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A Practical Guide to Haemostasis


Paediatric Reference Ranges


Introduction

The coagulation system in the neonate is immature compared to the adult system (or the child at 6 months of age) but remarkably it results in few problems for the healthy term neonate. Reference ranges must be used for neonates and for the pre-term infant as many of the proteins involved in haemostasis vary with age.

Below is a summary of the proteins/Tests that are low/prolonged in the neonate

Screening Tests

Testy Comment
PT Similar to adult reference range and does not change throughout childhood
APTT Low at birth - generally reaches adult values at 6-12 months of age
Thrombin Time Prolonged at birth due to the presence of 'fetal' fibrinogen
Fibrinogen Levels are normal at birth but a fetal fibrinogen due to altered sialic acid content can prolong the Thrombin Time


Procoagulant Proteins

Protein Comment
Factor II All the Vitamin K dependent clotting factors are low at birth and reach adult values by 6 months of age [See also Protein C and S below]
Factor VII
Factor IX
Factor X
Factor V Normal at birth
Factor VIII Normal at birth
Factor XI Low at birth.  Reaches adult levels at 6-12 months of age
Factor XII Low at birth. Reaches adult levels at 6-12 months of age
Von Willebrand Factor [VWF]
Ag and Act
Normal at birth
Factor XIIIa
Factor XIIIb
Borderline/Normal at birth
Borderline/Normal at birth
Pre-kallikrein Low at birth. Reaches adult levels at 6-12 months of age


Natural Anticoagulants

Protein Comment
Protein C Low at birth and although in many cases Protein C is normal by 6 months of age, in some individuals it may take longer.
Heterozygous Protein C deficiency can be difficult to diagnose in the neonatal period due to the wide variation in levels. In contrast homozygous deficiency is readily diagnosed due to a complete absence of Protein C.
Protein S Total Protein S levels are low at birth. Protein S exists in the neonate primarily in the Free form due to low levels of C4b binding protein.
Free Protein S levels are low at birth and reach adult values at ~4 months of age.
Antithrombin Functional Antithrombin levels are low at birth and may be further reduced in the sick neonate. Levels normally reach adult values at ~3 months of age.
Factor V Leiden
Prothrombin G20201A Mutation
These mutations should be identified by DNA analysis if indicated.

APCr screening assays can be unreliable due to the variation in FVIII levels in the neonate.


Platelet Membrane Glycoproteins

Formal platelet function testing in the neonate is difficult using conventional platelet aggregometry due to the large volume of blood that are needed to generate Platelet Rich Plasma [PRP].  The FPA-100 and Flow cytometry can be useful in this situation.  Platelet membrane glycoproteins are fully developed in the term, and premature neonate and flow cytometry can be very useful in establishing the diagnosis of the congenital disorders such as Bernard Soulier disease and Glanzmann’s Thrombasthenia.

Fibrinolytic System

Protein Comment
Plasminogen Plasminogen levels are low at birth (~50% that of the adult).
T-PA Raised at birth
α2-Antiplasmin Levels are normal at birth
PAI-1 Raised at birth
α2-macroglobulin Levels are raised in children


Thromboelastography [TEG] in term neonates

The TEG in neonates differs from older children and adults with shortened R and K time but an increased rate of fibrinolysis [increased Lys30 and CLI].  The reference ranges and cut points for citrate-modified and heparinase-modified TEG can be used to diagnose and evaluate haemostasis in term neonates. The TEG measurements from term neonates are no different in neonates whether they are delivered vaginally or by caesarean section