hematological changes and Hematological diseases in neonates

Done by dr. Zobeda Khalaf
Supervisor dr Samer Salh
Neonatal Hematology and
Hemorrhagic Diseases of
Newborn

Introduction
• Newborns are at risk of bleeding disorders due to
immature liver function, vitamin K deficiency, or
inherited coagulation disorders.
• Early recognition is essential to prevent life-
threatening hemorrhage.

Objectives
• Identify common causes of neonatal bleeding.
• Understand the pathophysiology of vitamin K
deficiency bleeding (VKDB).
• Recognize hemophilia, thrombocytopenia, and
platelet function disorders in neonates.
• Describe diagnostic evaluation and preventive
strategies.

• Neonatal hematologic disorders may be physiologic or pathologic.
1. Physiologic Hematologic Changes
These are normal, expected changes in neonates:
• Physiologic anemia of the newborn:
◦ After birth, hemoglobin drops naturally as fetal RBCs are replaced by adult-type
RBCs.
◦ Usually mild and self-limited.
• Leukocytosis at birth:
◦ A transient increase in WBCs due to stress of delivery.
• Polycythemia:
◦ Mild increase in hematocrit can be normal, especially in term or delayed cord
clamping.

2. Pathologic Hematologic Disorders
These indicate underlying disease or abnormality:
• Anemia: From blood loss, hemolysis (e.g., Rh or ABO incompatibility),
or marrow failure.
• Thrombocytopenia: Due to infection, maternal alloimmunization, or
congenital syndromes.
• Coagulation defects: Vitamin K deficiency, hemophilia, or DIC.
• Leukopenia / neutropenia: Can signal congenital immunodeficiency or
sepsis.

Placental Transfusion at Birth
Placental blood volume: ~75–125 mL
Rapid transfer: About 1/4 of this volume is transfused to the newborn within the first 15
seconds after birth
.
Importance:-
.Provides extra RBCs, iron, and stem cells to the newborn
.Helps improve hemoglobin levels and iron stores in the first months of life
:Clinical practice
.Delayed cord clamping (30–60 seconds or more) allows maximum placental transfusion
.Especially beneficial for preterm infants to reduce anemia and improve hemodynamics

“Delayed Cord Clamping and Neonatal Hematology”
can be defined
as:
The practice of
waiting for a
short period
(typically 1–3
minutes) after
birth before
clamping and
cutting the
umbilical cord.

de
fi
ned as a venous haematocrit over 0.65 and can
occur with twin–twin transfusion, intrauterine growth
restric-
tion and maternal hypertension or diabetes. If
symptoms are
present, it should be treated with partial exchange
transfusion
using a crystalloid solution.
Neonatal polycythaemia

Physiologic Anemia of the Newborn
• Term infants: Hb ≈ 11.4 ± 0.9 g/dL
• Preterm infants: Hb ≈ 7–10 g/dL
• Cause: Normal postnatal decline in hemoglobin as fetal RBCs are replaced
by adult-type RBCs.
• Timing: Usually occurs at 6–12 weeks in term infants, earlier in preterms.
• Clinical significance: Usually mild and self-limiting, rarely requires
treatment.
(physiological anaemia of prematurity)

Hemorrhagic Disease of the Newborn (HDN)
• Cause: Deficiency of vitamin K-dependent clotting factors (I, II, VII,
IX, X).
• Pathophysiology:
◦ Vitamin K is required for carboxylation of gamma acid inin
◦
Of clotting factors.
◦ Without it → nonfunctional clotting factors → impaired coagulation.
• Clinical manifestation: Bleeding (skin, mucosa, GI tract, intracranial).
• Epidemiology: 0.25–1.7% in neonates without prophylaxis.
• Timing: Usually first 5 days to 6 weeks.
• Prevention: Vitamin K administration at birth restores normal
coagulation.

