HEMATOLOGICAL DISORDERS
Hematopoiesis
 It is the process, which maintains lifelong production of
hematopoietic blood cells.
 The main site of hematopoiesis:
o In fetal life: the liver
o Throughout postnatal life: the bone marrow
 All hematopoietic cells are derived from pluripotent
hematopoietic stem cells
Erythropoiesis
Erythropoiesis begins with stem cell called hemocytoblast, which is
then converted to proerythroblast. Development and differentiation
to stage of reticulocyte takes 4-5 days. Then erythrocyte achieves its
mature form in 45-70 hours in blood
Characteristics of erythrocytes
• Diameter: 7,5 micrometer
• No nucleus
• Biconcave disk
• 95% of its mass is hemoglobin
• Physical properties: soft, flexible, elastic
Fetal Hemoglobin
Fetal hemoglobin has a higher affinity for oxygen – necessary for
relatively hypoxic environment of the fetus.
Hematological values at birth and the first few weeks of life
• At birth, the Hb in term infants is high, 14-21.5g/dl, to
compensate for the low oxygen concentration in the fetus.
• The Hb falls over the first few weeks, due to reduced
erythropoiesis, reaching a nadir of 10 g/dl at 2 months of age
• Preterm babies have a steeper fall in Hb to 6.5-9 g/dl at 4-8 weeks
of age.
• Normal blood volume at birth: 80 ml/kg; in preterm infants 100
ml/kg.
• White blood cell counts in neonates are higher than in older
children (10-25 × 109/L).
• Platelet counts at birth – as in adults (150-400 × 109/L).
Anemia
• Anemia is defined as a decrease of hemoglobin (Hb) level below
the normal range for a child of that age and gender.
• The normal range varies with age, so that normal values in
pediatrics must be correlated with the patient’s age.
Anemia can be defined:
• Neonate: Hb <14 g/dl
• 1-12 months: Hb <10 g/dl
• 1-12 years: Hb <11 g/dl.
Mechanism
The type of anemia defines its pathophysiologic mechanism and its
essential nature, allowing for appropriate therapy.
• Impaired/reduced red cell production - either due to ineffective
erythropoiesis (e.g. iron deficiency) or due to red cell aplasia
• Increased red cell destruction (excessive hemolysis)
• Blood loss - relatively uncommon cause in children unless
traumatic
• Blood loss should be the first consideration. Once it is ruled out,
only the other two mechanisms need to be considered.
• RBC survival is 120 days - maintenance of RBC population
requires daily renewal of 1/120 of the cells.
• Complete cessation of erythropoiesis results in a decline of about
10%/wk (1%/day) of RBCs. When RBC values fall >10%/wk
without blood loss, hemolysis is a causative factor.
Classification according to the Blood Film
• Microcytic: Red blood cells have a low mean cell volume
(MCV), appear small and pale
• Macrocytic: A large MCV, appear large and oval shaped
• Normocytic: Red blood cells may be normal in size and shape
but may be reduced in number
Microcytosis
Anything that impairs hemoglobin production
(Deficient or defective heme or globin synthesis)
Clinical manifestation:
- The clinical manifestations vary with the age, degree and
rapidity of onset, presence of subjacent illness and other
factors.
- Mild anemia is often asymptomatic (until Hb below 6-7 g/dL)
- The main consequence of anemia is tissue hypoxia. If anemia
has developed rapidly, there may not be adequate time for
compensatory adjustments to take place, so there is a sudden
marked contraction of intravascular volume, resulting in
postural hypotension, fall in cardiac output, shunting of blood
from skin to central organs, sweating, restlessness, thirst and
air hunger.
- If anemia has slowly installation, many adaptations for the
oxygen maintenance occur, such as an increase of plasmatic
volume and right shift of the oxygen-hemoglobin dissociation
curve.
Symptoms:
- Pallor (color of skin, palms, oral and conjunctival mucous
membrane and nail beds)
- Fatigue
- Apathy
- Dyspnea
- Anorexia
- Headache
- Pica (consumption of non-food substances such as ice, chalk,
ashes or clay, frequently found in iron deficiency anemia)
- Bowel disturbance
- Tachycardia
- Syncope (particularly following exercise)
- Wide pulse pressure, bounding pulse.
