2. Please comment on the following crossmatch report addressing
- The technique used (FCXM or CDC)
- The type of crossmatch (virtual or wet crossmatch)
- The advantages and disadvantages of the technique and the type of this crossmatch
- Will you go ahead based on this report?
- NB: This crossmatch is negative (authorised).
N
Dear All
I agree, it is a virtual crossmatch where we do not use CDC or FCXM.
What is the laboratory technique used in virtual crossmatch?
Dear Dr Ahmed,
The laboratory technique used in virtual crossmatch is the solid phase assay. The solid-phase assay can provide precisely the recipient and donor HLA tissue typing as well as the presence of any donor-specific DSA, which may attack the allograft if present in the recipient serum.
A computer system will analyze these data to virtually predict the crossmatch results if the lab actually mixed the recipient serum with the donor lymphocytes.
Solid phase assay
Solid phase assay used in VXM and because SPA is very sensitive and specific technique, the VXM is highly accurate
Virtual cross match uses single antigen bead technology to compare the unacceptable antigens of the recipient to the HLA typing of the donor(no need of donor lymphocytes) before an organ offer is made. so it can stratify the risk of transplantation
What is the technique?
technique is solid phase assay
Virtual crossmatch is based on the single bead technique, whereby the DSAs are identified and hence unacceptable antigens can be ascertained and compared against the HLA of the donor which is typed using molecular methods.
§ Virtual crossmatch involves a determination of the presence or absence of donor-specific HLA antibodies (DSA) in a patient by comparing the patient’s HLA antibody specificity profile to the HLA types of the proposed donor. ). Solid phase assay .
We can use it for non sensetize patients and with deceased donor it help to decrease the waiting time , the technique used is antigens coated beads technology or luminex
solid phase assay
Solid phase assay in virtual xm .
Dear All
The trap is in this sentence:
“The technique used (FCXM or CDC)”.
Also, you need to answer the rest of the questions of this scenario to get the price.
I can see many winners so far.
not CDC , not FCXM
it is virtual crossmatch VXM
advantages:
1- more link with transplant program
2-more link to know sensitized patients and and transplant them
3- help to reduce time to evaluate compatibility
disadvantages:
1- more time and work to allow the patient to understand more complicated information
2- also more time for the staff
3-more link with transplant program
4-negative test does not mean compatibility
but we can not depend on this report if there is history denoting sensitization, still we need to know DSA and to do FCXM
but if there is no history of sensitization , we can proceed for transplantation
NO CDC or FCXM is done, it is a virtual XM.
To proceed depending on virtual XM result only, the patient should be non sensitized, otherwise FCXM should be done in addition to virtual XM.
Advantages of virtual crossmatching:
Disadvantages of virtual crossmatching:
The technique used would be flowcytometry for detection of the fluorescent dye labelled bead coated with antigen to which the antibody binds. But it is not flowcytometry crossmatch (FCXM).
Virtual crossmatch
Advantage..
●Time/cost saving :
●more suitable for deceased doner as it filters patients in waiting list . Who are suitable for tx then transplant clinician select between them and go for fcxm or cDC .
Disadvantage
●false positive results due to sensitization or drug induced with rituximab as example .
●require high coordination between lab and tx clinician .
Dear All
This crossmatch is authorised (means negative).
As the virtual crossmatch is negative in this patient, if there is no history of sensitization, then the transplant can be performed in absence of a physical crossmatch.
Dear All
There is a trap in this scenario. I want you to think and read first before answering.
I can see good answers coming through, but still not complete. There is a present for the best answers (Kidney Transplant in Sensitised Patients). I will announce the winner on Saturday morning.
if there is a history of sensitization , we should do FCXM before but if there is no history of sensitization, we can proceed for transplantation depending on this report VXM
This reports shows HLA typing of both donor and recipient. No wet crossmatch was performed. A negative virtual crossmatch in a
patient with no known history of sensitization, for example: pregnancy, previous transplant or blood transfusion, VXM can be considered adequate to proceed with a deceased donor transplant without performing wet crossmatch. Otherwise, wet crossmatch-flow cytometry crossmatch is mandatory before transplantation.
Donor’s young age- 25 years and virtual crossmatch could indicate that the settings here is a deceased kidney donor. So in this context, proceeding with negative virtual crossmatch in the absence of sensitization is reasonable to minimize cold ischemia and avoid any unnecessary delays in laboratory.
If there is a history of sensitisation ( pregnancy, previous transplantation or blood transfusions),
FCXM is mandatory before transplantation
If FCXM positive , signify new DSA and need further evaluation before transplantation.
Blood groups : compatible
HLA mismatches:100
No PRA or sensitization history
This is a virtual cross match
I will not go for transplantation except if there is physical cross match FCXM and PRA
advantage of virtual crossmatch saving time, reduce the cold ischemia time. disadvantage: may give false positive with denatured HLA epitopes, weak DSA and allele-specific(non-DSA).
