Transcript platelet transfusion in oncohaematology

PLATELET TRANSFUSION
IN ONCOHAEMATOLOGY
9th Maghreb Haematology Conference
Sousse 25-26 May 2012
Dr.René TARDIVEL
Etablissement Français du Sang
Indications for platelet transfusion
Central thrombocytopenia together with treatment of
the cause
Thrombopathy, occasional
Peripheral thrombocytopenia, exceptional
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Platelet concentrates (1)
Principal characteristics
Origin
Composition
APC
RPP
Cell separators
From total blood
CLP or BC
1 donation
4 to 6 donations
2 to 8
3 to 5
200-400 or more
200-350
Quantity of platelets
in 1011
Volume/ml
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Platelet concentrates (2)
Principal characteristics
APC
RPP
Separators
•Haemonetics MCS ++
•Terumo BCT Trima
•Fenwal Amicus
•Fresinus Comtec
2 products:
• PRP
• CLP or BC
Several program options by
separators
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2 techniques:
• manual
• automatic
-Orbisac
-TACSI
Platelet concentrates (3)
Storage
5 days (7 days in certain countries in the event of
bacterial detection or attenuation of pathogens)
Continuous agitation
20-24 °C
concentration: 1.2-1.5.106/mm3 (recommendations)
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Platelet concentrates (4)
Possible transformations
APC
RPP
Leukocyte reduction
+
+
Stored solution
+
+
Irradiation
+
+
Plasma removal
+
+
Reduction of volume
+
+
Viral attenuation
+
+
Paediatric preparation
+
+/Mixtures of 2 units
Cryoconservation
+
-
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Platelet concentrates (5)
Possible qualifications
APC
RPP
Negative CMV
+
+
Phenotype HLA, HPA
+
-
Compatibility test
+
-
Page 7
Platelet concentrates (6)
CPA or RPP
No difference in effectiveness
No difference in frequency of immunization
No product superior to another, but one may be better adapted to
the patient
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Platelet transfusion
indication
Preventive or curative?
Page 9
Platelet transfusion
indication (1)
Curative
Patient presenting a haemorrhage
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Platelet transfusion
indication (2)
Preventive
To prevent bleeding associated with thrombocytopenia
and/or thrombopathy in a curable patient or a patient
with a prolonged life expectancy (bone-marrow
transplant, induction of L A,…)
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Platelet transfusion - Preventive
Dose (1)
Numerous studies seems to show the advantage of strong doses of
4 to 5 10 11
Norol F and coll: Platelet transfusion has dose response study
Blood 1998; 98:1448 - 1453
Klumpp TR and coll: Clinical consequences of alterations in
platelet transfusion dose: prospective, randomized, double-blind
trial transfusion 1999; 39:674 - 681
Sensebe et al: The efficacy of high-dose patient transfusions of
platelets in hematology thrombocytopenic patients: result of
prospective, randomized, open blinded end point (PROBE) study
Blood 2005 105: 862-864
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Platelet transfusion - Preventive
Dose (2)
However, other studies show that a low dose 2-3 1011 can also be
effective
Tinmouth A et al: Low-dose prophylactic platelet transfusions in
recipients of an autologous peripheral blood progenitor cell transplant
and patients with acute leukemia: a randomized controlled trial with
sequential Bayesian design. Transfusion 2004; 44: 1711-1719.