- Headache
- Syncope
- Tinnitus or vertigo
- Irritability
Complication:
 Pediatric anemia may result in life-long deficits:
o Negative effects persist despite correction of anemia
 Motor Effects:
o Decreased gross and fine motor coordination
 Cognitive effects:
o Lower scores on intelligence testing
o Long-term functional impairment in school
 Behavioral effects:
o Fearfulness and unhappiness
o Early fatigue, less playful, clingy
Physical Examination:
Physical findings can include:
o Jaundice
o Splenic enlargement
o Neurologic symptoms (loss of vibration sensibility,
abnormal march)
o Tongue atrophy
o Lymphadenopathy
o Evidence of blood in feces or vomit
o Petechiae
o Myriad signs of primary diseases that may cause a
secondary anemia
Laboratory Findings:
o Complete blood count (with reticulocyte count, platelet
count, mean cellular volume-VCM- and differential
leukocyte count).
o Peripheral blood smear can confirm size and color of RBC,
particularly important in evaluating a patient with
hemolysis.
o Serum ferritin level, serum iron, and total iron binding
capability (TIBC).
o Bone marrow aspiration is useful and critical in the workup
of any unexplained anemia, especially in underproduction
anemia.
Acute Post-hemorrhagic anemia
o Because marrow reserve is limited, anemia may result from
massive hemorrhage associated with spontaneous or
traumatic rupture or incision of a large blood vessel, erosion
of an artery by lesions (e.g., peptic ulcer, neoplasm), or
failure of normal hemostasis.
o Immediate effects depend on the duration and volume of
hemorrhage. Sudden loss of 1/3 of blood volume may be
fatal, but as much as 2/3 may be lost slowly over 24 h
without such a risk.
o Symptoms are caused by a sudden decrease in blood volume
(hypovolemic shock) and by subsequent hemodilution with
a decrease in the oxygen-carrying capacity of the blood.
Symptoms and Signs
o Faintness
o Dizziness
o Thirst
o Sweating
o Weak and rapid pulse
o Rapid respiration (at first deep, then shallow)
o Orthostatic hypotension is common.
o Blood pressure may at first rise slightly, because of reflexive
arteriolar constriction, and then it gradually falls.
o If bleeding continues, blood pressure may fall and death may
ensue
Laboratory Findings
During and immediately after hemorrhage, the RBC count, Hb, and
Hct may be deceptively high because of vasoconstriction.
Within a few hours, tissue fluid enters the circulation, resulting in
hemodilution and a drop in the RBC count and Hb proportional to the
severity of bleeding.
The resultant anemia is normocytic.
Polymorphonuclear granulocytosis and a rise in platelet count may
occur within the first few hours.
Several days after the bleeding event, regeneration (ie,
reticulocytosis) is evident: Blood smears may disclose
polychromatophilia and slight macrocytosis.
If hemorrhage was massive and acute, occasional normoblasts and
immature WBCs may be seen.
Abnormal RBC production
 Microcytic anemia:
o Iron deficiency
o Thalassemia
o Sideroblastic anemia
 Macrocytic anemia (megaloblastic):
o Folate and vitamin B12deficiency
 Normocytic anemia:
o Aplastic and Hypoplastic Anemia
o Anemia of chronic disease
Anemia – Reduced RBC production
Etiology:
'Ineffective erythropoiesis'- red cell production occurs at a normal or
increased rate but differentiation or survival of the red cells is
defective (e.g. iron deficiency).
Complete absence of red cell production (red cell aplasia).
Diagnostic clues to ineffective erythropoiesis are:
 Normal reticulocyte count
 Abnormal mean cell volume (MCV) of the red cells:
o Low in iron deficiency and high in folic acid deficiency or
myelodysplasia.
