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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
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
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
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
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
Platelet Antigens
ABH
8 weeks Class1 , IgG
No dose response
HLA
HPA
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)
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
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%
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
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
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
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)
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.
Communication, Coordination,Logistics are the key to the success of any enterprise including tackling the stubborn platelet Thank you
Selection