Heddle NR et al (Best ISBT Working party) Study STOP low dose 1.5 3.1011 versus standard amounts 4-6.1011. Study stopped in 2008
because of the higher frequency of haemorraging in the low-dose group
 Slichter S et al: Dose of Prophylactic Platelet Transfusions and
Prevention of Hemorrhage N England journal of medicine 2010;
362:600 - 613
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Platelet transfusion - Preventive
Dose (3)
Study PLADO (Optimal Platelet Dose Strategy for Management of
Thrombocytopenia)
3 doses of platelets: 1.1-1011/m2
2.2-1011/m2
4.4-1011/m2
Low doses involve a reduction in the transfused platelets but
increases the number of transfusions (5 versus 3 for average and high
doses)
Weak or strong doses do not have an effect on the frequency of the
bleedings
No significant difference when with the number of days before
appearance of grade 2 bleeding or higher, no matter what the dose
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Platelet transfusion - Preventive
transfusional thresholds (1)
Pietersz R.N.I International Forum –Prophylactic platelet transfusion –
Vox Sanguins 2012
14 responses by different countries
In the absence
and
of risk factor
10.109/l (except Russia and in certain indications from Japan
the Netherlands: 5-109/l
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Platelet transfusion - Preventive
transfusional thresholds (2)
In
the event of risk factors
Fever >38.5°C, evolutionary sepsis, coagulation
anomaly, thrombopathy, anaemia, mucite,
extensive purpura, haemorrhage inside the eye,
HTA, anatomical lesions
Threshold up to 20.109/l
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Platelet transfusion - Preventive
transfusional thresholds (3)
Other
situations
Invasive techniques: catheter, implantable
chamber, fibroscopy, biopsy, bronchoalveolar washing
Surgery, severe haemorrhage ,DIVC,…
Threshold raised to 50.109/l or above
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Platelet transfusion
Dose in practice
Recommendation
AFSSaPS or ANSM
• 0.5.1011 for every 7 kg of patient weight
• (or average dose suggested in PLADO study)
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Platelet transfusion
Evaluation of effectiveness
- Curative:
Stopping bleeding
- Preventive:
 Increase in platelet count after
transfusion
 Duration of transfusional effectiveness (3-4 days)
 Prevention of thrombocytopenia-related haemorrhages
 RTP > 20% and/or CCI > 7
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• Platelet transfusion yield (PTY)
[PC after transfusion-PC before transfusion] X weight (kg) X 0.075
PTY =
Number of platelets transfused (X 1011)
PC: platelet count
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• Corrected Count Increment (CCI)
[PC after transfusion - PC before transfusion] X body surface area (m2) X 100
CCI=
Number of platelets transfused (X 1011)
PC: platelet count
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R = 0,9898
correlation CCI / PTY (365 valeurs)
correlation CCI/PTY (365 values)
R=0.9898
35
30
25
20
CCI
CCI
15
10
5
0
-0,6
-0,4
-0,2
0
0,2
0,4
-5
-10
-15
PTY
PTY
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0,6
0,8
1
1,2
Data EFS Bretagne
CHU Rennes
Oncohaematology
(Pr. Thierry Lamy)
Follow-up of the output of platelet transfusion
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Study of transfusion efficiency after
transfusions of single donor-apheresis
platelet concentrates and randomdonor platelet concentrates
J.VASSE, R.TARDIVEL, S.GAUCHERON,
G.ANDREU, G.SEMANA
June 2007
Page 24
RESULTS (1)
•
•
•
•
From 05/05/2005 to 09/04/2007
3496 platelet transfusions
2354 SD-APC
1141 RD-PC
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RESULTS (2)
Age of platelets
Total number
off SD-APC
delivered
Average yield
in %
Total number
of RD-PC
delivered
Average yield
in %
D1
221
32.07
79
29.13
D2
505
28.65
252
31.06
D3
607
28.42
246
27.10
D4
594
25.04
289
26.24
D5
427
25.36
275
24.43
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RESULTS (3)
Platelet count in
platelet
concentrates in
1011
Number of
SD-APC
delivered
Mean yield
in %
Number of
RD-PC
delivered
Mean yield
in %
3.5<5.5
735
25.82
969
26.97
>5.5
1324
29.79
20
27.67
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Distribution of the platelets transfused according to age
(N = 11207)
(08/02/2010-13/05/2012)
J1
J2
J3
J4
J5
3.3% 20.5% 28% 34% 14.2%
Distribution CPA/MCP
CPA: 41%
MCP: 59%
Page 28
Output and CCI according to the storage solution
presentation ISBT 2012 to come
CPA Plasma
CPA intersol
CPA SSP+
MCP SSP+
895
325
294
2167
29.75%
24.70%
29.29%
29.55%
3.9%
3.3%
3.2%
3.9%
10.23
8.65
10.01
10.32
45,2
41.6
40.2
47.2
manpower
average yield
variance of yield
average CCI
CCI variance
Page 29
Output according to the storage solution
presentation ISBT 2012 to come (4459 PC Transfusions)
CPA Plasma
CPA intersol
CPA SSP+
MCP SSP+
Manpower
923
519
453
2564
average yield
29,42%
23,8%
28,10%
28,6%
variance of yield
3.8%
3.3%
3.2%
3.9%
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Nbre
Receveurs
Rendement
Moyen
Variance du
rendement
CPA Intersol
519
23,79%
3,3%
CPA Plasma
923
29,42%
3,8%
CPA SSP+
453
28,10%
3,2%
MCP SSP+
2 564
28,60%
3,9%
 Tests de Comparaison des moyennes : utilisation du t de Student. La valeur de ce test
doit être supérieure à 1.96 pour accepter à 95% l’hypothèse selon laquelle les moyennes
observées sont différentes.
