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Platelet Transfusions
Dr Vinay H joshi MD, DM,
Fellowship NICU, PICU & Cardiac ICU
(University Of Sydney & Toronto)
Cloudnine Hospital, Mumbai
SRCC Children’s Hospital, Mumbai
Case
• 26 wks, 700gms, severe PIH, day6, on CPAP, intermittent apneas, platelets 60000/cmm
• 26 wks, 700 gms, severe HMD, day 6, sepsis, ventilated, 2 mm PDA, platelets 55000
• 26 weeks, 700gms, day 6, on CPAP, partial feeds, platelets 25000/cmm
• Thrombocytopenia is defined as a platelet count less than 1.5 lacs/cmm
• 2nd most common (after anemia) hematologic disorder of infants admitted to NICUs
• Incidence:
• 18-35% of all NICU patients
• 70% of ELBW infants (< 1000gms)
• 80% in < 600 gms
Classification of Thrombocytopenia
• Timing
• Early- within 3 days
• Late- > 4 days
• Severity
• Mild- 1.5- 1 lac/cmm
• Moderate- 1 lac- 50000/cmm
• Severe- < 50000/cmm
Andrew et al. 1992
• Thrombocytopenic infants, 2 ½ times more likely to bleed than non-thrombocytopenic infants
• Among VLBW infants, thrombocytopenia was associated with higher incidence of severe bleeding (IVH Grade III/IV) (44% Vs 16%)
Prematurity IVH
• The incidence and severity of thrombocytopenia is inversely proportional to the GA
• The smallest and most premature infants have the highest incidence of bleeding/IVH
• ~ 30% of ELBW babies have IVH, usually developed in the first week of life
Platelet transfusions Vs platelet count
• So it is accepted that these babies should receive platelets at higher threshold levels (Vs children and adults)
Are we doing it right?
• Timing and thresholds are right?
• Platelet transfusions – the only way to prevent IVH in PT/ELBW neonates?
• Do platelet transfusions really reduce the risk of bleeding?
• Are we causing more harm by UNNECESSARY platelet transfusions?
Andrew et al 1993
• Randomized controlled trial
• 152 VLBW infants, mild to moderate thrombocytopenia, first week of life
• Two thresholds, > 1.5 lacs/cmm Vs60000/cmm
• No difference in IVH (28% Vs 26%)
• Limitation: Babies with severe thrombocytopenia and > 7 days excluded
No added benefit of maintaining platelet levels > 50000/cmm Vs > 1,50000
PlaNeT-1 study- Stanworth et alPediatrics 2009
• Prospective, multicenter Observational study
• 25% of thromboctopenia, platelets < 60,000/cmm
• 9% of above patients experienced severe IVH
• 87% patients < 28 weeks and 87% occurred within first 2 weeks of life
• Secondary analysis showed babies who received platelets had fewer minor bleeds (Vs those who did not receive platelets)
• Von Linden et al
• Liberal Vs restricted platelet transfusion
• No difference in the incidence of bleeding
So is it the combination of thrombocytopenia with other factors
(clinical and lab) more predictive of risk for bleeding?
Factors contributing to IVH
• Fragile, vascularized and ill supported germinal matrix
• Fluctuations of hemodynamics-hypotension, PDA, volume boluses, ionotropes etc
• Sick infants (NEC, DIC)
PlaNeT 2 MATISSE Collaborators
• RCT, multicenter
• Platelet transfusion; High threshold- 50,000 VsLow threshold 25,000
• 660 patients, median GA 26.6wks, BWt740gms
• Primary outcomes: Death or major bleed within 28 days of randomization
Results
• Platelet Tx: 90% babies in high threshold group Vs 53% in low threshold group
• Major bleed or death: 26% in high threshold Vs19% in low threshold group (CI 1.06- 2.32, p= 0.02)
• Secondary outcomes: Higher BPD in high threshold group compared to low threshold group (63% Vs 54%, OR 1.54)
• Adverse outcomes: No difference between the groups
From available literatureConclusion…
• Limited evidence to suggest causal relationship between platelet levels and serious IVH
• No additional benefit of prophylactic transfusions to maintain higher platelet counts
• Strongest predictors of serious bleeding were:
• GA < 28 weeks
• Post-natal age < 10 days
• Severe sepsis/ NEC
• Prophylactic platelet transfusions (for higher thresholds) can increase mortality, IVH and BPD
From available literaturConclusion…
Harmful effects of platelet transfusions
• Infections: bacterial, viral, CMV
• Inflammation: the supernatant fluid contains inflammatory mediators (VEGF, PAF, IL-6, IL-8)
• GVHD- immunocompromised
• TRALI
• Tilting towards prothrombotic state (adult platelets)
• Volume overload
Transfusion Related Acute Lung Injury(TRALI)
• Potentially Life threatening complication of blood transfusion
• In adults, reported mortality ~ 5-10%
• Manifests in the form acute respiratory distress requiring escalation of respiraotrysupport
• Two Hit theory: Neutrophils and HLA
29
16
6
0
5
10
15
20
25
30
Nu
mb
er o
f
ep
iso
de
s
Any One
criterion
Any Two
criteria
All Three
criteria
Criteria: FiO2 > 10%, MAP >2,
New mode of ventilation
TRALI Episodes by Number of Diagnostic Criteria
Does Transfusion Related Acute Lung Injury (TRALI) Occur In Newborns
V Joshi1, P Joshi1, K Webert2, J Cairnie1, N Heddle2, T Sabourin1, M Blajchman2 and H Kirpalani1
Department of Neonatology1 and Transfusion Medicine2, McMaster Children’s Hospital, Hamilton, ON, Canada
Background
• TRALI is a potentially
life-threatening complication of blood
transfusion in adults. (Incidence-1:5000
transfusions).
