Platelets and PlaNeT-2

Platelets and coagulation

Damaged endothelium

PLATELETS

Adenosine diphosphate

(calling effect)

Collagen

Fibrinogen

↓↓

PLATELETS

PLATELETSPLATELETS

PLATELETS

PLATELETS

↓↓

Thrombocytopenia:

Platelet count of <150x109/L in a neonate of

any gestational age

Severe thrombocytopenia:

Platelet count of <50x109/L

Thrombocytopenia

Neonatal Thrombocytopenia

Prevalence: 1 - 5% of all newborns

25% NICU admissions

5-10% severe thrombocytopenia

Neonatal Thrombocytopenia: Main causes

Fetal:

Alloimmune

Congenital infection

Aneuploidy

Early-onset (<72 hours):

Chronic fetal hypoxia

Perinatal asphyxia

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

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: Platelet thresholds

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.

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: Inclusion criteria

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)

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 weeksAt SD7, SD14, SD21 and SD28

PlaNeT-2: Data collection (II)

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)

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

A SAE is an adverse event that results:

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: End of study

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 22 173-186.

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

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