Platelets and PlaNeT-2
Platelets and coagulation
Damaged endothelium
↓
Collagen
PLATELETS
↓
PLATELETS
PLATELETS
Adenosine diphosphate
(calling effect)
Fibrinogen
PLATELETS
PLATELETS
PLATELETS
Thrombocytopenia
Thrombocytopenia:

Platelet count of <150x109/L in a neonate of
any gestational age
Severe thrombocytopenia:

Platelet count of <50x109/L
Neonatal Thrombocytopenia

Prevalence: 1 - 5% of all newborns

25% NICU admissions

5-10% severe thrombocytopenia
Neonatal Thrombocytopenia:
Main causes
Fetal:
Early-onset (<72 hours):

Alloimmune

Chronic fetal hypoxia

Congenital infection

Perinatal asphyxia

Aneuploidy

Perinatal infection
Late-onset (>72 hours):

Late-onset sepsis

NEC
Neonatal Thrombocytopenia
Why don’t neonates up-regulate platelet production
when they have consumptive disorders?
?
? Developmental deficiency
?
? Disease process
?
?
? Cell-intrinsic differences
?
?
? Hematopoietic environment
?
?
Neonatal Thrombocytopenia:
In practice
Current national transfusion guidance based on
consensus rather than evidence
British Committee for Standards in Haematology (2004)
United Kingdom Blood Services (2007)
Survey in the UK showed wide variation in platelet
transfusion practice
Chaudhary and Clarke (2008)
PlaNeT-1

Prospective observational study of NICU
admissions with platelet counts <60x109/L

7 NICUs

169 neonates studied for 7 days, or until platelets
>60x109/L

Platelet count

Haemorrhage

Platelet transfusions

Outcome
Stanworth et al (2009)
PlaNeT-1: Haemorrhage
PlaNeT-2
Platelets for Neonatal Transfusion - Study 2
PlaNeT-2
Two-stage, randomised, parallel group, superiority trial.
Aim: to compare two different platelet count thresholds for
prophylactic platelet transfusion to preterm neonates.
Primary Outcome:
 Proportion of patients who either die or experience a
major bleed up to and including study day 28.
PlaNeT-2: Study design (II)
Secondary Outcomes:







Proportion of neonates surviving to home following
a major bleed
Mortality prior to day 28
Major bleeds by day 28
Platelets transfused to study day 28
Length of hospital stay
Transfusion-related adverse events
Neuro-developmental outcome
PlaNeT-2:
Choosing platelet thresholds
Last RCT done by Andrew et al (1993) assessed
50-150x109/L vs. >150x109/L
PlaNeT-1 (2009):

Most transfusions given at platelets 10–50x109/L.

50th and 90th centile pre-transfusion platelet counts
27 and 48x109/L.

42% transfusions <25x109/L and 92% <50x109/L
PlaNeT-2: Platelet thresholds

Arm A Standard: transfuse platelets at
<25x109/L (330 neonates)

Arm B Intervention: transfuse platelets at
<50x109/L (330 neonates)

Dose: 15ml/kg for both arms
PlaNeT-2:
Additional Platelet Transfusions
May be considered under the following circumstances:

Therapeutically to treat moderate, major or severe
bleeding but not for minor bleeding.

Prior to planned invasive procedures as below only

Suprapubic aspiration

Lumbar puncture

Major surgery where haemostasis may be critical to
outcome.
PlaNeT-2: Inclusion criteria

Admission to a participating NICU (includes
postnatal transfers)

<34 weeks GA at birth

Platelet count of <50 x109/L

Cranial ultrasound scan: undertaken <6 hours
before randomisation to exclude recent major IVH
PlaNeT-2: Exclusion criteria

Major/life-threatening congenital malformations

Recent major haemorrhage within the last 72 hours

All fetal intracranial haemorrhages

Known immune thrombocytopenia

Neonates unlikely to survive

Neonates not given parenteral vitamin K
PlaNeT-2:
Consent and randomisation
Consent:


Parents/ guardians will be counselled when platelets <100x109/L.
Written, informed consent will be obtained.
Randomisation: only when platelet count <50x109/L.