The technique used neither FCXM nor CDC it is single bead antigen technique by solid phase Assay
It is virtual cross matching its advantages are saving time and cost it is suitable for cadaveric transplant but disadvantage is false positive results
I will go ahead for transplantation based on this report it is 100 matching and no the DSAs
Not FXCM or CDC
It is virtual software method comparing Pt sera with donor Hal typing
Advantage of virtual cross match:
Increased sensitivity specially in high resolution epitope analysis
May be performed with stored sera so decreasing cold ischemia time
Improves risk assessment for rejection
Improves transplantation access in highly sensitized patients
Disadvantages :Can give false positive results
No I will not continue except after physical cross match
Virtual cross match is done using solid phase assay technique
*Technique used is neither FCXM nor CDC
*It is virtual XM, using Luminex Single Antigen Beads; no wet CM done
.It shows 100 mismatch with compatible ABO
Advantages: VXM decreases cold ischemia time in deceased donors , saves time, facilitates sharing donors offers, with more sensitivity than XM using serology. However, its disadvantages are related to inability to address non HLA ABs, and DSA intensity.
To use that VXM report correctly ,we need to know data of recipient history of solid phase anti HLA AB and history of sensitization for risk assessment .
also to proceed for FCXM
Dear All
Thank you very much
Yes, we use Solid Phase Assay (Luminex Single Antigen Beads), VXM is simply a paper crossmatch comparing the DSA specificity of the recipient against the HLA typing of the donor. Please email me to get your reward (email only)
This is a virtual crossmatch not FCXM or CDC-XM.
Virtual XM is based on donor’s HLA typing and Luminex single antigen assay to detect DSA. This technique is useful in sensitized recipients in whom a matched living donor, paired donor exchange (PDE) or compatible deceased donor are prefered options, respectively. In deceased donors it can reduce cold ischemic time and it makes finding the best recipient easier. But due to non-HLA antibodies, autoantibodies or sensitizing events after the last sampling, may be false negative virtual XM exist and it is better to at least perform CDC-XM before transplantation.
It’s virtual crossmatch test shows HLA typing of both donor and recipient with compatible ABO but 100mismatch advantages of this test is that it’s more sensitive to detect antibodies and eliminate false positive results from other tests so it helps to decrease waiting time and cost also help to improve cold time.
Disadvantages are false positive results due to detection of non complement fixing Ab and interference by IgM.
For this patient I need to know more information about his history for previous sensitisation if not sensitized and deceased donor we can do transplant without CDC or FCXM also we need to know about the degree of fluorescence whether it’s weak, moderate and strong .
If the patient has history of sensitisation or the transplantation will not done after the test immediately CDC and FCXM should be done to detect presence of DSA.
Neither FCXM or CDC, its solid phase assay
Virtual cross match
Advantages
Disadvantages
Yes I will go ahead, compatible blood group, 1-0-0 mistmatch, provided no new sensitizing events. the kidney transplantation can be safely performed without the need of a physical crossmatch as proven by multiple clinical trials that omit need for wet XM
solid phase technique SPI is specifc for HLA antibodies and thereby eliminates the false positives in CDC-XM and FCXM caused by non-HLA antibodies and autoantibodies. ELISA test is more sensitive than CDC-XM while the Luminex is more sensitive than both the CDC-XM and
FCXM.
HLA typing , virtual cross match .
Advantage : lead to improved cold time, similar rates of acute rejection, and potentially reduced delayed graft function rate. • More specific than serologic crossmatch • Less likely to deny access for a false positive physical crossmatch • Reduced cost • Does not preclude the performance of a physical XM; however, this may be completed concurrent with or after transplantation
.Disadvantage :Requires pt to understand more complicated information .positive cross match doesn’t guarantee compatibility .
We can depend on the report and go ahead for transplantation if the pt had no history sensitization .
*It’s neither CDC nor FCXM.
*It’s VXM of patient HLA antibody profile vs donor HLA typing .
*Advantage:
– decreased cold ischemia time .
– sensitive even to detect low titer antibody.
– decrease waiting time for ESRD patients especially highly sensitised patients.
*Disadvantage:
-false positive results due to denaturated antigens .-require more consuling patient to accept any complications.
– good coordination between lab and transplantation staff mandatory.
* I will go ahead with this result ,
-ABO compatible .
-HLA 100 mismatch.
-VXM negative .
* this accepted in deceased donor but in living donor Must FCXM to be done first.
This is a virtual Cross match, neither a flow cytometry nor CDC ( both are types of wet cross matches )
This technique in VCM is solid phase assays ( Luminex Single bead )
Advantages of VCM :
Safe and quick method for donor selection
Decrease cold ischemia time
Decreases waiting time of ESRD patients
Disadvantages of VCM , it may give false negative results which may be due to non tested Abs ( against C , DQ , DP , non HLA )
Technique used is;
luminex –SAB.
Type of cross match is ;
virtual cross match.
Advantages of virtual cross match;
-Luminex-SAB assay has enabled accurate screening of prospective recipients for
DSA without an actual ‘wet’ crossmatch based on donor and recipient serum sampling.
– It has also eliminated the need for mandatory pre-transplant physical crossmatch and improved organ allocation efficiency based on such pre-identified UA.
-it decreases the waiting time for transplantation ,specially in highy sensitized recipient .
It decrease the cold ischemia time .
Disadvantages of virtual cross match ;
-false result ; A positive VXM with a negative FCXM, could be due to low titre antibodies of doubtful clinical significance and is often considered safe to proceed with transplantation . – A negative VXM in the presence of a FCXM+ result may signify the presence of‘new’ DSA and needs further evaluation before transplant. Similarly, the implications of a positive VXM .
