PLATELET TRANSFUSION IN ONCOHAEMATOLOGY Dr.René TARDIVEL Etablissement Français du Sang 9 th Maghreb Haematology Conference Sousse 25-26 May 2012

PLATELET TRANSFUSION

IN ONCOHAEMATOLOGY

Dr.René TARDIVELEtablissement Français du Sang

9th Maghreb Haematology Conference

Sousse 25-26 May 2012

Page 2

Indications for platelet transfusion

Central thrombocytopenia together with treatment of the cause

Thrombopathy, occasional

Peripheral thrombocytopenia, exceptional

Page 3

Platelet concentrates (1)

APC RPP

Origin Cell separatorsFrom total blood

CLP or BC

Composition 1 donation 4 to 6 donations

Quantity of platelets in 1011 2 to 8 3 to 5

Volume/ml 200-400 or more 200-350

Principal characteristics

Page 4


APC RPP

Separators•Haemonetics MCS ++•Terumo BCT Trima•Fenwal Amicus•Fresinus Comtec

Several program options by separators

2 products:• PRP• CLP or BC

2 techniques:• manual• automatic-Orbisac-TACSI

Principal characteristics

Page 5


Storage5 days (7 days in certain countries in the event of bacterial detection or attenuation of pathogens)Continuous agitation20-24 °Cconcentration: 1.2-1.5.106/mm3 (recommendations)

Page 6


APC RPP

Leukocyte reduction + +

Stored solution + +

Irradiation + +

Plasma removal + +

Reduction of volume + +

Viral attenuation + +

Paediatric preparation ++/-

Mixtures of 2 units

Cryoconservation + -

Possible transformations

Page 7


APC RPP

Negative CMV + +

Phenotype HLA, HPA + -

Compatibility test + -

Possible qualifications

Page 8


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

Page 9

Platelet transfusion indication

Preventive or curative?

Page 10

Platelet transfusion indication (1)

Curative

Patient presenting a haemorrhage

Page 11

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,…)

Page 12

Platelet transfusion - PreventiveDose (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 - 1453Klumpp TR and coll: Clinical consequences of alterations in platelet transfusion dose: prospective, randomized, double-blind trial transfusion 1999; 39:674 - 681Sensebe 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

Page 13


However, other studies show that a low dose 2-3 1011 can also be effectiveTinmouth 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

Page 14


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 bleedingsNo significant difference when with the number of days before appearance of grade 2 bleeding or higher, no matter what the dose

Page 15

Platelet transfusion - Preventivetransfusional thresholds (1)

Pietersz R.N.I International Forum –Prophylactic platelet transfusion – Vox Sanguins 2012

14 responses by different countries

In the absence of risk factor10.109/l (except Russia and in certain indications from Japan

and the Netherlands: 5-109/l

Page 16


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

Page 17


Other situations

Invasive techniques: catheter, implantable chamber, fibroscopy, biopsy, broncho-alveolar washingSurgery, severe haemorrhage ,DIVC,…

Threshold raised to 50.109/l or above

Page 18

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)

Page 19

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

Page 20

• 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

Page 21

• 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

Page 22

correlation CCI / PTY (365 valeurs)

-15

-10

-5

0

5

10

15

20

25

30

35

-0,6 -0,4 -0,2 0 0,2 0,4 0,6 0,8 1 1,2

PTY

CCI

R = 0,9898

R=0.9898 correlation CCI/PTY (365 values)

PTY

Page 23

Data EFS BretagneCHU Rennes

Oncohaematology(Pr. Thierry Lamy)

Follow-up of the output of platelet transfusion

Page 24

Study of transfusion efficiency after transfusions of single donor-apheresis platelet concentrates

and random-donor platelet concentrates

J.VASSE, R.TARDIVEL, S.GAUCHERON, G.ANDREU,

G.SEMANAJune 2007

Page 25

RESULTS (1)

• From 05/05/2005 to 09/04/2007• 3496 platelet transfusions• 2354 SD-APC • 1141 RD-PC

Page 26

RESULTS (2)Age of

plateletsTotal 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

Page 27

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

Page 28

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/MCPCPA: 41%MCP: 59%

Page 29

Output and CCI according to the storage solution

presentation ISBT 2012 to come

CPA Plasma CPA intersol CPA SSP+ MCP SSP+

manpower895 325 294 2167

average yield29.75% 24.70% 29.29% 29.55%

variance of yield3.9% 3.3% 3.2% 3.9%

average CCI10.23 8.65 10.01 10.32

CCI variance 45,2 41.6 40.2 47.2

Page 30

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%

Page 31

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.