Hemolytic Disease of the Newborn (HDN)
1. Immune Causes
• Alloimmune:
◦ Maternal antibodies against fetal RBC antigens (e.g., Rh, ABO
incompatibility)
• Autoimmune:
◦ Rare; maternal autoantibodies cross placenta
2. Non-Immune Causes
• Membranopathies: e.g., Hereditary spherocytosis
• Enzymopathies: e.g., G6PD deficiency, pyruvate kinase deficiency
• Hemoglobinopathies: e.g., Sickle cell disease, thalassemia

Three Types of Alloimmune HDN
1. ABO Incompatibility
◦ Most common type.
◦ Mother: blood group O → baby: A or B.
◦ Usually mild hemolysis.
2. Rh Incompatibility
◦ Most severe type.
◦ Anti-D antibodies most common.
◦ Can be accompanied by other Rh antibodies: anti-C, -c, -E, -e.
3. Other Alloantibodies
◦ Unexpected immune antibodies other than anti-D.
◦ Examples: Jk, K, Fy, S.
◦ Usually less common but can cause significant hemolysis.

ABO Hemolytic Disease of the Newborn (HDN)
• Mother: Blood group O
• Baby: Blood group A or B
• Mechanism:
◦ Group O individuals have anti-A and anti-B antibodies
◦ Fetal RBCs are attacked → hemolysis
• Incidence & Severity:
◦ Occurs in ~3% of newborns
◦ Severe in ~1%
◦ <1:1,000 require exchange transfusion
Key point:
• Usually mild, but lab monitoring for anemia and jaundice is important.

“Other” Alloimmune HDN
• Uncommon (~0.8% of pregnancies)
• Causes: Maternal alloantibodies against fetal RBC antigens:
◦ Anti-E, -c, -Kell, -Kidd, -Duffy
• Anti-Kell (K) speci
fi
cs:
◦ Can range from mild to severe disease
◦ Over 50% of cases associated with multiple maternal transfusions
◦ Second most common cause of severe HDN after Rh disease

Rh Hemolytic Disease of the Newborn (HDN)
• Most common severe HDN: Anti-D antibodies
• Severity: Can range from mild to severe
• Other Rh antibodies:
◦ Anti-c: mild to severe; third most common severe HDN
• Epidemiology:
◦ Rare in China & Japan (Rh-negative genotype nearly absent)
• Pathogenesis / Risk Factors:
◦ Maternal exposure: 0.05–0.1 mL fetal blood can sensitize mother
◦ Increased risk with:
▪ Toxemia of pregnancy
▪ Manual removal of placenta
▪ Cesarean section
Key point:
• Maternal alloimmunization → fetal RBC destruction → anemia, jaundice, hydrops fetalis

Iatrogenic Anemia in Neonates
• Cause: Frequent blood sampling in NICU or hospital
• Blood loss: Can remove up to 20% of total blood volume
• Example:
◦ Infant weighing 1500 g → 25 mL blood loss → may cause
anemia
• Hidden loss: ~10% of blood loss may not be immediately
recognized
Key point:
• Iatrogenic anemia is preventable with careful monitoring and
minimizing unnecessary blood draws.

Pathophysiology of
neonatal anemia

High-Dead-Space Syringe Design
• Definition: Syringes where a significant
volume of liquid remains in the hub/
needle after injection.
• Problem: Newborns have very little blood.
• HDS syringes waste some blood or
medicine.
• This can cause anemia or underdosing.
• Solution: Use low-dead-space (LDS)
syringes.
• Reduces blood loss, especially in the NICU
where many small samples are taken.

Hemoglobinopathies in Neonates
• Predominant hemoglobin at birth: HbF (α₂γ₂)
• β-chain disorders (e.g., Sickle Cell Disease, β-thalassemia) usually do not cause
problems immediately.
• Reason: β-globin chains are not expressed much in newborns → symptoms appear
later.
Key point:
• Neonatal screening is important to detect hemoglobinopathies early, even before
symptoms develop.