Iron Deficiency Anemia – Etiology:
I. Inadequate intake - dietary (milk)
II. Increased demand:
Low birth weight
Prematurity
Low birth weight
Multiple births
High growth rate
Adolescence
Pregnancy
III. Blood loss
 Perinatal
o Placental
 Trans-placental bleeding into maternal circulation
 Intra-placental
 Fetal blood loss at or before birth
 Fetofetal
o Umbilicus
 Ruptured umbilical cord
 Inadequate cord tying
 Post-exchange transfusion
 Postnatal:
o Gut:
o Primary anemia resulting in gut alteration with blood
loss aggravates existing iron deficiency
o Hypersensitivity to cow milk protein; exudative
enteropathy
o Anatomic gut lesions – varices, hiatus hernia, ulcer, ileitis
Meckel’s diverticilum, hereditary teleangiectasia,
o Gastritis (from aspirin ingestion, adenocortical steroids)
o Henoch – Schonlein purpura
o Nose: recurrent epistaxis
o Uterus: menstrual loss
o Kidney:
 Hematuria,
 Nephrotic syndrome (urinary loss of transferrin)
 Noctural Hemoglobinuria
o Hemodialysis
o Trauma
IV. Impaired absorption:
• Malabsorption syndrome
• Celiac disease
• Severe prolonged diarrhea
• Inflammatory bowel diseases
• Short bowel syndrome
Iron Deficiency Anemia – Risk Factors
 Early cow’s milk intake
 Late solid food intake
 Frequent tea intake (tannin inhibits absorption)
 Low vitamin C intake
 Low meat intake
 Breast-feeding for more than 6 months without iron-reach foods
or supplements
 Low socioeconomic status (frequent infections)
Iron Deficiency Anemia – Blood Count
 Hemoglobin is below the lower limit of normal for age
 The reticulocyte count is usually normal
 Thrombocytopenia is more common in severe iron-deficiency
anemia
 Thrombocytosis is present, when there is associated bleeding
from the gut
 Low serum ferritin
 Serum iron and iron binding capacity:
- Decreased serum iron
- Increased iron binding capacity
Iron Deficiency – Tissue Effect
I. Gastrointestinal tract
 Anorexia common and early
o Increased proportion of low-weight percentiles
o Depression of growth
 Atrophic Glossitis
 Dysphagia
 Reduced gastric acidity
 Leaky gut syndrome
o Guaiac-positive stools
o Exudative eneropathy: gastrointestinal loss of protein,
albumin immuno-globulins , copper , calcium, red cells
 Malabsorption syndrome
o Iron only
o Generalized Malabsorption: Xylose, Fat, Vitamin A,
Duodeno-jejunal mucosal atrophy
II. Central nervous system
• Irritability
• Fatigue
• Conduct disorders
• Lower mental and motor development
• Papilledema
III. Cardiovascular system
 Increase heart rate and cardiac output
 Cardiac hypertrophy
 Increase in plasma volume
 Increased minute ventilations values
 Immunologic system: There is conflicting information as to the
effect on the immunologic system of iron-deficiency anemia
 Evidence of increased predisposition to infections
o Reduction of acute illness in iron-deficient children by iron
treatment and improved rate of recovery
o Increased frequency of respiratory infection in iron
deficiency
o Impaired leukocyte transformation
o Impaired granulocyte killing
 Evidence of decreased predisposition to infections
o Lower frequency of bacterial infection in iron-deficient
children
Macrocystic (Megablastic) Anemia
 Megaloblastic anemia may result from deficiencies of Folate or
B12vitamin.
 This deficiencies lead to impairment of DNA synthesis in rapidly
growing tissue and in consequence to disproportionate
maturation in the cytoplasm and nucleus during erythropoiesis.
 Vitamin B12 deficiency occur very rare in children
 Folate deficiency can occur as a result of inflammatory bowel
disease, celiac disease, anticonvulsant therapy
 Bone marrow (ineffective erythropoiesis)
Normocytic Anemia
• Primary bone marrow disorders (aplasia and hypoplasia,
myelodisplasia, myelofibrose, hematologic and solid tumors, HIV
infection, granulomas)
• Chronic disease anemia
• Secondary anemia (hepatic, renal or endocrine disorders)
Aplastic and Hypoplastic Anemia
 Anemia resulting from a loss of RBC precursors, either from a
defect in stem cell pool or an injury to the microenvironment that
supports the marrow, and often with borderline high MCV values.
 The term aplastic anemia (bone marrow failure) commonly
implies a panhypoplasia of the marrow with associated
leukopenia and thrombocytopenia.
 The term pure RBC aplasia, defines the selective marked
reduction or absence of erythroid precursors.
 Although both disorders are uncommon, aplastic anemia is more
common.
 Both, aplastic and Hypoplastic Anemia may be acquired or
congenital
Acquired Aplastic Anemia
Etiology and pathogenesis:
About 1/2 of the cases of true aplastic anemia are idiopathic.
Recognized causes are:
o Chemicals (e.g. benzene, inorganic arsenic),
o Radiation
o Drugs (e.g. antineoplastic, antibiotics, NSAIDs, anticonvulsants)
Symptoms and signs:
• Signs vary with the severity of the pancytopenia.