 Statistiquement, nous pouvons appliquer ce test de Student après avoir vérifié
l’homogénéité des variances. Le test de Fischer-Snedecor nous permet de valider cette
homogénéité car dans chacun des cas, le rapport de la variance la plus élevée sur la
variance la plus faible est inférieur à la valeur théorique de 1.57.
 Comparaisons des moyennes :
 CPA Intersol et CPA Plasma : F=1.15 et t=5.5  les moyennes sont différentes.
 CPA SSP+ et CPA Plasma : F=1.18 et t=1.2  les moyennes sont identiques.
 CPA SSP+ et MCP SSP+ : F=1.22 et t=0.5  les moyennes sont identiques.
 MCP SSP+ et CPA Plasma : F=1.03 et t=1.1  les moyennes sont identiques.
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type psl
CPA Intersol
CPA Plasma
CPA SSP+
MCP SSP+
Age du
P.S.L.
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5
Nbre
Receveurs
29
88
141
179
73
56
151
235
299
154
30
92
129
140
55
27
475
814
920
273
Rendement Variance du
t de Student
Moyen
rendement
28,5%
5,3%
25,5%
4,1%
0,6
23,6%
3,5%
0,7
23,6%
2,9%
0,0
21,6%
2,4%
0,9
32,3%
3,6%
29,4%
3,7%
1,0
28,9%
3,7%
0,3
31,4%
4,3%
1,5
24,8%
2,8%
3,7
32,6%
4,9%
29,4%
3,3%
0,7
28,9%
3,4%
0,2
26,4%
2,7%
1,2
25,7%
3,0%
0,2
33,9%
6,0%
30,4%
3,9%
0,7
29,0%
4,1%
1,2
27,4%
3,7%
1,7
27,7%
4,1%
0,2
La valeur du t de Student ici compare le
rendement moyen de l’âge du PSL sur la
ligne concernée avec la ligne juste au
dessus : ex : J5 vs J4
 En jaune, les moyennes significativement différentes :
J5 rendement moindre que J4 pour CPA Plasma
CPA/MCP SSP+ : les moyennes de rendement à 1 jour près peuvent sembler
décroître selon l’ancienneté du PSL, mais statistiquement ces moyennes
comparées au jour près sont identiques et ne présentent pas de différence.

Page 32
Results
4459 PC Transfusions
1219 Recipients
2264 yeld > 20% ( 60% PC Transfusions)
Page 33
Platelet transfusion
Inefficiency if output < 20% or CCI <7
Platelet concentrate
• Insufficient dose
• Altered platelets (transport, conservation… c.f. index of
spinning)
• Age of platelets
• Incompatible ABO
Patient
• Fever, CIVD, splenomegaly, drug
• Alloimmunisation HLA or HPA = refractory state
(polytransfused, graft,…)
Page 34
Platelet transfusion
Refractory state
Output < 20% or CCI < 7 on the results of the
count made 1 to 24 hrs after a second
transfusion of a concentrate of platelets:
• Compatible ABO
• Less than 48h of storage
• Having a sufficient quantity of platelets (0.5 *
1011/7kg)
Page 35
Antigenic systems and
alloimmunisation antiplatelets
Feverish and
allergic
reactions
Post-transfusional
thrombocytopenic
purpuras
Refractory states
poor outputs
System ABO
+
-
+
System HLA
++
?
+++
+++
+++
++
Systems HPA
Page 36
Causes of the refractory states to
platelet transfusions
Non alloimmune
Alloimmunes
Transfusional
•
•
Storage
Leucocytic contamination
•
•
•
.
•
Fever
splenomegaly
CIVD
MAT
CSH graft
Anti-HLA
•
•
Clinics
Anti-HPA
•
•
Unknown frequency, probably weak
Often not recognised
Anti-AB
Immunological
•
•
Frequent
Anti class I
•
Auto antibody
Immunoallergic antibodies
Page 37
Sometimes forgotten
Study TRAP
(Trial to Reduce Alloimmunization to Platelets Study
Group N. Eng. J. Med. 1997)


Co-operative study 530 LAM
4 groups of patients:
1.
2.
3.
4.
Transfused with pools of concentrates of normal
platelets
Transfused with pools of concentrates of platelets
treated with UV-B
Transfused with pools of concentrates of leucocytereduced platelets by filtration
Transfused with concentrates of platelets of apheresis
with leucocytes reduced by filtration
Page 38
TRAP study
(Trial to Reduce Alloimmunization to Platelets Study
Group N. Eng. J. Med. 1997)
Refractory state:
2
consecutive ineffective transfusions, CCI in the hour following
the transfusion < 5000/  L/m2
Compatible ABO
At least one of the two concentrates stored for less than 48 hrs.