-The result of VXM is also dependent on the time of DSA screening and can vary depending on which sample of serum was used for testing.
Will you go ahead based on this report ?
ABO matched pairs .
HLA 100 .
Negative virtual cross match
-It is important to know ,if there is history of sensitization ?
-Although the virtual cross match is negative ,it is mandatory to do anew
FCMX immediately before transplantation to detect any recent antibodies .
If there is no history of sensitization and the FCMX in negative ,we can go ahead based on this report .which showed a low immunological risk .we can proceed without induction using triple TAC .
Reference ;
Bielmann D, Hönger G, Lutz D, et al. (2007) Pretransplant
risk assessment in renal allograft recipients using virtual
crossmatching. Am J Transplant 7: 626-632.
Tambur AR, Ramon DS, Kaufman DB, et al. (2009) Perception versus reality?: Virtual crossmatch–how to overcome. some of the technical and logistic limitations. Am J Transplant 29: 1886-1893
The technique used not FCXM nor CDC.its virtual cross match in which we just compare patient’s Ab to donor tissue typing to detect DSA( solid phase crossmatch)
The advantages
1)Facilitate matching across large geographic area.
2)very sensitive test(specially by luminex) which can detect very low titre Ab
3)no need to mix patient serum with donor lymphocytes so it save time which finally will safe organ by decreasing cold ischemia time.
disadvantages
1) expensive and need experienced clinical pathologist
2) can detect non complement fixing Ab which may result in unnecessary rejection of acceptable donor
3) complicated to be explained to the patient
4)if positive..the cutoff to reject or accept may be ambiguous
5)it only screen for antibodies so not the whole immune system.
Will you go ahead based on this report?
In cadaveric transplant..Yes I will proceed to safe time and organ
In living transplantation…i would prefer to do flow cytometry crossmatch to more convenient of absence of any DSA even non HLA ones
First, DNA-based molecular crossmatch has been done for the donor and recipient. Although this recipient and the donor are 100 mismatched, it doesn’t exclude the need to utilize concise and sensitive techniques to screen for DSA such as SAB. Then, in-silico computer-based virtual crossmatch has been performed between HLA type of donor and recipients’ anti-HLA antibody screening results.
Some important tips:
-HLA-typing should be comprehensive, requiring information regarding all HLA loci (HLA-A, -B, -C, DRB3/4/5, DQA1/DQB1, and DPA1/DPB1) in both donor and recipient.
-HLA-typing should be performed using molecular methods and, at least when determination of DSA is required, antigens with more than one allele common in the donor population should be assessed at high resolution.
-HLA antibody assessment should be performed by solid phase assays and should include information regarding all major HLA loci (HLA-A, -B, -C, DRB3/4/5, DQA1/DQB1, and DPA1/DPB1), if possible, antibody information should be captured at the allele level.
The advantages of VXM:
Improving the overall transplant ability in sensitized patients
It has eliminated the need for mandatory pre-transplant physical crossmatch, improving organ allocation efficiency based on preidentified unacceptable antigens.
Leads to shortening cold ischemia time.
Improves risk assessment for rejection
The disadvantage of VXM:
-There are false positive and false negative results for VXM
False positive result:
-False-positive SAB test (no “true” DSA) due to:
-False-negative SAB:
-Detection of a low burden of DSAs that are not important for graft survival may result in unnecessary non-acceptance of kidney allograft and the patient stay on the waiting list for a longer time.
-Sometimes true” anti-HLA antibody is present in the recipient sera but goes undetected in the SAB assay (false-negative result). For example, the presence of IgM antibody after recent exposure to unacceptable anti HLA antigens before IgG formation.
Some important tips:
-The absence of pretransplant DSAs does not imply a lack of prior sensitization, as testing reflects only the antibody levels present in the serum sample being tested.
-Careful examination of longitudinal SAB screening and prior crossmatching results may reveal the presence of a historical DSA and immunologic memory against the donor antigen.
-Some studies have shown that sensitized recipients (with non-DSA alloantibody) are at higher risk for graft failure.
-Acceptable antigens (in contrast to unacceptable HLA antigens) does not mean that there is no immune memory or no HLA antibody specific for acceptable antigen. In many instances, it is because a DSA is below the program’s risk threshold.
-Lack of donor HLA loci typing does not equal absence of a DSA directed to that HLA loci.
-Currently, classification of patients as “sensitized” or “naïve” is strongly influenced by the most recent circulating HLA antibody test – percent PRA and specific HLA antibody identification. While this information is beneficial to predict lymphocyte crossmatch results, it does not provide complete and accurate information regarding the patient’s sensitization history and his or her likelihood to have a recall memory response against the transplanted organ. Specifically, patients with 0% PRA in a current serum sample may have had historic HLA antibodies after a sensitizing event that may or may not be apparent to the clinician based on availability of sera and frequency and length of historic HLA antibody testing.
-The result of VXM also depends on the time of DSA screening. Most recent assays may not detect DSA from past exposure that may be associated with graft loss. On the other hand, VXM with historical DSA may miss new antibodies.
-Latent potential for an alloimmune memory response: One or more of:
• A history of a sensitizing event
• Non-DSA HLA antibody detected at one or more time points prior to transplant
• Non-DSA HLA antibody detected at the time of transplant.
