (e.g., chloroquine, primaquine), sulfa drugs (e.g., trimethoprim-
sulfamethoxazole), nitrofurantoin, isoniazid, dapsone, NSAIDs, ciprofloxacin.
• Bacterial and viral infections (most common cause): Severe enzymatic deficiency can inhibit respiratory
burst activity due to reduced NADPH production in phagocytes.
• Inflammation: During an inflammatory reaction free radicals are produced and can diffuse into RBCs.
• Metabolic acidosis
Recurring hemolytic crises may occur, especially following triggers
• Arise within 2–3 days after increased oxidative stress .
• Sudden onset of back or abdominal pain
• Jaundice
• Dark urine
• Transient splenomegaly
Investigations
• Blood smear: Heinz bodies and Bite cells.
• Screening test: fluorescent spot test: Add glucose-6-phosphate and NADP → measure NADPH
fluorescence .Normal G6PD activity produces fluorescent NADPH out of NADP, while in G6PD deficiency a lack of
fluorescence is seen.
• Confirmatory test: quantitative G6PD enzyme analysis: Ideally, both the screening and confirmatory tests should be
performed during remission.
Management
• Avoid precipitating factors, well
hydration.
• Transfusions rarely required even in
crisis.
Hereditary spherocytosis (HS)
Hereditary spherocytosis (HS) is the
most common congenital
hemolytic disorder among
individuals of northern European
descent. In most cases, it is an
autosomal dominant disease that is
caused by red blood cell (RBC)
membrane protein defects, which
render the RBCs more vulnerable to
osmotic stress and hemolysis.
Clinical Features
• Anemia and pallor.
• Jaundice (due to ↑ unconjugated bilirubin).
• Splenomegaly with left upper quadrant pain.
• Black pigment gallstones (made of calcium bilirubinate), may lead to
cholecystitis.
Investigations
• Laboratory findings
• Normocytic anemia: mean cell volume (MCV) within normal range or slightly
decreased.
• Increased mean corpuscular hemoglobin concentration (MCHC) ↑ Red blood
cell distribution width (↑ RDW)
• Blood smear: Characteristic spherocytes (small round cells without central pallor)
• Eosin-5-maleimide binding test (EMA binding test): Test of choice, as results are
readily available (within two hours) .Decreased binding between dye (eosin-5-
maleimide) and RBC membrane proteins. Binding is quantified using flow
cytometry, which shows decreased mean fluorescence spherocytes
Treatment
• Non-surgical treatments
• Phototherapy and/or exchange transfusions may be necessary in
neonates (e.g., to avoid kernicterus).
• Blood transfusions may be required in cases of aplastic or hemolytic
crisis.
• Folic acid supplementation to maintain erythropoiesis
• Splenectomy
• Sole definitive treatment
Iron deficiency anemia
• Iron deficiency refers to a state in which there is insufficient total body
iron to maintain normal physiologic functions.
• iron deficiency anemia (IDA) in children can be defined as:
• For children 6 months to <5 years: Ferritin <15 micrograms/L and
Hemoglobin <11 g/dL
• For children 5 to <12 years: Ferritin <15 micrograms/L and Hemoglobin
<11.5 g/dL.
Etiologies of iron deficiency anemia
• Iron losses
• Hookworm infestation.
• Hemorrhagic tendency (e.g., hemophilia).
• Decreased iron intake
• Chronic undernutrition.
• Exclusive intake of nonfortified cow's milk.
• Exclusive breastfeeding after 6 months of age.
• Inflammatory bowel disease, celiac disease.
• Increased demand
• Growth
Clinical features of iron deficiency anemia
• Signs and symptoms of anemia (Fatigue, lethargy) Pallor
(primarily seen in highly vascularized mucosa, e.g., the
conjunctiva), Cardiac: tachycardia, and dyspnea on exertion.
• Brittle nails, koilonychia (spoon-like nail deformity) , hair loss
• Pica.
• Angular stomatitis.
• Atrophic glossitis.
• IDA can be associated with Plummer-Vinson syndrome
(PVS).
Investigations
• Red blood cell indices
• Mean corpuscular volume: Typically ↓ (microcytic)
• Mean corpuscular hemoglobin: Typically ↓ (hypochromic)
• Normal or ↓ reticulocyte count
• Red cell distribution width (RDW) : Increases in established IDA. Can help distinguish IDA from anemia of
chronic disease and certain types of thalassemia (in which the RDW is usually normal).
• iron studies
• Best initial test: ↓ serum ferritin ↓ Serum iron ↑ Serum transferrin and total iron binding capacity (TIBC)
↓Transferrin saturation (TSAT).
• Bone marrow biopsy
• Gold standard, but only indicated in patients with suspected IDA and equivocal iron studies.
• Findings: decreased or absent stainable iron stores.
Management
• Dietary modifications
• Encourage the consumption of iron-rich foods.
• Infants < 1-year-old: Avoid cow's milk.

• Iron therapy
• Oral iron therapy
• For infants and children with proven or suspected IDA: oral ferrous sulfate, 3 mg/kg
elemental iron, administered once daily
• Iron should be given in the morning or between meals and with water or juice
• The Hb will increase by about 1 g/dl per week
• The course of treatment: Minimum 3 months
• Parenteral iron therapy: considered second-line therapy for the majority of patients with (IDA)
Question 1
A 32-year-old woman from Vietnam, gives birth at 34 weeks’ gestation to a markedly hydropic
stillborn male infant. Autopsy findings include hepatosplenomegaly and cardiomegaly, serous
effusions in all body cavities, and generalized hydrops. No congenital anomalies are noted.
There is marked extramedullary hematopoiesis in visceral organs. Which of the following
hemoglobins is most likely predominant on hemoglobin electrophoresis of the fetal RBCs?
A.Hemoglobin A1
B.Hemoglobin A2
C.Hemoglobin Bart’s
D.Hemoglobin E
E.Hemoglobin F
F.Hemoglobin H
Question 2
A male infant was found to be jaundiced 12 hours after birth. At 36 hours of
age, his serum bilirubin was 18 mg/dL, hemoglobin concentration was 12.5
g/dL, and reticulocyte count 9%. Many nucleated RBCs and some spherocytes
were seen in the peripheral blood smear. The differential diagnosis should
include which of the following?
a. Pyruvate kinase deficiency
b. Hereditary spherocytosis
c. Sickle-cell anemia
d. Rh incompatibility
e. Polycythemia
Question 3
A 4-year-old previously well African American boy is brought to the office by his aunt. She reports
that he developed pallor, dark urine, and jaundice over the past few days. He stays with her, has not
traveled, and has not been exposed to a jaundiced person, but he is taking trimethoprim
sulfamethoxazole for otitis media. The CBC in the office shows a low hemoglobin and hematocrit,
while his “stat” serum electrolytes, blood urea nitrogen (BUN), and chemistries are remarkable only
for an elevation of his bilirubin levels. His aunt seems to recall his 8-year-old brother having had an
“allergic reaction” to aspirin, which also caused a short-lived period of anemia and jaundice. Which
of the following is the most likely cause of this patient’s symptoms?
a. Hepatitis B
b. Hepatitis A
c. Hemolytic-uremic syndrome
d. Gilbert syndrome
e. Glucose-6-phosphate dehydrogenase deficiency
References
• https://next.amboss.com/us/article/pT0L72?q=iron+deficiency+anemia
• https://next.amboss.com/us/article/gn0Fsg#Za618edd4a5927604448cdc7
0d4c16172
• https://next.amboss.com/us/article/7T04H2?q=hereditary+spherocytosis
• Paediatric Pre-test
Thank You
Questions?