• General symptoms of anemia are usually severe.
• Waxy pallor of skin and mucous membranes. Chronic cases may
show considerable brown skin pigmentation.
• Severe thrombocytopenia, with bruising and bleeding.
Hemorrhages into the ocular fundi are frequent.
• Agranulocytosis with life-threatening infections.
• Splenomegaly is absent, unless induced by transfusion
hemosiderosis.
Laboratory findings:
• RBCs are normochromic-normocytic (sometimes marginally
macrocytic).
• A WBC count <= 1500/µL3 is common, the reduction occurring
chiefly in the granulocytes.
• Platelets are often markedly reduced.
• Reticulocytes are decreased or absent, even with coexistent
hemolysis.
• The aspirated bone marrow is acellular.
• Serum Fe is elevated.
Congenital Aplastic Anemia
Fanconi´s Aniemia
A very rare congenital form of aplastic anemia (autosomal recessive)
Presents at 5-6 years of age. Transforms into acute leukemia.
Symptoms:
o Bone abnormalities (radius, thumbs)
o Short stature
o Renal malformations
o Microcephaly
o Hypogonadism, and
o Brown pigmentation of skin
Schwachman-Diamond Syndrome
A rare congenital condition (autosomal recessive)
Mild pancytopenia or isolated neutropenia
Transforms to acute leukemia.
Symptoms:
o Bone marrow failure
o Pancreatic exocrine failure
o Skeletal abnormalities
Red cell aplasia (Hypoplastic Anemia)
Etiology:
o Congenital red cell aplasia (Diamond-Blackfan anemia)
o Transient erythroblastopenia of childhood
o Parvovirus B19 infection - only causes red cell aplasia in children
with inherited hemolytic anemia’s and not in healthy children.
Diagnostic Clues:
• Low reticulocyte count despite low Hb
• Normal bilirubin
• Negative direct antiglobulin test (Coombs' test)
• Absent red cell precursors on bone marrow examination
Blackfan – diamond anemia
o A rare congenital disease
o 80% Sporadic mutation
o Presentation at 2-3 months, 25% at birth
o Short stature and abnormalities of the thumbs or digits
o RBC may have fetal Hb.
o Treatment with steroids (60-70% responders) or monthly RBC
transfusions
Transient erythroblastopenia of childhood (TEC)
A brief reversible disappearance of RBC precursors in the marrow
during various acute viral illnesses in young children. TEC is thought
to be due to an abnormal response to infection, perhaps via an
antibody that inhibits RBC progenitors. The RBC are normal in size
and do not express fetal characteristics.
Parvovirus B19 infection
o Only in children with chronic hemolytic anemia, parvovirus B19
infection may cause aplastic crises (direct infection of the RBC
progenitors)
o Usually last 1-2 weeks, but prolonged aplasia has been described.
Increased red cell destructions hemolytic - Anemia
• The essential feature of hemolytic anemia is a reduced RBC
lifespan (normal - about 120 days), due to increased red cell
destructions in the circulation (intravascular hemolysis) or liver
or spleen (extravascular hemolysis)
• Hemolysis results in anemia when bone marrow production can
no longer compensate for the shortened RBC survival (eightfold
increase possible)
Etiology:
 Immune hemolytic anemia – common in neonates, uncommon in
elder children
 The main cause of hemolysis in children is intrinsic abnormalities
of the red blood cells:
o Red cell membrane disorders (e.g. hereditary
spherocytosis)
o Red cell enzyme disorders (e.g. glucose-6-phosphate
dehydrogenase deficiency)
o Hemoglobinopathies (abnormal hemoglobin, e.g. βthalassemia major, sickle cell disease).
Increased red cell breakdown lead to:
 Anemia
 Reticuloendothelial hyperplasia - hepatomegaly and
splenomegaly
 Elevated unconjugated bilirubin
 Excess urinary urobilinogen.
Diagnosis
 Raised reticulocyte count (on the blood film this is called
'polychromasia' as the reticulocytes have a characteristic lilac
color)
 Unconjugated bilirubinaemia and increased urinary urobilinogen
 Abnormal appearance of the red cells on a blood film (e.g.
spherocytes, sickle shaped or very hypochromic)
 Positive direct antiglobulin test – Coombs’ test identifies antibodycoated red blood cells (positive only if an immune cause of
hemolytic anemia)
 Increased erythropoiesis in the bone marrow.
