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Dr.René TARDIVEL Etablissement Français du Sang. PLATELET TRANSFUSION IN ONCOHAEMATOLOGY. 9 th Maghreb Haematology Conference Sousse 25-26 May 2012. Indications for platelet transfusion. Central thrombocytopenia together with treatment of the cause Thrombopathy, occasional

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Dr ren tardivel etablissement fran ais du sang

Dr.René TARDIVEL

Etablissement Français du Sang

PLATELET TRANSFUSION IN ONCOHAEMATOLOGY

9th Maghreb Haematology Conference

Sousse 25-26 May 2012


Indications for platelet transfusion

Indications for platelet transfusion

  • Central thrombocytopenia together with treatment of the cause

  • Thrombopathy, occasional

  • Peripheral thrombocytopenia, exceptional


Platelet concentrates 1

Platelet concentrates (1)

Principal characteristics


Platelet concentrates 2

Platelet concentrates (2)

Principal characteristics


Platelet concentrates 3

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)


Platelet concentrates 4

Platelet concentrates (4)

Possible transformations


Platelet concentrates 5

Platelet concentrates (5)

Possible qualifications


Platelet concentrates 6

Platelet concentrates (6)

CPA or MCP

  • No difference in effectiveness

  • No difference in frequency of immunization

  • No product superior to another, but one may be better adapted to the patient


Platelet transfusion indication

Platelet transfusion indication

Preventive or curative?


Platelet transfusion indication 1

Platelet transfusion indication (1)

Curative

  • Patient presenting a haemorrhage


Platelet transfusion indication 2

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,…)


Platelet transfusion preventive dose 1

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 - 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


Platelet transfusion preventive dose 2

Platelet transfusion - PreventiveDose (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


Platelet transfusion preventive dose 3

Platelet transfusion - PreventiveDose (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


Platelet transfusion preventive transfusional thresholds 1

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 factor

    10.109/l (except Russia and in certain indications from Japan and the Netherlands: 5-109/l


Platelet transfusion preventive transfusional thresholds 2

Platelet transfusion - Preventivetransfusional 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


Platelet transfusion preventive transfusional thresholds 3

Platelet transfusion - Preventivetransfusional thresholds (3)

  • Other situations

    Invasive techniques: catheter, implantable chamber, fibroscopy, biopsy, broncho-alveolar washing

    Surgery, severe haemorrhage, CIVD,…

    Threshold raised to 50.109/l or above


Platelet transfusion dose in practice

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)


Platelet transfusion

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


Platelet transfusion in oncohaematology

  • 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


Platelet transfusion in oncohaematology

  • 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


Platelet transfusion in oncohaematology

R=0.9898correlation CCI/PTY (365 values)

CCI

PTY


Platelet transfusion in oncohaematology

Data EFS Bretagne

CHU Rennes

Oncohaematology

(Pr. Thierry Lamy)

Follow-up of the output of platelet transfusion


Platelet transfusion in oncohaematology

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.SEMANA

June 2007


Platelet transfusion in oncohaematology

RESULTS (1)

  • From 05/05/2005 to 09/04/2007

  • 3496 platelet transfusions

  • 2354 SD-APC

  • 1141 RD-PC


Platelet transfusion in oncohaematology

RESULTS (2)


Platelet transfusion in oncohaematology

RESULTS (3)


Platelet transfusion in oncohaematology

Distribution of the plates 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%


Platelet transfusion in oncohaematology

  • 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.


Platelet transfusion in oncohaematology

  • 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.

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


Results

Results

  • 4459 PC Transfusions

  • 1219 Recipients

  • 2264 yeld > 20% ( 60% PC Transfusions)


Platelet transfusion1

Platelet transfusion

Inefficiency if output < 20% or CCI <7

  • Platelet concentrate

    • Insufficient dose

    • Altered platelets (transport, conservation… c.f. index of spinning)

    • Plaquettes proches date de péremption

    • Incompatible ABO

  • Patient

    • Fever, CIVD, splenomegaly, drug

    • Alloimmunisation HLA or HPA = refractory state (polytransfused, multipair)


Platelet transfusion2

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)


Antigenic systems and alloimmunisation antiplatelets

Antigenic systems and alloimmunisation antiplatelets


Causes of the refractory states to platelet transfusions

Non alloimmune

Transfusional

Storage

Leucocytic contamination

Clinics

Fever

splenomegaly

CIVD

. MAT

CSH graft

Immunological

Auto antibody

Immunoallergic antibodies

Alloimmunes

Anti-HLA

Frequent

Anti class I

Anti-HPA

Unknown frequency, probably weak

Often not recognised

Anti-AB

Sometimes forgotten

Causes of the refractory states to platelet transfusions


Study trap trial to reduce alloimmunization to platelets study group n eng j med 1997

Study TRAP (Trial to Reduce Alloimmunization to Platelets Study Group N. Eng. J. Med. 1997)

  • Co-operative study 530 LAM

  • 4 groups of patients:

    • 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 leucocyte-reduced platelets by filtration

    • Transfused with concentrates of platelets of apheresis with leucocytes reduced by filtration


Trap study trial to reduce alloimmunization to platelets study group n eng j med 1997

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


Platelet transfusion in oncohaematology

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


Risk factors of alloimmunisation

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)


Platelet transfusion3

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


Platelet transfusion4

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


Platelet transfusion5

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?)


Platelet transfusion6

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


Platelet transfusion7

Platelet transfusion

Transmission of infectious diseases (continued)

For parasites: forty donors when returning from endemic areas

Attenuation of pathogens: Amotosalen, Riboflavin, UVC, but deterioration of the platelet function involving of the more frequent transfusions


Platelet transfusion8

Platelet transfusion

  • TRALI

    • Not-transfused male subjects

    • Nulliparous women

    • Multiparous negative ac anti HLA


Post transfusional purpura

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 transplant

    • IVIG


Platelet transfusion9

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


Remerciements thanks

RemerciementsThanks

  • Pr. Jean-Yves Muller

  • Dr.Julie Vasse

  • Mme Soline Gaucheron

  • Mr Jean-Pierre Lebaudy

  • Distribution team


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