For neonates with an initial platelet count of <50x109/L, parents
will be approached for consideration of immediate study
participation.
PlaNeT-2: Data collection (I)
When the consent is signed and platelets <50x109/L:

Pre-randomisation form (F1)

Eligibility for randomisation (F2)

Current medical conditions & previous major bleeds (F3)

Randomisation (F4)
PlaNeT-2: Data collection (II)

Daily Bleeding Assessment Tool (BAT) (F5)


During Ward Round
Daily until Study Day (SD) 14

Daily Platelet Count (F6) until SD28

Weekly Data Collection (F7)


Weekly from SD14 until the end of the study
Cranial Ultrasounds: Weekly for 4 weeks
At SD7, SD14, SD21 and SD28
PlaNeT-2: BAT

Completed for 14 days
during Ward Round

Nursing records and
communication
PlaNeT-2: Data collection (III)
Forms for completion as required:






Platelet Transfusion Data (F8)
NEC/Sepsis Form (F9)
Discontinuation of Treatment Allocation (F10)
Major/Severe Bleed (F13)
Serious Adverse Event (F14)
Serious Platelet Transfusion Related Adverse Event (F15)
PlaNeT-2:
Serious Adverse Events (SAE)
A SAE is an adverse event that results:

in death

is life-threatening and requires hospitalisation
or prolongation of existing hospitalisation
(including readmission within 28 study days if
discharged home earlier)

there is a likelihood of persistent or significant
disability or incapacity
PlaNeT-2: End of study

Data collection will cease and an End of Study
Form will be completed at 38 weeks gestational
age or time of discharge home
PlaNeT-2: Data collection (cont.)
End of study:

Cranial Ultrasound at End of Study (F11)

End of Study (F12)
Summary

Platelets are responsible for the initial cessation of bleeding

Thrombocytopenia in NICU is common and its reasons
unknown

PlaNeT-2 is a trial to compare two platelet count threshold for
prophylactic transfusion

PlaNeT-2 aims to improve platelet transfusion practice
References










Andrew M, Vegh P, Caco C, Kirpalani H, Jeffries A, Ohlsson A, Watts J, Sagial S, Milner R, Wang EA.
(1993) Randomised controlled trial of platelet transfusions in thrombocytopenic premature infants.
Journal of Pediatrics 123 285–291.
British Committee for Standards in Haematology (2004) Transfusion Guidelines for neonates and older
children. British Journal of Haematology 124 433-453.
Chaudhary R, Clarke P. (2008) Current transfusion practices for platelets and fresh, frozen plasma in
UK tertiary level neonatal units. Acta Pædiatrica 97(1) 135.
Manco-Jonhson M, Rodden DJ, Collins SM. ‘Newborn hematology’, in Merenstein GB, Gardner SL.
Handbook of Neonatal Intensive Care. 6th ed. Mosby Elsevier: St. Louis, pp.521-547.
Roberts I, Stanworh S, Murray NA. (2008) Thrombocytopenia in the neonate. Blood reviews 22 173186.
Roberts I, Murray NA. (2003) Neonatal thrombocytopenia: causes and management. Archives of
diseases in childhood - Fetal and neonatal edition 88 F359-F364.
Sola-Visner M, Sallmon H, Brown R. (2009) New insights into the mechanisms of nonimmune
thrombocytopenia in neonates. Seminars in Perinatology 33(1) 43-51.
Sola-Visner M, Saxonhouse MA, Brown R. (2008) Neonatal thrombocytopenia: what we do and don’t
know. Early Human Development 84 499-506.
Stanworth S, Clarke P, Watts T, Ballard S, Choo L, Morris T, Murphy MF, Roberts I (2009) Prospective,
observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics 124 826-834.
United Kingdom Blood Services (2007) Handbook of Transfusion Medicine. 4th ed. Norwich: The
Stationary Office. [online]. Available from:
http://www.transfusionguidelines.org.uk/index.aspx?Publication=HTM
Thank you!