-An accurate patient history must be obtained consist of HLA sensitization events:
Pregnancy, transfusion, previous transplant, implants (VADs)
Inflammatory events that may boost pre-existing alloimmune memory:
Major surgeries, major infections, recent vaccinations.
In this scenario, the patient with negative VXM, if has no recent history of sensitization such as blood transfusion, and pregnancy can proceed with donor transplantation, but if there is a positive history, a FCXM is mandatory before transplantation and a positive result may show a new DSA formation.
High-resolution epitope analysis VXM not wet as it’s not using mixture of cells and serum to detect cell lysis
Advantages if VXM
Decrease cold ischemia time
Allows better selection of patients out f waiting list
Improves allocation of the graft
Better chances for sensitized patients
Disadvantages
Sensitization history of the patient must be considered
Loss of some epitope may occur
Cannot exclude Non HLA-AB
High sensitivity which can exclude a potential donor
Require coordination between lab and transplantation team
Denatured human leucocyte antigens on single antigen beads may lead to a false positive result.
Will you go ahead based on this report?
The pair is ABO compatible.
And this VXM IS negative
In this case HLA mismatches is 100.
Final XM must be done befor proceeding and must check DSAs.
VXM can be enough to proceed with a deceased donor transplant without performing wet crossmatch to decrease cold ischemia time
Provided that no history of sensitization.
In living donor crossmatch-flow cytometry crossmatch is mandatory before transplantation with the fact that antibodies vary with times and we needs FCXM, cPRA &SAB with final crossmatch before proceeding to transplantation.
virtual crossmatch VXM show HLA typing
between
donor and recipient done by using DNA-based molecular technique.
not FCXM or CDC
The report show ABO combatablity between donor and recipient with HLA mismatch 100
Mismatch at A (HLA locus)
Addvantage
virtual crossmatch is highly accurate.
reduced testing costs and, cold ischemia time by reducing uncertainty and the time needed for testing after the organ arrives at the transplant center
virtual crossmatch accuracy has facilitated kidney paired donation (KPD) programs
Disadvantage
Denatured human leucocyte antigens on single antigen beads may lead to a false positive result
Cannot recognize the presense of non HLA Abs
Requires more coordination between immunology lab personnel and transplant team
In our practice we will do the
CDC, flow cytometry, DSA titer if all these parameters are negative we will preceed for kidney transplantation without desensitization regem
Reference
1-Callus R .Basic concepts in kidney transplant immunology .HMED_2017_78_1_32_37.indd 32.
2-Gabriel M. Danovitch, MD. Handbook of Kidney Transplantation. SIXTH EDITION
It is neither a flow nor a CDC but it I is a virtual cross match comparing HLA typing of the donor and recipient based DNA molecular technology.
It is a virtual cross match
Advantages:
Eliminates the physical cross match
Reduces cold ischemia time
Reduces laboratory workload
Add a precision to actual cross match (CDC if MFI > 15000 and FCXM if MFI > 5000)and DSA identification
Improves allocation efficiency
Increase rate of transplantation for sensitized donors
The risk of memory response can be accounted eg: previous Transplantation and blood transfusion
Disadvantages
Denaturated antigens, epitope loss
Cannot exclude Non HLA-AB or autoantibodies
High sensitivity which can exclude a potential donor
In this scenario there is no mentioned history of sensitization(like pregnancy or blood transfusion), HLA match is 100. However we need to check for DSA
If negative DSA… proceed with this virtual cross match
positive DSA MFI >1000 but with well-defined stable AB …. proceed with virtual cross match
But if MFI> 2000 with unstable AB, allele specific AB, DP α or DQ α or too many week AB we will need to proceed with a final wet physical FCXM cross match
The technique used is molecular HLA typing , it is not FXCM nor CDC.
The pair is ABO compatible with 100 mismatch , the virtual crossmatch was negative . The cross match here was virtual not wet crossmatch , its advantages are ,decrease cold ischemia time , rapid allocation of D.D among sensitized patients and improve allocation efficacy ,and decrease the lab works .Its disadvantages are, no information about presence of DSA, sensitization& its degree .In this report the sample has to be within 3-6 months, due to the virtual cross match might gives a false positive result ( antibodies vary with times & affected by sensitization) .So with the above data if the sample was fresh we can proceed for cadaveric transplant as long as HLA A locus is insignificant , while for living pair needs FCXM, cPRA &SAB with final crossmatch before proceeding to transplantation.
The report state that t is VXM (virtual crossmatch) and it is written that it is 1 mismatch
we can see that the mismatch is HLA*01:03 against 01/32. so it is in the specific allele.
It seems safe to go ahead with this transplant but it seems a diseased donor so we need to deal with this as high risk because of probable cold ischemia and risk of delayed graft function etc.
I prefer to perform final crossmatch if possible
this virtual crossmatch is based on solid-phase assays mainly based on flow cytometry technique (Luminex etc.)
the advantage of virtual crossmatch is its ability to detect more specşfically the present antibodies and help choose the most appropriate recipient more specifically
The technique used is FCXM
The type of cross match is a virtual cross match of a deceased doner ( a serial number was given )
Advantages
· Avoiding potential incompatible organs
· In deceased donor transplants it has reduced the number of tests which has resulted in improvement of organ allocation and reduction of waiting and ischemia time .
