Neonatal Haematology

DR. AGELEBE.E Bowen University Teach

Hosp Ogbomoso

Fetal circulation

O2 blood from placenta

Umbilical vein(50%) Hepatic circulation

Bypassesliver

Ductus venosus

IVC

RA (ovale)

SVC LA

TV

RV

Lungs (10%)PA

LV

PDA

DescendingAorta

Umbilical arteries

Blood from lower part of body

Ascending aorta

Upper part of body

Lower partOf body

SPO2 45%

Globin Synthesis in Embryo, Fetus and Adult

Regulation of Erythropoiesis

Retic count is 3 -7%

Fetal haemoglobin increases with gestational age, at

about 28 weeks, fetal Hb is about 45%.

Normal Hemoglobin and MCV Values in Term

Infant

Hb MCV

(g/dL) (fl)

Day 1 19.0±2.2 119 ±9.4

Anatomy /PhysiologyIn-utero fetal blood volume is 115ml/kg(75ml baby & 40ml placenta)

• At birth : 80 – 90ml/kg.

• After birth, SPO2 rises to 95%

• Newborn - 90 days

• Preterm - 75 days

• Adult - 120 days

• Hb nadir occurs at 8 – 12 weeks in term

• 12 weeks PCV= 11.3 ±0.9 MCV= 88 ±7.9

• HbA /HbF starts to increase

• 2,3 –DPG increases

• Oxygen delivery to tissue increases

Haematological Indices

HAEMATOLOGICAL INDICES

1. Haemoglobin (g/dl)

Term 14 – 20

Preterm 14 at 28 weeks of gestation. (It is 1 -2g/dl less.)

2. Haematocrit 45 – 65%, (lower in preterm)

3. White blood cells (Varies with post-natal age)

Day 1 6,000 – 35,000/µL

Week 1 8,000 – 16,000/µL

First month 6,000 – 14,000

FBC Differentials Neutrophils %

Day 1 50 – 80 (Neutrophil predominance)

Day 4 35 – 60 (Approx % of lymphocytes)

Day 7 35 – 45 (Is falling)

3 months – 7 years 25 – 45 ( typical childhood lymphoctes predominance

Lymphocte

%

Day 1 31

Day 7 41

Day 14 48

Retic count%

Day 1 2 – 8Day 7 0.51 month 0 .2– 0.5

Neonatal anaemia

• The most common haematological disoder

• Reduced haemoglobin below normal for gestational and post-natal age.

• Different classification

Aetilogical Classification of Anaemia(1)

A. Blood loss fetal to fetal, feto-maternal, traumatic delivery

B. Excessive blood destruction

1. Intrinsic factors

a. Enzymatic defect: G6PD deficiency, pyruvate kinase

b. Defects of membrane: spherocytosis, elliptocytosis

c. Defects of hemoglobin

Synthesis anomaly: thalassemia

Aetilogical Classification of Anaemia(1)

