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Helen North
HLA Selected Platelets
Dr Helen North PhDClinical Scientist
Department of Histocompatibility & ImmunogeneticsNHS Blood and Transplant Colindale
Helen North
Poor increment (<10 x 109/L or CCI <7.5 ) after at least two consecutive transfusions of random donor platelets
Platelet count taken from one hour to 24hours post transfusion.2011 NHSBT recognised count could be taken after 10 minutes
Helen North
Platelet Refractoriness
Causes:
immunological and non-immunological
Helen North
Old/poorly stored platelets, small doseSplenomegaly, hepatomegalyDIC (infection, septicaemia, malignancy)Infection (CMV)FeverAntibiotics, amphotericin B, ambisome, vancomycin, ciprofloxacin,
Helen North
Immunological causesPreformed antibodies in recipient to antigens on
platelets:
HLA - class I specific antibodies (HLA-A,-B)Most common cause of immune refractoriness
Rarely HLA -C
HPA antibodies (HPA-1a, -2b etc)Incompatibility for HPA is uncommon
ABO - antibodiesIncompatible platelets transfused into patients with high titre anti-A or anti-B have a decreased survival
Helen North
removal from circulation
phagocytosis
SPLEENpatient antibodies
transfused platelets
Y
Y
Y
YYYY
Y YY
complement and Immunoglobulin Fc Receptors
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Transfusion with non leucodepleted bloodHistory of pregnancy Multiple transfusions
Seftel et al 2004; Blood 103(1) : 333-339
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Role of H&I laboratoryInvestigate for immune refractoriness
Identify the HLA and HPA antibody specificity HLA (HPA) typing of patients
Maintain a panel of HLA and HPA typed donors Select and issue HLA compatible platelets for immune refractory patientsEssential to evaluate post-transfusion incrementsAdvice on patient management
Helen North
Laboratory tests prior to provision of HLA selected platelets
HLA class I typing 1x 6ml EDTA anti-coagulated sample
HLA-A, B,C type (HLA class I type)
using PCR-SSP or luminex SSO technology
Antigen level of typing
HLA antibody identification1x 6ml clotted serum sample
Luminex technology to identify antibody specificity
Helen North
Provision of HLA Selected Platelets (HSP)
The provision of HSP is based on the patient s:-
HLA typeHLA class I antibody specificity.
If present, HPA and ABO antibody specificity
If requested, CMV and RhD status is taken into consideration.
Helen North
Alleles Antigens
HLA-A 1,729 28
HLA-B 2,329 61
HLA-C 1,291 10
Jan 2012
To provide the best matched unit:- Require at least 24 hours notice for routine orders of HLA selected platelets
Helen North
HLA selected plateletsApheresis collection from a single donor
Platelet count >240x109/doseLeucocyte depleted Leucocyte count <5x106/doseIrradiated
Known HLA and HPA genotype
In a stable patient the expected increment after 1 dose = 30-40 x 109/L
Helen North
The donor and patient are matched at the antigen level of the HLA-A and B loci.
Patient A*01,A*02; B*08,B*44
Donor 1 A*01,A*02; B*08,B*44
Donor 2* A*01,A*01; B*08,B*08
*homozygous donor
Helen North
B match grades (B1 B2 B3 B4)Anywhere from one to four mismatched HLA antigens (HLA-A and/or B loci) are transfused into the patient.
Avoid mismatched antigen(s) to which the patient has antibodies againstideally the mismatched antigen(s) will be similar to the patient s HLA antigens (reduces risk of further sensitisation).
Patient s type: HLA-A1,A2;B8,B44Donor s type: HLA-A1,A68*;B8,B44 (B1 match)* = cross-reactive with HLA-A2
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Helen North
Availability of HLA selected platelets
14,000 typed platelet apheresis donors Currently ~80% of platelet stock are from apheresis donors Patients with common HLA types
a good chance of finding a well matched platelet from the daily platelet stock
Helen North
2013 - HLA selected platelet units
In 2013:15,783 HLA selected platelets issued by NHSBT 8,773 issued to London and SE region (55.6%)
Tooting and Colindale H&I lab
75% A and B1 match grade units (Colindale 2013)
Helen North
Value of increments to NHSBTTo ensure that NHSBT is providing selected platelets that are beneficialPatients are reviewed weeklyIf post transfusion increments are poor (<10x109):
Investigate further cause of poor increments
presence of anti-HPA or ABO antibodies.Patients actively being transfused:
Monitor their antibody profile monthlyEnsure no further sensitisation
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For difficult to match patients:Not all HLA antibodies cause refractorinessIdentify acceptable mismatches
Currently only receive 50% of increments from hospitals
Varies greatly between hospitals
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Current clinical trial:Epitope matched HLA selected platelets
Currently HSP are matched based on antigens However, antibodies bind to epitopesHLAMatchmaker (Duquesnoy) identifies epletswithin antigens thought to represent epitopes
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3rd choice
2nd choice
1st choice
G052514302071N (19 Eplet)
G072414175858* B2 Grade (1 Eplet)
G072414175973U (17 Eplet)
G072414175973U A Grade (17 Eplet)
G072414175858*(1 Eplet)
G052514302071N A Grade (19 Eplet)
Eplet match and priorityCurrent match grade and priority
Data from Collette Pigden
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Increase the number of acceptable mismatched units
Without further sensitisation
Possibly increase our knowledge of acceptable mismatchingStill recruiting patients to enrol in the trial
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Case 1: Platelet refractoriness due to HLA antibodies
Patient:: 54 yr old male, diagnosis: MyelodysplasiaReferred to H&I Colindale:
Poor response to ABO compatible pooled and single donor platelets
HLA type HLA-A*30, A*32; B*18, B*35HLA antibodies detected:
All HLA-A locus antigens except A30 and A32B7 CREG antigens (B7,27,40,42,48,54,55,56,73,81)Also B8,B44,B45,B57,B58
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Case 1Due to the patient's antibody profile:
predicted not to increment with over 90% of random plateletsPre transfusion count: 13 x 109/LPost transfusion count on random platelets: 18 x 109/L
Helen North
Case 1: Increments following HLA selected platelets
Patient's HLA type is A30,A32;B18,B35A match grade HLA selected platelets
incremented from 16 to 43 x109/LHowever, only 5 A matched donors available in the UK
B2 match grade HLA selected plateletsA32,X;B14,B52 incremented from 24 to 43 x109/L
Helen North
Patient management
Patient with MDS requires lifelong platelet supportAs an outpatient, requires two HLA selected platelet units/week
to maintain an adequate platelet count. As only a small selection of donors are suitable
Search for suitably matched donors (A, B1,B2 match) and arrange for them to be bled to meet expected requests.Difficult to manage this patient at short notice