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

Causes of Thrombocytopenia

Thrombocytopenia and Risk Of Serious Hemorrhage in PT infants??

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)

Transfusion practices in Europe and NA Cremer et al Transfusion 2011

Normal PT Sepsis l PT

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)

Nadir platelets were similar in NO Bleed, SMALL Bleed and SEVERE bleed

• 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

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…

Do platelet transfusions increase mortality???

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

So let’s think think think …before reaching out for that platelet bag!!

Thank You