2. Extrinsic factors

a. Immune mechanisms: Rh, ABO incompatibility, autoimmune hemolytic anemia

b. non-immune mechanisms: infections

C. Decreased production

1. Deficiency of substrates: iron, folic acid

a. Primary: aplastic anemia

Classification Based on Onset Time

• Early-onset Anaemia

• Late-onset Anaemia

EARLY-ONSET ANAEMIA

• Occurs in first few days after birth

• Most frequently due to haemolytic disease or haemorrhage

Causes Haemolytic disease

• Rhesus haemolytic disease

• ABO haemolytic disease

• G6PD deficiency – is common here, 20 – 25% of male population

• Infections – causes suppression of bone marrow and excessive haemolysis

EARLY-ONSET ANAEMIA

Causes

• Neonatal haemorrhage –

Birth trauma -

– Cephal haematoma

– Sugaleal haematoma

– Ruptured Liver or spleen etc

– Intra-abdominal haemorrhage

– Fracture of femur

EARLY-ONSET ANAEMIA

• Maternal infections e.g parvo-virus

• Others

– Spherocytosis

– α-thalassemias

– Fetal haemorrhage

- Abruptio placentae

- Vasa praevia

– Fetomaternal transfusion

– Twin-twin transfusion

– Congenital hypoplastic anaemia

Clinical Presentation

History • Antepartum haemorrhage

• Multiple delivery

• Instrumental delivery

• Poor feeding

• Breathlessness

Physical examination

• Colour

• Bruises – scalp, shoulder

• Cephal haematoma – is limited at suture line

• Rigid abdomen

• Small pulse volume

• Tachycardia

• Hypotension

• Tachypnoea

• Fever /Hypothermia –suggesting infections

Management

Investigation

• PCV

• WBC - pancytopaenia is a feature of aplastic anaemia

• Blood film – may show spherocytosis

Treatment

• Asymptomatic – leave the child

• If in shock (and the child is term) i.e BP < 25mmHg, PCV < 30%, pH < 7.1 Immediate transfusion with 15 – 20ml/kg of whole blood over 5 – 10minutes ( if it is due to haemorrhage)

Management Treatment

• If not in shock, but anemia is severe

• Transfuse 20ml/kg over 2 – 3hours with IV frusemide, 2mg/kg

• or

• 10 – 15ml/kg (2 -3 mls/kg/hour) partially packed

• Note : 2ml/kg of packed cells raises haemoglobin by 0.5 – 1g/dl or PCV of 10%.

• Very severe anaemia Hb < 8g/dl or the child is in congestive cardiac failure

• Single volume EBT with packed cells

• The procedure involves – calculating the total volume

– Taking of blood in aliquots (10mls for each round)

LATE ONSET ANAEMIA

This appears later in the neonatal period

• Causes– Mild haemorrhagic disease of the newborn

– Haemolytic disease of the newborn – ABO incompatibility (Note Rhesus isommunization often presents as early-onset anaemia

– Chronic blood loss e.g GI bleeding (Merkel’s diverticulum)

– Infection – causing DIC by the toxins which damage to the endothelium, stimulating consumption coagulopathy. It also depresses bone marrow.

– Chronic infections e.g. rubella, parvovirus

– G6PD deficiency

– Spherocytosis

– α – thalassemia

– Congenital hypolplastic aplasia

– Repeated venipuncture

Management

• If it is severe, do exchange blood transfusion

•

• Transfuse with straight forward transfusion if

moderate

• If mild would need haematinics

ANAEMIA OF PREMATURITY• An exaggeration of physiological anaemia

• Common in preterm because of lower RBC life span and higher tendency to be sick.

• Reasons For Higher Incidence Rate in Preterm

• Minimum value of PCV is reached earlier in preterm than in term babies which is

about 6 weeks (1- 3 months)

• Their RBCs have reduced life span

• Iatrogenic – samples for investigation.

• Because of relative more rapid somatic growth rate.

• Due to Vitamin E deficiency – from relative fat absorption

• Preterm infants start to produce erythropoietin when Hb falls to 7 – 9g/dl in contrast to

10 – 11g/dl in term infants because their tissues require lower oxygen requirement.

Clinical Presentation

• May be asymptomatic

• Pallor

• Apnoea

• Poor weight gain

• Tachypnoea

• Tachycardia

• Re-opening of Patent ductus arteriousus

Management

• If symptomatic – give blood transfusion slowly with

10ml/kg of packed cells over 1 – 3 hours. Note,

haematinics are not used because it takes longer time

to act if moderate to severe.)

Prevention

• Adminstration of folic acid 5mg weekly to babies < 2kg from 2 weeks of age.

• Adminstration of α – tocopherol acetate (Vit E) daily to babies < 1.5kg from 2 weeks of age

• Administration of Ferous sulphate, 50 mg/day or elemental iron 6mg/kg/day from 2kg or 2 weeks of age.