• The reported mortality is approximately
5-10% of TRALI cases.
• Only two cases of TRALI occurring in
neonates have been reported in
literature1,2.
Objectives
• To determine if TRALI occurs in
neonates;
• If it occurs, to estimate its incidence.
Design/Methods
• In a level III NICU, we prospectively
observed all consecutive newborns who
received a blood product transfusion
from June 2005 to October 2005.
• As this was a pilot study to establish
whether the phenomenon might exist, we
formed a convenience sample of 200
consecutive blood product transfusions.
• Information recorded: patient
demographics, blood component
received, indication for blood component
therapy and cardio-respiratory status (4
hours prior to and 6 hours post-
transfusion).
We defined TRALI as present if,
compared to the average 4 hours
pre-transfusion, any of the following
events occurred in the 6 hours
following the start of the transfusion:
(i) An increase in FiO2 of >10% for
>15 minutes;
(ii) An increase in mean airway
pressure of >2 cm H2O;
(iii) A new mode of ventilation
initiated by a worsening lung
condition (increased frequency of
apnea with bradycardia; or RR
increase by >10/min).
Results• 200 blood products were
administered to 75 newborn infants
(2.6 per infant).
• 30 received a single transfusion and
45 babies received multiple
transfusions.
• TRALI was seen in 29 transfusion
episodes (15%). Of these, 23 episodes
were associated with PRBC, 4 with
platelets, and 2 with FFP.
Type of Blood Product Transfused
4%(8) 3% (5)
73%(148)
20%(39)
PRBC
Platelets
FFP
Others
Mean (SD) FiO2 requirement in the 16 babies who had a change of >10% FiO2
4 hrs pre-
transfusion
Start of transfusion Peak of FiO2 rise after
start of transfusion
6 hours post-
transfusion
42.6 (13.3)† 44.3 (17.7) †*
p† >0.05
72.7 (22.2) *#
p *=0.0004
47.2 (20.3) #
p # =0.009
0
20
40
60
80
100
120
-4 -3 -2 -1 0 1 2 3 4 5 6 7
Time in ho urs
FiO
2 %
TRALI Episodes With Increase In FiO2 By > 10%
Conclusion15% incidence of TRALI was noted in
our study as diagnosed by predefined
criteria.
Future directionSince this study was from a single
institution, a multi-center evaluation
would help confirm this is a true entity
in newborns.References1. O’Connor JC, Strauss RG, Goeken NE, Knox LB. A near-fatal reaction during granulocyte transfusion of a neonate. Transfusion 1988; 28:173-176.2. Gloster ES, Ranu S, Wang Y. Transfusion related acute lung injury (TRALI) type reaction in a neonate. Transfusion 2004; 44; supplement 108 A, SP263.
Fig.1.
Table.1.
Fig.2.
Fig.3.
Total Transfusions 200 TRALI like episodes 29 (15%)
Packed Red cells 148 (74%) 23 (16%)
Platelets 39 (20%) 4 (10%)
Fresh Frozen Plasma 8 (4%) 2 (25%)
Others 5 (2.5%) Nil
• Platelet transfusions associated with highest incidence of complications among all components
(Slonim AD. Transfusion 2008,
Stainsby D. UK SHOT scheme Br J Hematol 2008)
• Strong association between number of platelet transfusions and increased neonatal morbidity and mortality (Del Vecchio 2001, Garcia MG 2001, BonifacioL 2007, Kenton AB 2005)
Limitation of the definition
• Can we use same conventional cut offs to define thrombocytopenia in preterm infants?
• Is it really thrombocytopenia? Or normal values for PT/ELBW infants?
Weidmeier SE et al 2009, 47,000newborns, 22-42 weeks GA
Mean
95th centile
5th centile
Need to redefine thrombocytopenia in PT/ELBW infants
1.041.25
Summary
• Preterm thrombocytopenia needs better definition, reference range
• No correlation found between platelet transfusion and timing of IVH
• Prophylactic administration of platelets did not prevent/reduce IVH
• Platelet transfusions are associated with complications (infection, inflammation, TRALI)
• Keeping higher thresholds for platelet transfusion was associated with increased mortality, IVH and BPD
So we infer…..
• Need to shift towards restricted (Lesser) platelet transfusion practice in babies without significant bleeding within last 72 hours