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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-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: 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