· The living donor evaluation became faster , faster decisions for desensitization and easy paired doners allocations
Disadvantages
There is no universally agreed upon cut-off for an unacceptable MFI or SFI for the antibodies
Denatured antigens on the beads
The type of this cross match is Single bead antigen assays
Will you go ahead based on this report? Yes as long as the recipient had not any sensitization event after provision of his serum.
Virtual Crossmatch (VXM)
It describes the profile of the recipient’s HLA against the donor’s HLA.
VXM helps in organ allocation, so decreasing waiting time for transplantation especially for the highly sensitized recipient, decreases ischemia time, it predicts the result of physical crossmatch.
In the case of DD, can precede, with this VXM if there is no H/O sensitization.
If there is H/O sensitization, we need to do FCXM before transplantation.
-Donor and recipient blood groups are A +ve Rh, so they are compatible.
-It is a virtual crossmatch which is a software or computer program that assesses immunological compatibility by comparing HLA typing of both donor and recipient -HLA typing is done by DNA-based typing technique(sequence-specific oligomer). It is high-resolution typing (give classification at alleles)
-It is not CDC or FXCM.
-Donor and recipient HLA is compatible with 100 mismatches.
–Advantage of virtual crossmatch:
-less time is needed for the evaluation of compatibility.
-reduce cold ischemia time
-Facilitates matching over a larger geographic area and the transplantation of more highly sensitized patients.
-reduce cost.
-Improve risk assessment for rejection.
– Disadvantage of virtual crossmatch:
-Negative crossmatch does not guarantee compatibility
-Require more coordination with the transplant team.
-This patient has a negative VXM, so he needs full assessment(history esp for sensitization and clinical examination) if no history of sensitization proceeds with a deceased donor transplant without wet crossmatch. If the patient has a history of sensitization(pregnancy, blood transfusion, or previous transplant)aFCXM is mandatory before transplantation. If FCXM +means presence of new DSA and further evaluation before transplant.
Nalaka Gunawansa, Roshni Rathore, Ajay Sharma and Ahmed Halawa .Crossmatch Strategies in Renal Transplantation: A Practical Guide for the Practicing Clinician Journal of Transplant Surgery.October 25, 2017
It is virtual cross match
100 mismatch
not CDC nor FXM
Type of cross match is virtual cross match
Advantages:
Save time
Decrease ischemia time
Allows for detection of highly sensitized patients
Improve allocation program
Disadvantage:
Can not detect DSA and non HLA AB
I will not proceed for transplantation in this case and I need to do wet cross match ,FXM and luminax.
-The used technique is a HLA molecular typing( solid phase assay)
-virtual crossmatch
-It’s advantage is that it can be done with stored sera so can be practical for cadaveric donors so it aids in detecting rapidly the suitable donor as well as being more sensitive and specific thereby reducing the cold ischemia time without increasing rejection or graft survival risk and of great benefit for those exchanging organs in distant locations also it provided an access to highly sensitised patients
It’s disadvantage is that denaturated HLA on a bead can give false positive results also it needs collaboration between transplanting team and cross matching laboratory
-its validity depends on the recipient’s historic and potentially sensitizing events as well as sera used for virtual cross matching if collected more than30 days is considered acceptable for unsensitized patients ,current and historic DSA need to be considered
So in this case if this patient isnot highly sensitised with a recent sample and negative solid phase and negative virtual cross matching we can proceed with the transplantation
This is a report of virtual cross match comparing HLA typing of both donor and recipient done by DNA-based molecular technique. It is not FCXM or CDC
Despite the good immunological status as ( ABO combatable , HLA mismatch 100, no DSA)
But still I wouldnot proceed to transplantation based soly on this cross match . Our centre protocol is to perform a wet cross match CDC initial and final FCXM.
As negative virtual crossmatch cannot exclude presence of non HLA Abs , autoantibodies as well as the dynamic state of DSA that change over time However , we can proceed with transplantation without further cross match , if it was a deceased donor to minimize cold ischemia time .
Advantages of virtual cross match
1- Decrease number of patients need to under go wet crossmatch
2- Decrease cold ischemia time in cadaveric kidney transplantation
Disadvantage
1- Cannot exclude presense of non HLA Abs, autoantibodies
2- Cannot assess DSA intensity or its immunological risk
3- Cannot assess the change in DSA level over time .
Well done
It is a molecular HLA typing with virtual cross matching revealed one mismatch in locus A. virtual cross matching provide the advantage of reducing cold ischemia time however it may provide false positive results due to interaction with denaturated epitopes.
although, this virtual cross match is negative and can predict the physical cross match, but wet cross match is needed before transplantation
ABO compatible
No CDC or FCXM
This is virtual crossmatch (VXM) , assume for localization of
compatible DD .100mismatch.
mention date of authoraziation only, what about the date of sample collection ?
VXM referred to the detection of unacceptable antigens in otherward
compares the recipient’s UA against the HLA screening of the potential
donor, by computer based virtual matching assay rather than an actual
wet’ cross match.
Missing the c PRA in this report
History of sensitization?
-the advantage with the VXM that is help in rapid allocation of compatible DD for sensitized recipients with less cold ischemic time and shorting the waiting list for
transplantation ,
If negative VXM with no previous history of sensitization will go
ahead with DD TX if this is fresh sample as the DSA
profile can be changed with in time especially in sensitized
patients due to the effect of memory cells .
