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THE STUBBORN PLATELET - REFRACTORINESS AT ITS WORST Dr. Anila Mathan, Consultant, Blood Bank & Hematology, SRM Institute of Medical Sciences , Chennai

The stubborn platelet - rEFRACTORINESS AT ITS WORST

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The stubborn platelet - rEFRACTORINESS AT ITS WORST. Dr. Anila Mathan, Consultant, Blood Bank & Hematology, SRM Institute of Medical Sciences , Chennai. Platelet transfusion refractoriness . Clinically suspected when patients do not respond as expected to the transfusion - PowerPoint PPT Presentation

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Page 1: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

THE STUBBORN PLATELET - REFRACTORINESS AT ITS WORST

Dr. Anila Mathan, Consultant, Blood Bank & Hematology, SRM Institute of Medical Sciences , Chennai

Page 2: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Platelet transfusion refractoriness Clinically suspected when patients do not respond as

expected to the transfusion Definition* :When 2 consecutive platelets

transfusions lead to a 1 hour post transfusion Corrected Count Increment (CCI) of less that 5000 platelets per m2 per µl.

Average expected increment 1 unit of random platelets 5000-10,000/cumm 1 unit of apheresis platelets 30,000-60,000/cumm

If pre & post transfusion platelet counts are not appropriately tested the diagnosis is unlikely to be made

*AABB 16th Edn

Page 3: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Guidelines for assessment of Platelet Refractoriness

Pre transfusion count to be done just prior to transfusion.

Post transfusion platelet count to be done1 hour & 18-24 hrs after transfusion to calculate Absolute Count Increment(ACI) or CCI.

The clinical response of the patient to the transfusion by cessation of bleeding is an important indicator for further tests.

Norms for our population are not yet established

Page 4: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Measure of Transfusion outcome

Formula Values s/o refractoriness

Absolute Count Increment (ACI)

(Post transfusion plt count – Pre transfusion plt count)

At 60 min ACI ,<5000/cumm after one unit of RDP

Corrected Count Increment (CCI)

(ACI x BSA m2)x1011

No. of plts transfused x 1011

At 10-60 min <5000/cumm

Posttransfusion Platelet Recovery (PPR)

ACI xTotal blood volume x100 No.of plts transfused

At 60 min <30%At 24hrs <20%(Normal at 1 hr: 67%)

AABB , Technical manual 16th Edn Pavenski et al, Tissue antigens 2012

BSA = Body surface area

Page 5: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

PLATELET REFRACTORINESS

HLA Class 1(80-90%)

Autoimmune

Human platelet antigen (10-

20%)

Alloimmune

Patient Related

Platelet Related

Immune Causes (20%)

Non Immune Causes (80%)

ABO incompatibility

HLA & HPA (rare)

Poor response to platelet transfusions

Drugs (Eg amphoterecin

B

Active bleeds Dilution by blood volume

Poor storage condition

DIC

Splenomegaly Number of units Tx

Fever , Sepsis Quality of platelets

Page 6: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Platelet Antigens

ABH

8 weeks Class1 , IgG

No dose response

HLA

HPA

Page 7: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Evaluation HLA Matching /Typing : Class 1 Screening for anti-HLA and anti-

platelet antibodies Antibody-mediated or not? Solid-phase

assay HLA antibody mediated or not? Panel

reactive antibody (PRA) as general screen for HLA Ab positivity. (20-30%)

Flow based assays :If positive, single antigen testing with microparticle beads to ID which antigen(s) to avoid in donors Luminex based single antigen bead assay C1q based SAB binding assay – better method for clinically relevant

HLA abs (Fontaine etal,2011)

Page 8: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Platelet crossmatching can used to check compatibility Platelet unit segment against patients serum

Solid-phase red cell adherence (SPRCA) test most widely used method

Disadvantage : Limited to units available for testing 5 day life to platelets, future transfusions will require

re-crossmatching Used in Europe and US as an alternative to HLA

matching Slichter SJ. Evidence-Based Platelet Transfusion Guidelines Hematology 2007

Page 9: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Prevention Non Immune

Blood Bank role Clinicians role

Immune ABO compatible HLA to ensure compatibility HPA

ABO compatibility Ensure donor recipient ABO compatibility Rate of platelet refractoriness is 69% in ABO

incompatible transfusions while in ABO compatible transfusion it is only 8%

Page 10: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Reduction of alloimmunisation

Decrease in alloimmunisation from 45% to 17-21% in previously unexposed patients – LR & UVB irradiation (TRAP study , NEJM 1997)

Universal prestorage leukoreduction incidence drop :Adopted in 19 countries

Prophylactic single donor plateletsOnly HLA matched pltsLeukoreduced plateletsIrradiated platelets

IVIG, Cyclosporin Plasmapheresis

Transfusion product

Recipient

Pavenski et al, Tissue antigens 2012

Page 11: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Management ABO matched platelet (<48 hrs old) HLA matching

Challenge in obtaining a well matched donor HLA typed donor registry Identify HLA antibody specificities and select antigen compatible

donors Degree of matching is important Cross reactive groups (CREGS) 2006 HLA matchmaker (software tool) - adequate CCI Recently 2010 epitope based matching PRA

Platelet cross matching Whatever the methodology for matching

Requires a large pool of dedicated typed donors No guarantee of a proper increment Not suitable for urgent requirements

Page 12: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Whatever the cause Cost of managing a refractory patient is very high

(Meehan et al Am J Hematol 2000 ;64:251-6)

How do we advice or manage a persistently refractory patient Small dose frequent platelet transfusion every 4-

8 hrs This maintains vascular integrity even if the CCI

does not increase IVIG Fibrinolytic inhibitors to stabilise any clots formed Recombinant factor VIIa to control bleeding

Slichter SJ. Evidence-Based Platelet Transfusion Guidelines Hematology 2007

Page 13: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Indian scenario Pubmed showed that studies have been

reported in 4 tertiary care centre The reports do not differ significantly

from studies in the west. However this a condition which we

need to keep in mind especially in patients requiring multiple transfusions.

Shastry S, Chaudahary R,Clinical factors influencing corrected count increment. Trans Ap Sc, 2012, Marwarha N,Sharma RR, Consensus and controversies in platelet transfusion.Trans Ap sc2009 41(2)Bajpai etal. Platelet alloimmunization in multitransfused patients with haemato-oncological disorders,Trans Ap Sc2012, Pandey p etal 2012 A prospective quality evaluation of single donor platelets (SDP) - an experience of a tertiary healthcare center in India., Chodhry VP Platlet therapy ,IJP 2002 69(9)

Page 14: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Conclusion Always suspect refractoriness if patients

symptoms or platelets counts don’t improve.

Try to ensure ABO compatibility . Universal Leukodepletion seems to be one

solution . Crossmatched compatible platelets seem to

be another. Cost effectiveness of all approaches to this

problem is a challenge.

Page 15: The stubborn platelet  - rEFRACTORINESS   AT ITS WORST

Communication, Coordination,Logistics are the key to the success of any enterprise including tackling the stubborn platelet Thank you

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Selection

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