Hereditary spherocytosis
• 1 in 5000 births in Caucasians
• An autosomal dominant inheritance, 25% caused by new
mutations
• Mutations in genes for the skeletal proteins of the red cell
membrane (mainly spectrin, ankyrin or band 3).
• Reduction in red cells surface-to-volume ratio causes the cells to
become spheroidal
• RBC are less deformable – what leads to their destruction in the
microvasculature of the spleen.
Symptoms:
 Jaundice - usually develops during childhood but may be
intermittent; (may cause severe hemolytic jaundice in the first few
days of life)
 Anemia - mild anemia (hemoglobin 9-11g/dl)
- The hemoglobin level may fall with an intercurrent infection
- Many children have 'compensated' hemolysis with a normal
hemoglobin
 Mild to moderate splenomegaly - depends on the rate of
haemolysis;
o This may be the mode of presentation in the first year of life
 Aplastic crisis - uncommon, associated with parvovirus B19
infection
 Gallstones - due to increased bilirubin excretion.
Diagnosis:
• The blood film usually diagnostic
• Specific tests available (e.g. osmotic fragility)
Differential diagnosis:
Antibody-induced anemia may be associated with spherocytosis. It
must be excluded with a direct antiglobulin test especially in the
absence of a family history.
Glucose -6 – phosphate dehydrogenase (G6PD) deficiency
• The most common red cell enzymopathy
• Over 100 million people are affected
• High prevalence (10-20%) in central Africa, the Mediterranean,
the Middle East and the Far East.
• Many different mutations - different clinical features
• G6PD is essential for preventing oxidative damage to red cells.
Red cells lacking G6PD are susceptible to oxidant-induced
haemolysis.
• X-linked inheritance – males predominantly affected (10-15%
normal enzyme activity)
• Females - heterozygotes – 50% of the normal G6PD activity.
Symptoms:
o Neonatal jaundice: In the first 3 days of life - it is the most common
cause of severe neonatal jaundice requiring exchange transfusion.
o Acute haemolysis - precipitated by:
o Infection, the most common precipitating factor
o Certain drugs (antimalarials, sulphonamides, quinolones,
high dose aspirin)
o Fava beans (broad beans)
o Naphthalene in mothballs
Diagnosis:
o Measuring G6PD activity in red blood cells
o Misleadingly elevated enzyme level during hemolytic crisis –
Young red blood cells may have normal enzyme activity whilst
older cells are deficient - a need for repeated assay
Hemoglobinopathies
Red blood cell disorders which cause hemolytic anemia because of:
 Reduced or absent production of HbA (α- and β-thalassemia) or
 Production of an abnormal Hb (e.g. sickle cell disease).
 α-Thalassemia are caused by deletions in the α-globin gene.
 β-Thalassemia and sickle cell disease are caused by mutations of
the β-globin gene. Clinical manifestations of the
Hemoglobinopathies affecting the β-chain are delayed until after 6
months of age when most of the HbF present at birth has been
replaced by adult HbA
Sickle cell disease
 The most common genetic disorder in children in many European
countries, (prevalence 1 in 2000 live births) - neonatal screening
using the biochemical screening test (Guthrie test)
 Hemoglobinopathies in which HbS is inherited. HbS forms as a
result of a point mutation in codon 6 of the β-globin gene
 Most common in patients from tropical Africa or the Caribbean, is
also found in the Middle East and in low prevalence in most other
parts of the world except for northern Europeans
Pathogenesis:
 HbS molecule becomes deformed (insoluble) in the deoxygenated
state. HbS polymerises within red blood cells forming rigid
tubular spiral bodies, which deform the red cells into a sickle
shape.
 Irreversibly sickled red cells have a reduced lifespan and may be
trapped in the microcirculation, resulting in thrombosis and
therefore ischemia in an organ or bone.
 This is exacerbated by low oxygen tension, dehydration, cold,
excessive exercise or stress.
 The clinical manifestations vary widely between different
individuals.