In case of sensitization history even negative VXM will ask
for FCXM, IF negative VXM with positive FCXM this indicated
the presence of new DSA, which need further quantification prior
to proceed with transplantation
If positive VXM with negative FCXM may still indicate the
presence of low titer DSA that may not clinically relevant and still
can proceed with the transplantation.
This repot not enough to decide further about the acceptance for
DD transplantation .
Thank you Dr. Saja
It is Allocation NOT Localization
From this report, do you think there is a previous sensitizing event?
If you are obliged to accept this offer, would you go for a physical XM while the patient is in the OR?
Sorry for spelling mistakes if this test done on stored sera from the recpient and more than 3 months , (the date of sample collection not mentionin the above report )so in that case yes i should consider the possiblity of sensitazation and i will ask for repeat aphysicalXM if this VXM done in fesh sample and for allocation of DD we can proceed with transplantaion with out the need forrepat physical XR as one of the advantages of VXM is to reduce CIT ( Cold ischemia time and reduce risk of DGF (1).
reference:
1-Virtual Crossmatching in Kidney Transplantation: The Wait Is Over
Vinayak S Rohan 1, Nicole Pilch 1, Omar Moussa 1, Satish N Nadig 1, Derek Dubay 1, Prabhakar K Baliga 1, David J Taber 2
J Am Coll Surg 2020 Apr;230(4):373-379.
From above info realise that it is abo matched cadaveric renal transplant
100 mismatch
If we can have single antigen class one and two reports would be useful
As I am into living door program am not confident to proceed for transplant based on this report
Thankyou Vijayarajakumar the tissue typing and matching are the same for LD and DD
but in LD there is the luxurry of having an initial cross match FCXM and a final one in almost all cases .
Vijay
This an excellent match. I agree with Prof Belal below. Please think about it and get back to us. I’m sure you will get it right
Molecular based HLA typing in a virtual crossmatch
Solid phase immunoassay would identify HLA antibodies of known specificities in patient’s serum and enable determination of virtual crossmatch.
advantages of virtual crossmatch:
no need for physical presence of donor cells
allow detecting match options when several potential living donors are considered (1)
improve outcome and increase rate of transplant in sensitized recipient (2)
improve allocation efficiency (2)
decrease lab. work as it identify unacceptable antigens based on solid phase immunoassay and crossmatch results so decrease number of unexpected crossmatch (3)
Disadvantages:
presence or absence of antibodies and their specificity may vary with time and may be influenced with pregnancy, blood transfusion or transplants, so should consider serum within <3-6 months. (4)
false positive results due to low titer or complement binding antibodies may mistakenly exclude compatible donors. (4)
false negative results due to prozone effect and potential HLA antigens not in standard panel of solid phase immunoassay (5)
Several studies showed that virtual crossmatch including single antigen bead testing can predict physical cross match and transplantation can be performed safely without increase in risk of rejection and with the benefit of decreased cold ischemia time. (6,7)
Other studies showed that physical crossmatch should be performed with the virtual cross match and the impact of inaccurate virtual crossmatch shouldn’t be underestimated (5,8)
(1) Lonze, Bonnie E. “Histocompatibility and management of the highly sensitized kidney transplant candidate.” Current opinion in organ transplantation 22, no. 4 (2017): 415-420.
(2) Althaf, Mohammed Mahdi, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, and Ahmed Mostafa Halawa. “Human leukocyte antigen typing and crossmatch: A comprehensive review.” World journal of transplantation 7, no. 6 (2017): 339.
(3) Kamoun, M., et al., HLA compatibility assessment and management of highly sensitized patients under the new kidney allocation system (KAS): A 2016 status report from twelve HLA laboratories across the U.S. Hum Immunol, 2017. 78(1): p. 19-23.
(4) Tinckam KJ. Basic histocompatibility testing methods. In: Chandraker A, editor. Core concepts in renal transplantation. New York: Springer Science+Business Media, LLC, 2012: 21-42
(5) V. Jani et al., Root cause analysis of limitations of virtual crossmatch for kidney allocation to highly-sensitized patients, Hum. Immunol. (2016).
(6) Rohan, V.S., Pilch, N., Moussa, O., Nadig, S.N., Dubay, D., Baliga, P.K. and Taber, D.J., 2020. Virtual crossmatching in kidney transplantation: the wait is over. Journal of the American College of Surgeons, 230(4), pp.373-379.
(7) . Turner D, Battle R, Akbarzad-Yousefi A, Little AM. The omission of the “wet” pre transplant crossmatch in renal transplant centres in Scotland. HLA 2019;94:3e10
(8) ] D.E. Stewart, A.Y. Kucheryavaya, D.K. Klassen, N.A. Turgeon, R.N. Formica, M.I. Aeder, Changes in deceased donor kidney transplantation one year after KAS implementation, Am. J. Transplant. 16 (2016) 1834–1847
prudent reply thankyou Heba.
This pair is Abo compatible, the report showed HLA typing , (HLA A 03) 100 mismatch.
No FCXM nor CDC crossmatch was done .The virtual cross match report was not complete.
Although ,this pair is ABO compatible and 100mismatch (HLA A03), the data mentioned in the report is not enough to proceed for transplantation, pending history of sensitization ,antibody screening for the recipient with its titer ,cPRA, FCXM for T & B, with all pending tests we can do the virtual crossmatching which is valid & enough to proceed for transplantation if it is negative.