• Use of recombinant human erythropoietin, 100 -22iu/kg, given 5d /week, 400u/kg/d, 3d/week + iron + vit. E. This is forcing baby to start erythropoieis, after which iron can be given in this case.

Polycythaemia

• Definition

• Is venous PCV > 65% ( the more the PCV above 65%, the low the oxygen carrying capacity due to increase in viscosity.

• Aetiology

• Placenta insufficiency – due to placental infarcts e.g in diabetes mellitus

• Maternal –fetal transfusion – due to delayed cord clamping

• Twin-twin transfusion e.g monozygotic twins

• Infants of diabetic mothers (IDM) - due to hypoxia caused by vascular problems

• Dehydration

• Others– Congenital adrenal hyperplasia

– Trisomy 13, 18, 21

– Neontal thyrotoxicosis

– Becwith-Weidmann syndrome

– Maternal drugs e.g propanolol

•

Clinical Presentation

General

• Plethora

• Jaundice

• Cyanosis (≥ 5g/dl of deoxygenated blood) -may be a cause or effect.

• Prolonged capillary refill

Respiration

• Tachypnoea

• Dyspnoea

GIT

• Feeding problems

• Necrotizing enterocolitis

CNS – Mostly undesirable

• Irritability

• Jitteriness

• Lethargy

• Seizures

Investigation Complications

• Thromboembolism

• Pulmonary haemorrhage

• Congestive cardiac failure

• Brain damage

•Bilirubin -

hyperbilirubinaemia

•Blood sugar –

hypoglycaemia

•Serum calcium –

hypocalcaemia

•Chest X-ray – shows

prominent pulmonary

vascular markings

Management

• If PC < 70% and the child is asymptomatic

• Admit and observe

• Ensure no dehydration

•

• If < 70% and symptomatic

• - Do erythropoiesis ( note, not plasmapharesis)

•

• If > 70% and asymptomatic

• Treat

Management Con’t

Calculation

Vol(ml) = bld vol x (observed-desired pcv)

actual pcv

• Blood Volume = 80 – 90ml X Weight

The following can be used– plasma

– Fresh frozen plasma

– Normal saline

– Haemacel

Management Con’tPrecaution

• At any time, don’t take > 25% of blood

volume.

Bleeding Disorders

Tests of coagulation:

• PT ; Extrinsic system

• Dependent on factors II VII, IX, X (1972) measures vit K def.

• Normal range is 13 – 20s

• PTT; Measures intrinsic pathway factors XII, XI, VII, X, V, II, I

• Prolonged in DIC, heparin therapy, haemophylia and severe vit k def

• In Vitamin k deficiency, both PT & PTTK are done abnormal

Bleeding Disorders

Tests of coagulation:

PT ratio ( Test/Control )INR

• Normal range = 0.9 – 1.2.

• Fibrinogen – Normal range is 150 – 300mg/dl

Bleeding time

• Platelet function

HAEMORRHAGIC DISEASE OF THE NEWBORN

HDNIt is due to deficiency of vitamin K in newborn.

• Normally, the gut of babies are sterile and breast milk is not rich in vitamin K.

• It takes about a week for the baby to acquire gut flora.

• Vitamin K received from the mother disappears after few days, 2 – 7days, leading to the inactivation of vitamin K dependent factors, thus prone to HDN.

• It may result into provoked or unprovoked bleeding.

• The common sites of haemorrhage are :

– GIT

– Nose

– Cord

– Intracranial

– Circumcision

– Trauma

HDN• Early HDN

- Occurs < 24 hours of age. Here, you should exclude other possible causes

•

• Late HDN

• Occurs > 1 week

•

• Predisposing Factors to Early or Late HDN

• Birth Asphyxia

• Maternal drug ingestion e.g. phenobarbitone, aspirin, anticoagulant (Coumadin) – leading to vitamin K deficiency in the mother

• Exclusive breastfeeding – since breast milk is not rich in vitamin K

• Broad spectrum antibiotics – reduce the normal flora in the gut

• Total parenteral nutrition – delays the acquire of normal gut flora through oral feeding.