Symptoms
o Anemia (6-8 g/dl)with jaundice
o Infection (pneumococcal or H. influenza) due to hyposplenism
secondary to micro-infarction in the spleen)
o Painful vaso-occlusive crisis: in any organ (hand-foot
syndrome with dactylitis), cerebral and pulmonary infarction
less common but serious (stroke)
o Acute anemia: Hemolytic, aplastic or sequestration crises
from accumulation of sickled cells in spleen
o Priapism
o Splenomegaly
o Long term problems: cognitive problems, heart failure, cardiac
enlargement, renal dysfunction, gallstones, leg ulcers, short
stature and delayed puberty
B-Thalassemia
 In people from the Indian subcontinent, Mediterranean and
Middle East
 As there is a deficiency of β-chains, γ-chain synthesis continues
beyond the neonatal period, producing an increased proportion of
HbF, and δ-chain production increases the amount of HbA2. This
results in precipitation of globin chains within the red cell
membrane, bringing about cell death within the bone marrow
(ineffective erythropoiesis) and premature removal of circulating
red cells by the spleen.
 The disease severity of β-thalassaemia depends on the amount of
HbA and HbF present:
o β-Thalassemia major - HbA (α2β2) cannot be produced
because of the abnormal β-globin gene. The most severe
form.
o β-Thalassemia intermedia - the β-globin mutations allow a
small amount of HbA and/or a large amount of HbF to be
produced. Milder, variable.
o β-Thalassemia trait - one normal and one abnormal β-globin
gene. Asymptomatic carrier
Symptoms:
 Severe anemia and jaundice from 3-6 months of age
 Failure to thrive/growth failure
 Extra-medullary hematopoiesis, causing bone marrow expansion
(classical feces with maxillary overgrowth and skull bossing)
 Marked hepatosplenomegaly (not seen in appropriately
transfused children).
Blood Transfusion
 RBC lifelong monthly transfusions
 The complications of multiple transfusions:
o Chronic iron overload: causes cardiac failure, liver cirrhosis,
diabetes, infertility and growth failure - iron chelation
therapy with subcutaneous desferrioxamine, given
overnight from 2 to 3 years of age
o Allo-antibody formation – problems with compatible blood
o Infections (HIV, Hepatitis A, B, C, malaria – rare)
o Problems with venous access
 Bone marrow transplantation if possible
 Healthy individuals have four α-globin genes. The manifestation of
α-thalassemia syndromes depends on the number of functional αglobin genes.
 α-thalassemia major (Hb Barts hydrops fetalis) - deletion of all
four α-globin genes, so no HbA (α2β2) can be produced. It
presents in mid-trimester with fetal hydrops (edema and ascites)
from fetal anaemia, which is always fatal in utero or within hours
of delivery.
 When only three of the α-globin genes are deleted (HbH disease),
affected children have mild-moderate anemia
Anemia in neonates
Symptoms:
 Pallor
 Air hunger
 Hypotension or shock
 In extreme cases, heart failure and hydrops may develop
Etiology:
 Prenatal factors:
o Placenta praevia
o Cord rupture
o Feto-maternal or feto-placental bleeding
o Twin-twin transfusion
 Postnatally:
o Hemorrhage in the neonate, for example as a result of
trauma or coagulopathy
o Iatrogenesis - phlebotomy in sick neonates, lab test
 Increased breakdown may be the result of:
o Hemolytic disease of the newborn
Hemolytic disease of the newborn:
 Hemolytic disease of the newborn is diagnosed when hemolysis of
a neonate's red blood cells is caused by antibody from the mother.
 This condition only occurs where there is incompatibility between
the maternal and fetal blood.
Etiology:
o One of the most severe causes of this condition is rhesus (Rh)
incompatibility.
o Other causes include, in descending order of frequency and
severity:
- AB0 system incompatibility
- Red blood cell metabolic disorders
- G-6-PD (glucose-6-phosphate dehydrogenase)
deficiency
- Pyruvate kinase deficiency
- RBC morphology disorders - for example, hereditary
spherocytosis,
o Hereditary elliptocytosis
o Rhesus incompatibility tends to be more severe than AB0
incompatibility because anti-D antibodies are mainly IgG, which
can easily cross the placenta, whereas anti-A and anti-B antibodies
are mainly IgM, which cannot cross the placenta.
Investigation
If hemolytic disease of the newborn is suspected, the following
investigations should be carried out:
o Full blood count, with attention to hemoglobin, white cells and
reticulocytes
o Platelets
o Infant blood group and Coombs test
o Maternal blood group and hemolysis
o Red cell enzyme assay may be a helpful second line investigation
o Blood film and osmolar fragility may diagnose spherocytosis