G6PD Deficiency (Enzymopathy) in Neonates:
• Type: X-linked recessive inherited enzyme disorder
• Mechanism: RBCs break down under oxidative stress → hemolysis
• Clinical relevance: May cause neonatal jaundice and anemia
• Biochemistry:
◦ Deficiency of Glucose-6-Phosphate Dehydrogenase
◦ Impairs RBC protection against oxidative damage
Key point:
• Important cause of non-immune hemolytic anemia in newborns, especially in male infants.

Membranopathies
• Definition: Inherited disorders affecting the RBC membrane, making red cells fragile.
• Common types:
◦ Hereditary spherocytosis – spherical RBCs → destroyed in spleen
◦ Hereditary elliptocytosis – elliptical RBCs → mild hemolysis
• Clinical features:
◦ Hemolytic anemia
◦ Jaundice
◦ Splenomegaly (mainly in spherocytosis)
• Pathology focus:
◦ RBC shape abnormality
◦ Hemolysis due to mechanical fragility

Evaluation of Neonatal Anemia
. Site of Blood Sampling
• Capillary blood:
◦ Taken from heel or finger prick
◦ Small volume, convenient for routine screening
◦ May slightly overestimate hemoglobin compared to venous blood
• Venous blood:
◦ Taken from vein (e.g., antecubital or scalp vein)
◦ More accurate for complete blood counts and lab tests
◦ Requires skilled personnel, larger volume
Key point:
• Capillary sampling is often used for screening,
• Venous sampling is preferred for diagnosis and detailed evaluation.

Capillary vs Venous Blood Sampling in Neonates
Capillary blood may overestimate hemoglobin, so venous sampling is preferred for accurate
diagnosis, especially in preterm babies.
• Duplicate capillary sampling: Difference ~0.8 g/dL (capillary > venous)
• Maximum difference: Up to 3.6 g/dL
• Observed in both term and preterm infants
• Can persist up to 6 weeks – 3 months
• Most pronounced in premature infants

This image illustrates that
Capillary Hematocrit (from a
finger/heel stick) is consistently
higher than Venous Hematocrit
(from a vein) in the same person
This difference is important to
remember when interpreting
results, as a capillary sample
may overestimate the true red
blood cell count compared to the
gold-standard venous sample.

Leucocyte Disorder
Leukocyte (white blood cell) disorders in neonates can be divided into two main types:
1. Quantitative Disorders (Count Changes):
◦ These involve too many or too few white blood cells.
◦ Leukocytosis: WBC count higher than normal; can occur due to stress, infection, or inflammation.
◦ Leukopenia / Neutropenia: WBC count lower than normal; can be congenital, due to infection, or mat
factors.
◦ Clinical impact: Changes in number affect the baby’s ability to fight infections
2. Qualitative Disorders (Functional Defects):
◦ White blood cell numbers may be normal, but the cells don’t work properly.
◦ Examples: defective chemotaxis (movement toward infection), phagocytosis (engulfing bacteria), or
oxidative burst (killing microbes).
◦ Clinical impact: The neonate may still get infections despite normal WBC counts.

Examples
1. Impaired chemotaxis – WBCs cannot move properly toward infection.
◦ Example: Leukocyte Adhesion Deficiency (LAD)
▪ Mutation in adhesion molecules → neutrophils cannot reach infection sites
▪ Clinical: delayed wound healing, recurrent bacterial infections
2. Defective phagocytosis – WBCs cannot engulf bacteria effectively.
◦ Example: Chediak-Higashi Syndrome
▪ Lysosomal trafficking defect → giant granules in neutrophils
▪ Clinical: recurrent bacterial infections, partial albinism
3. Impaired oxidative burst – WBCs cannot kill microbes after ingestion.
◦ Example: Chronic Granulomatous Disease (CGD)
▪ Defect in NADPH oxidase → WBCs fail to produce reactive oxygen species
▪ Clinical: recurrent abscesses, granuloma formation

• Quantitative = how many cells are present
• Qualitative = how well the cells function
This distinction is important in neonatal pathology because
treatment and prognosis differ depending on whether the
problem is low/high numbers or functional defects.
• Early recognition is critical to prevent neonatal infections and
complications.