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%

Page 32

En jaune, les moyennes significativement différentes : J5 rendement moindre que J4 pour CPA PlasmaCPA/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.

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

type pslAge du P.S.L.

Nbre Receveurs

Rendement Moyen

Variance du rendement

t de Student

1 29 28,5% 5,3%2 88 25,5% 4,1% 0,6 3 141 23,6% 3,5% 0,7 4 179 23,6% 2,9% 0,0 5 73 21,6% 2,4% 0,9 1 56 32,3% 3,6%2 151 29,4% 3,7% 1,0 3 235 28,9% 3,7% 0,3 4 299 31,4% 4,3% 1,5 5 154 24,8% 2,8% 3,7 1 30 32,6% 4,9%2 92 29,4% 3,3% 0,7 3 129 28,9% 3,4% 0,2 4 140 26,4% 2,7% 1,2 5 55 25,7% 3,0% 0,2 1 27 33,9% 6,0%2 475 30,4% 3,9% 0,7 3 814 29,0% 4,1% 1,2 4 920 27,4% 3,7% 1,7 5 273 27,7% 4,1% 0,2

CPA Intersol

CPA Plasma

CPA SSP+

MCP SSP+

Page 33

Results

4459 PC Transfusions

1219 Recipients

2264 yeld > 20% ( 60% PC Transfusions)

Page 34


Inefficiency if output < 20% or CCI <7Platelet 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 35


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 36

Antigenic systems and Antigenic systems and alloimmunisation antiplateletsalloimmunisation antiplatelets

Feverish and Feverish and allergic allergic

reactionsreactions

Post-Post-transfusional transfusional

thrombocytopenthrombocytopenic purpurasic purpuras

Refractory Refractory states poor states poor

outputsoutputs

System ABOSystem ABO ++ -- ++

System HLASystem HLA ++++ ?? ++++++

Systems HPASystems HPA ++++++ ++++++ ++++

Page 37

Causes of the refractory states Causes of the refractory states to platelet transfusions to platelet transfusions

Non alloimmuneNon alloimmuneTransfusional

• Storage• Leucocytic contamination

Clinics• Fever• splenomegaly• CIVD. MAT• CSH graft

ImmunologicalImmunological• Auto antibodyAuto antibody• Immunoallergic antibodiesImmunoallergic antibodies

AlloimmunesAlloimmunes

Anti-HLAAnti-HLA• FrequentFrequent• Anti class IAnti class I

Anti-HPAAnti-HPA• Unknown frequency, probably weak Unknown frequency, probably weak • Often not recognisedOften not recognised

Anti-ABAnti-AB• Sometimes forgottenSometimes forgotten

Page 38

Study TRAP Study TRAP (Trial to Reduce Alloimmunization to Platelets (Trial to Reduce Alloimmunization to Platelets

Study Group N. Eng. J. Med. 1997)Study Group N. Eng. J. Med. 1997)

Co-operative study 530 LAMCo-operative study 530 LAM 4 groups of patients:4 groups of patients:

1.1. Transfused with pools of concentrates of normal Transfused with pools of concentrates of normal plateletsplatelets

2.2. Transfused with pools of concentrates of Transfused with pools of concentrates of platelets treated with UV-Bplatelets treated with UV-B

3.3. Transfused with pools of concentrates of Transfused with pools of concentrates of leucocyte-reduced platelets by filtrationleucocyte-reduced platelets by filtration

4.4. Transfused with concentrates of platelets of Transfused with concentrates of platelets of apheresis with leucocytes reduced by filtrationapheresis with leucocytes reduced by filtration

Page 39

TRAP studyTRAP study (Trial to Reduce Alloimmunization to Platelets (Trial to Reduce Alloimmunization to Platelets

Study Group N. Eng. J. Med. 1997)Study Group N. Eng. J. Med. 1997)

Refractory state:Refractory state:2 consecutive ineffective transfusions,2 consecutive ineffective transfusions, CCI in the hour CCI in the hour following the transfusion < 5000/ following the transfusion < 5000/ L/m L/m22

Compatible ABOCompatible ABOAt least one of the two concentrates stored for less than 48 At least one of the two concentrates stored for less than 48 hrs.hrs.