Have a look at the report again; check for sensitization history. Any Suggestion?
1-No flow\CDC cross-match done, he is authorized for virtual crossmatch.
HLA typing was done using the DNA based molecular technique. the advantages of the technique detect the difference at the level of the allele, and this will increase the accuracy and sensitivity of the test. (HLA mismatch 1:0:0)
2-virtual crossmatch
3-advantage of virtual crossmatch saving time, reduce the cold ischemia time. disadvantage: may give false positive with denatured HLA epitopes, weak DSA and allele-specific(non-DSA).
4- I will not proceed with transplantation based on that report, without a physical or virtual crossmatch.
Type and technique of cross match
Virtual cross match using sequence specific oligomer (SSO) Luminex for HLA typing of both donor and recipient to asses HLA matching between recipient and most probably deceased donor.
Advantages of HLA typing is to asses HLA matching which is strongly associated with graft survival.
Disadvantages : it doesn’t give us information about the presence of DSA, degree of sensitization of the recipient.
Result of cross match
⦁ Donor and recipient are ABO compatible
⦁ Donor and recipient are HLA compatible with 100 mismatch
⦁ No data about sensitization of the recipient
⦁ No data about the presence or abcense of clinically significant DSA
Will you go ahead based on this report?
Yes … i will proceed but after the following :
1. Assessment of cPRA using Luminex assay
2. Assessment of DSA using Luminex and compare it with HLA profile of recipient
3. Performing a final pretransplant wet cross match between donor and recipient
Then proceed in transplantation according to the risk stratification
A- highest risk = transplantation is contraindicated
⦁ Positive CDC
⦁ Positive FCM with MCS> 250
⦁ Positive DSA with RIS 17 or more
B- Very high risk = require desensitization, induction using alemtuzumab and IVIG, maintenance using triple therapy, fu protocol
⦁ Positive FCM with MCS of 250 or less
⦁ Positive DSA with RIS < 17
C- High risk= possible desensitization, induction mandatory using ATG, maintenance using triple therapy, fu protocol
negative cross match +
⦁ 6 antigen mismatch or
⦁ Retransplantation or
⦁ cPRA> 80 %
D- Intermediate risk = induction using ATG or basiliximab, maintenance triple therapy, follow up
Negative cross match +
⦁ 4-5 antigen mismatch or
⦁ Retransplantation or
⦁ cPRA 20- 80 %
E- low risk= induction therapy using basiliximab, maintenance triple therapy, fu
lack all above
F- lowest risk = HLA identical 000 mismatch
So … if no DSA, cross match is negative and cPRA< 20 % proceed to transplantation as low risk using induction by baseliximab and triple iimmunosupressive regimens
Moreover, we have to be sure that recipient and donor are suitable for transplantation
Thank you for your explicit report for your conditional approval to go for a TX?
This a virtual cross match done for a recipient who had a donor with compatible blood group;it should be a real time FCXM, also PRA by luminex should be done for DSA. They didn’t mention the sample time and the test done by some one rather than authorised one .
Advantage of virtual cross match is shorting the waiting list for transplant and the disadvantage it is not a real cross match for T and B lymphocytes for the specific donor with his recipient.
No I will not proceed till did the FCXM
Thankyou for high lighting generally for the dates between the VXM and the wet XM.
-The mentioned scenario is ABO blood group matching: Which is matching both donor and recipient are A positive.
-HLA matching between donor and recipient which revealed :100 at HLA -A, HLA- B and HLA -DR (one mismatch in one locus at HLA-A.
-Patient is candidate for virtual crossmatch (VXM)
-Technique of HLA matching is DNA-based HLA typing using molecular techniques: Has a more sensitivity, accuracy and resolving power than serologic typing methods, Sequencing-based typing (SBT) is a high-resolution method for the identification of HLA polymorphisms. There is split antigens in the mentioned scenario.
–Will you go ahead based on this report?
Basically, it is a good HLA matching but the decision for transplantation will depend on crossmatching between donor and recipient and presence and percentage of DSA.
The technique used (FCXM or CDC)
The type of crossmatch (virtual or wet crossmatch)
The advantages and disadvantages of the technique and the type of this crossmatch
Will you go ahead based on this report?
Good
Virtual cross matching.
This 100mismatch result in HLA locus. 0 1 1.
No FCXM OR CDC CXM to determine sensitization of the patient.
Advantage:
Increased sensitivity
May be performed with stored sera therefore shortening cold ischaemia time
Improves transplantation access for highly sensitized patients
Improves risk assessment for rejection.
Disadvantage:
Denatured human leucocyte antigens on single antigen
beads may lead to a false positive result
Requires more coordination between immunology lab personnel and transplant team
it is virtual crossmatch
we should do DSA percent PRA
we cannot proceed except after doing T and B cell cross match
adv
1- more link with transplant program
2-more link to know sensitized patients and transplant them
3- help to reduce time to evaluate compatibility
disadv.
1- more time and work to allow the patient to understand more complicated informations
2- also more time for the staff
3-more link with transplant program
4-negative test doesnot mean compatibility
This report is not a crossmatch report. It summarizes the HLA typing of the prospective transplant recipient and prospective donor (deceased). The report suggests a 100 mismatch.
Type of crossmatch requested is virtual crossmatch (VXM) for which the Solid phase immunoassay of the recipient is required, which is missing in the information provided.