Band Cells (Non-Segmented PMNs) in Neonates
• Definition: Immature neutrophils with a band-shaped nucleus (not fully segmented).
• Normal in neonates:
◦ Neonates often have slightly higher band counts than older children or adults.
◦ Reflects the rapid production of neutrophils in response to birth stress or mild infection.
• Clinical significance:
◦ Mild increase is normal at birth.
◦ Marked increase may indicate infection (sepsis), inflammation, or stress response.
• Laboratory note:
◦ Part of total WBC count differential
◦ Used to calculate the “immature-to-total neutrophil ratio (I/T ratio)” for sepsis evaluation.

• Band cells are a
normal
component of
neonatal
hematology, but
high levels
require careful
evaluation for
infection.

Neonatal platelets
1. Platelet counts and function in newborns differ from adults
◦ Term and preterm neonates usually have normal platelet
counts (150–450 ×10⁹/L)
◦ Preterm infants may have lower counts or immature
platelet function

Neonatal thrombocytopenia is defined as
• Platelet count less than 150000 / cu.mm
• Incidence
•
Newborn : 1-5%
bm{1%} -healthy term neonates
Rest – preterm / sick /IUGR
NICU : 22-35%
(50% severe)
bm{6%} - total neonates
bm{8%} - preterm

◦ Thrombocytopenia is common in NICU(Neonatal Intensive Care Unit.
◦ ) due to:
▪ Sepsis
▪ Intrauterine growth restriction
▪ Maternal conditions (e.g., preeclampsia)
◦ Functional platelet defects may lead to bleeding despite normal counts
▪ Especially in prematurity or critically ill neonates

• Hemorrhagic disease of the
newborn also involves
platelets indirectly
◦ Vitamin K deficiency
affects coagulation factors,
and severe
thrombocytopenia worsens
bleeding

Summary
• Newborn blood is different from adults (high HbF, special RBC, WBC,
platelets).
• Anemia can be:
◦ Normal (physiologic)
◦ Hemolytic (immune or non-immune)
◦ From blood loss (iatrogenic)
• White blood cells: Too high, too low, or not working properly → infection
• Platelets & bleeding: Thrombocytopenia and vitamin K deficiency can cau
bleeding.
• Prevention & care: Vitamin K, delayed cord clamping, screening for
hemolysis.

Conclusion
• Neonates have unique blood characteristics that
differ from adults.
• Anemia, leukocyte, and platelet disorders are
common and can be serious.
• Hemorrhagic disease and hemolytic disorders
require early recognition.
• Preventive measures like vitamin K, delayed
cord clamping, and screening improve
outcomes.

References
1. McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory
Methods, 23rd Edition. Elsevier, 2021.
2. Christensen RD, Yaish HM. Hematology of the Newborn, in Nelson Textbook of Pediatrics,
22nd Edition. Elsevier, 2021.
3. American Academy of Pediatrics. Policy Statement: Vitamin K Prophylaxis in Newborns,
Pediatrics, 2020;145:e20200207.
4. Bain BJ. Blood Cells: A Practical Guide, 6th Edition. Wiley-Blackwell, 2020.
5. Mohan S, et al. “Neonatal Hematology: An Overview.” Indian J Hematol Blood Transfus,
2018;34:182–190.
6. Cunningham FG, Leveno KJ, Bloom SL. Williams Obstetrics, 25th Edition. McGraw-Hill,
2022.
7. Christensen RD, et al. “Evaluation of Anemia in the Neonate.” Clin Perinatol, 2021;48:85–
102.

hematological changes and Hematological diseases in neonates

hematological changes and Hematological diseases in neonates

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