Anti-HLA Anti-HLA MLCT sensitized by an antiglobulineMLCT sensitized by an antiglobuline60% cytotoxicity in 1 cell or 40% in 260% cytotoxicity in 1 cell or 40% in 2Tests prior to beginning of protocol and then every week for Tests prior to beginning of protocol and then every week for eight weekseight weeks

Anti-HPAAnti-HPADetection: ELISA and flow cytometryDetection: ELISA and flow cytometryConfirmation: method of capture ELISAConfirmation: method of capture ELISA

Page 40

TRAP StudyTRAP Study (NR. Eng.J.Med. 1997)refractory states (RS) withtransfusions of platelets

and alloimmunisationTemoins Temoins

131131UV-B 130UV-B 130 F-PC 137F-PC 137 F-AP 132F-AP 132

RS for all RS for all patientspatients

16%16%10 – 23%

10%10%6 –16%

7%7%4 –13%

8%8%4 –14%

RS and RS and previous previous pregnanciepregnanciess

32%32%21 – 47%

17%17%8 - 32%

10%10%4 – 22%

16%16%8 - 29%

Ac lymphoAc lympho

cytotoxiccytotoxic45%45%

36 –54%21%21%

15 – 30%18%18%

12 – 26%17%17%

12 – 26 %

Ac Anti -Ac Anti -plateletsplatelets

11%11% 7%7% 6%6% 7%7%

RSRS

alloimmunealloimmune13%13%

8 – 20%

5%5%2 – 11%

3%3%1 – 8%

4%4%1 – 9%

Page 41

Risk factors of Risk factors of alloimmunisationalloimmunisation

Preliminary sensitizingPreliminary sensitizingPrevious blood transfusions without leucocyte Previous blood transfusions without leucocyte reductionreductionPrevopis pregnancies 62% vs 33% of Prevopis pregnancies 62% vs 33% of immunization with/without leucocyte reduction immunization with/without leucocyte reduction (TRAP study)(TRAP study)

Pilot 32% vs 10% of immunization with products Pilot 32% vs 10% of immunization with products without leucocyte reduction vs products with without leucocyte reduction vs products with leucocyte reduction leucocyte reduction (TRAP study)(TRAP study)

Page 42


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 43


Other complications

Nonhemolytic feverish reactionsAnti-erythrocyte alloimmunization (rhesus)AllergyHaemolytic accidents (haemolysins)GVHDTransmission of viruses, bacteria, parasitic infectious diseasesTRALIPost-transfusional purpura

Page 44

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 45


Haemolytic accidents (by AC immune ABO)Detection of haemolysinsRespect Iso group if possiblePlasma removal

GVHDIrradiation

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 46


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 47


TRALI

• Not-transfused male subjects• Nulliparous women• Multiparous negative ac anti HLA

Page 48

Post-transfusional purpuraPost-transfusional purpura

IdentificationIdentificationTypical form of brutal thrombocytopenia one week after the Typical form of brutal thrombocytopenia one week after the transfusion of a blood product containing of the plateletstransfusion of a blood product containing of the plateletsAtypical form: refractory thrombocytopenia with the Atypical form: refractory thrombocytopenia with the transfusions of plateletstransfusions of platelets

DiagnosisDiagnosisIn addition to frequently present anti HLA, look for anti-HPA In addition to frequently present anti HLA, look for anti-HPA interest of MAIPA with ac monoclonal suitableinterest of MAIPA with ac monoclonal suitable

TreatmentTreatmentGenerally ineffective transfusion since PR associates an anti Generally ineffective transfusion since PR associates an anti HPA reaction automatically with an allo reaction HPA reaction automatically with an allo reaction Plasma exchangePlasma exchangeIVIGIVIG

Page 49


Conclusion

Two products with identical effectiveness: CPA and MCPPreserved 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 patientThe selection, dose, and monitoring of platelet transfusions must be subject to dialogue between the prescriber and the transfusion centre

Page 50

RemerciementsThanks

Pr. Jean-Yves MullerPr. Gilbert SemanaDr.Georges AndreuDr.Julie VasseMme Soline GaucheronMr Jean-Pierre LebaudyDistribution team

Documents

PLATELET TRANSFUSION IN ONCOHAEMATOLOGY Dr.René TARDIVEL Etablissement Français du Sang 9 th Maghreb Haematology Conference Sousse 25-26 May 2012