HDN Con’t

Clinical Presentation

• Bleeding – provoked or

unprovoked

• On examination, patient

may look well in the

absence of any other

comorbidity.

•

Investigation

• Packed cell volume

• FBC - normal

• Platelet count – normal

• Prothrombin time -

prolonged

• PTTK – prolonged

• Fibrinogen – normal

• FDP – normal

Treatment of HDN

Non-severe

– Give Intravenous Vitamin K1, 1 – 5mg stat. ( K2 & K3 are

not used if patient is G6PD deficient because they cause

haemolysis.

Severe & Life non-threatening

• Intravenous Vitamin K stat

• Double volume EBT with fresh whole blood - to remove

inactivated clotting factors, called Protein-induced Vitamin K

factors with vitamin K replenishment.

Note

• Single volume EBT – 65%

• Double volume EBT – 83 -85%. It is often used for it maximal

effect.

Prevention

• Rotine intramuscular vitamin K1, 1 mg stat, to every newborn baby. For preterm, the dose is 0.5mg stat.

• For special babies (with any of the conditions listed above e.g total parenteral nutrition), you continue to give 0.5mg / week until the baby starts feeding.

DISSEMINATED INTRAVASCULAR

COAGULOPATHY (DIC)Predisposing Factors

These are causes of generalised vascular damage

• Severe birth asphyxia

• Septicaemia

• Hypothermia

• Hypotension

• Acidosis

• Hypoxia

Pathogenesis

• Due to consumption of clotting factors

DICClinical Presentation

• Provoked bleeding - from puncture sites

• Unprovoked bleeding e.g petechiae, spontaneous massive bleeding form orifices.

• Investigation

As in the bleeding disorders

• Treatment

• Treat the underlying cause

• Specific treatment

• Give Platelet concentrate /Platelet rich plasma + transfusion with fresh frozen plasma using 10 – 15ml/kg

• Give Vitamin K1 intravenously

• If severe do EBT with fresh whole blood – to remove the toxins & FDP which causes haemorrhage

Disease

Clinica

l state

Platele

t

PT PTTK Other tests ( to

confirm)

1. Haemorrhagic

disease of the

newborn

Well Normal ↑ ↑ Fibrinogen/FDP – Normal, because there is no excessive breakdown of clots

2. Idiopathic

thrombocytopaenic

purpura (ITP

Well ↓ Normal Normal Maternal platelet

count – decrease confirms it

3. Large Haemangioma Well ↓ Normal Normal Maternal platelet

count – normal

4. Bone Marrow

Hypoplasia Well ↓ Normal Normal Peripheral blood film –

shows pancytopaenia

5. Haemophilia Well Normal Normal ↑ Factors 8 & 9 Assay 6. Liver disease Sick Normal ↑ ↑ Albumin, Fibrinogen &

LFTs are deranged

7. Intrauterine TORCH

Infection Sick ↓ (may

be) N or ↑ N or ↑ Fibrinogen, Albumin

8. Infections Without

DIC e.g Septicaemia

Sick ↓ Normal Normal FBC, Blood culture

9. Infections + DIC (or in any cause of DIC )

Sick ↓ ↑ ↑ Fibrinogen - ↓

FDP - ↑

PBF – fragmented rbc due

to trapping

a-thalassemia

a-globin Cluster

Hydrops Fetalis Syndrome

– Most Hb- Hb Barts, unable to deliver O2 to tissues

– Tissue hypoxia & anemia

– Massively enlarged placenta

– Heart failure, edema anasarca interferes with organogenesis, congenital malformations

– Extramedullayerythropoiesis

• Thank You