Anti-HLA
MLCT
sensitized by an antiglobuline
60% cytotoxicity in 1 cell or 40% in 2
Tests prior to beginning of protocol and then every week for eight
weeks
Anti-HPA
Detection:
ELISA and flow cytometry
Confirmation: method of capture ELISA
Page 39
TRAP Study (NR. Eng.J.Med. 1997)
refractory states (RS) withtransfusions of platelets and
alloimmunisation
Temoins
131
UV-B 130
F-PC 137
F-AP 132
16%
10%
7%
8%
10 – 23%
6 –16%
4 –13%
4 –14%
32%
17%
10%
16%
21 – 47%
8 - 32%
4 – 22%
8 - 29%
45%
21%
18%
17%
36 –54%
15 – 30%
12 – 26%
12 – 26 %
Ac Anti platelets
11%
7%
6%
7%
RS
alloimmune
13%
5%
3%
4%
8 – 20%
2 – 11%
1 – 8%
1 – 9%
RS for all
patients
RS and
previous
pregnancies
Ac lympho
cytotoxic
Page 40
Risk factors of
alloimmunisation
Preliminary sensitizing
Previous
blood transfusions without leucocyte reduction
Prevopis
pregnancies 62% vs 33% of immunization
with/without leucocyte reduction (TRAP study)
Pilot
32% vs 10% of immunization with products
without leucocyte reduction vs products with leucocyte
reduction (TRAP study)
Page 41
Platelet transfusion
What to do in the event of a refractory state?
search for AC anti HLA /HPA
Search for compatible
platelets: phenotype CPA
compatibilized
cryostored
MCP
Page 42
Platelet transfusion
Other complications
Nonhemolytic
feverish reactions
Anti-erythrocyte alloimmunization (rhesus)
Allergy
Haemolytic accidents (haemolysins)
GVHD
Transmission of viruses, bacteria, parasitic infectious diseases
TRALI
Post-transfusional purpura
Page 43
Platelet transfusion
Prevention of complications
RFNH: fresh platelets,
deleucocytation, (deplasmatisation)
premedication of the recipient
Alloimmunization anti D:
Selection of platelets from Rh negative donor (protection
future obstétrical +++)+++)
Ig anti D
Passive anti D monitoring
Allergy:
Prefer additive platelets in solution to platelets in
plasma, (deplasmatisation?)
Page 44
Platelet transfusion
Haemolytic accidents (by AC immune ABO)
Detection of haemolysins
Respect Iso group if possible
Plasma removal
GVHD
Irradiation
Transmission of infectious diseases
Tracking of viruses: HBV, HCV, HIV, MVC
For the bacteria: medical maintenance, good
disinfection of the intake point, rules
of
hygiene, information post donation
Page 45
Platelet transfusion
Transmission of infectious diseases (continued)
For parasites: exclusion for donors when
returning
from endemic areas
Attenuation of pathogens: Amotosalen,
Riboflavin, UVC, but deterioration of the
platelet function involving of the
more frequent transfusions
Page 46
Platelet transfusion
TRALI
• Not-transfused male subjects
• Nulliparous women
• Multiparous negative ac anti HLA
Page 47
Post-transfusional purpura
Identification
Typical
form of brutal thrombocytopenia one week after the
transfusion of a blood product containing of the platelets
Atypical
form: refractory thrombocytopenia with the transfusions of
platelets
Diagnosis
In
addition to frequently present anti HLA, look for anti-HPA interest
of MAIPA with ac monoclonal suitable
Treatment
Generally
ineffective transfusion since PR associates an anti HPA
reaction automatically with an allo reaction
Plasma
exchange
IVIG
Page 48
Platelet transfusion
Conclusion
Two products with identical
effectiveness: CPA and MCP
Preserved in plasma or additive solution (PAS)
Able to use transformations or qualifications (phenotype, test
of compatibility, negative CMV) to adapt to the needs of the
patient
The selection, dose, and monitoring of platelet transfusions
must be subject to dialogue between the prescriber and the
transfusion centre
Page 49
Remerciements
Thanks
Pr. Jean-Yves Muller
Pr. Gilbert Semana
Dr.Georges Andreu
Dr.Julie Vasse
Mme Soline Gaucheron
Mr Jean-Pierre Lebaudy
Distribution team
Page 50