In this report, a virtual cross match (VXM) is requested.
A virtual crossmatch (VXM) is a form of crossmatch in which no physical crossmatch is done and the unacceptable antigens for the recipient are matched against the HLA of the prospective organ donor.
The advantage of a VXM is that it saves time and rapid allocation of organ to prospective donor on the basis of unacceptable antigens derived by analysing the solid phase immunoassay report of the stored/ historical serum of the prospective recipient. It helps in reducing cold ischemia time.
The disadvantage of a VXM is that as it is based on historical data, if a new sensitizing event happens later, the antibodies can be missed leading to a false negative VXM. Similarly, if a later solid phase immunoassay shows absence of DSA previously detected and a VXM is negative, transplanting the kidney can still lead to antibody mediated rejection due to the memory cells.
Hence it is important to perform a VXM with all the previous DSA reports and hence a flowcytometry cross match should be performed even with a negative VXM.
The crossmatch report is missing in the data provided.
The history of sensitization will be important in this patient.
Assuming the virtual crossmatch is negative in this patient, if there is no history of sensitization, then the transplant can be performed in absence of a physical crossmatch.
Assuming the virtual crossmatch is negative in this patient, and there is history of sensitization, a flowcytometry cross match should be done and if it is negative, then the transplant can be performed.
Reference:
Gunawansa N, Rathore R, Sharma A, et al. Crossmatch strategies in renal transplantation: A practical guide for the practicing clinician. J Transplant Surg 2017;1:8-15.
Is the time lapse between the recipient serum (if stored) and the donor,s HLA antigens of any significance?
Sure with time passing he can become sensitized for whatever the cause like blood transfusion, infection etc,so it is mandatory to repeat the cross match every 3 months.
Yes. If the stored serum is old, there might be new sensitization events post the time of taking that serum sample and hence newer antibodies might be present in the recipient. Hence it is important to have a newer serum sample for assessing unacceptable antigens of the recipient.
Excellent response, to the point
Virtual cross match between ABO compatible donor & recipient, 100 mismatch, no DSA result available. Advantages of VXM include:
Disadvantages of VXM include:
This patient need assessment for DSA, if no DSA the patient can precede for transplantation depending on VXM with out need for FCXM.
Ideally if feasible I would still do a CDC cross match if the donor cells are viable and transport is feasible considering the cold ischemia time. There are various studies published about the utility of the virtual cross match as a replacement to CDC cross match and have found to be non inferior to CDC in terms of delayed graft function and short term graft survival.
The donor and recipient are Abo compatible( both have A blood group).
They have only one HLA mismatch (HLA A 03) 100 mismatch.
No flow cytometry crossmatch nor CDC crossmatch is done .
The donor and recipient virtual crossmatch is requested but the results had not been written.
Even if the result of virtual crossmatch is negative we need final physical crossmatch ( CDC XM or flow crossmatch).
Donor and Recipient are ABO-Compatible, as both having group A-Rh positive (no ABO incompatiblity).
Regarding HLA matching between Donor and Recipient ; there’s only one mismatch at a locus in HLA-A
The technique used in this tissue typing was FCXM and VXM( Virtual XMatch based on beads technology)
The value of positive FCXM lies in using it for cross matching of sensitized patients who have an inherently higher risk of acute graft rejection to determine transplant feasibility or need for desensitization protocols prior to transplant.
Advantages and Disadvantages of using technique :
Flow cytometry
Advantages:
Disadvantages:
Solid phase assays (ELISA and bead technology)
Advantages:
Disadvantages:
I will proceed in the transplantation process for this patient providing the followings:
wise decision but still the question is:
would you accept transplanting this patient only with a negative virtual crossmatch and no FCXM despite the ABO cmpatibility and the 100 mismatch.
-This is a FCXM virtual technique.
-there is 100 mismatch in HLA -A
this a report of cross match between donor and recipent with the same blood group, A .
the donor and recpient HLA cross match ,1:0:0 mismatch .
they used The Luminex Single-Antigen Beads (LSA) vitrual cross match.
virtual cross match protocol showed high sensitivity in predicting donor-recipient immunologic compatibility
vritual cross match negative results showed good correlation with both CDC and FC a-XMs (97% and 90%, respectively). The sensitivity of v-XM was 100%; this high value was related to the lack of false-negative DSA results. The limited specificity with both techniques (CDC-XM, 74%; FC-XM, 79%) was due to the presence of “acceptable” and/or anti-DQA/DPB DSA in some patient sera used to perform the a-XMs.
advantages of virtual cross match
1-deceresing number of pt needs actula cross match
2-decers time requried for final cross match
3-mimnimize wated time cross matching highly sensitized recpient, with know incomaptibilties
4-deceresing clod ischemia time
disadavantges of vritual cross match
1-antibody profile can change by time
2-desntization protocols can cause real time variation in antibody profile
3-may elimnate an eligble recipent on local perefence(patient with antibody 50% on the A2 cells on the panel)
sure i will go ahead for this kidney transplantion considering the pt low immnological risk .
1-e-ISSN 1643-3750 © Med Sci Monit, 2019; 25: 952-961 DOI: 10.12659/MSM.914902
2-ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
ABO compatible pair ( blood group A ) with 100 mismatch.
Crossmatch technique is virtual crossmatch based on the HLA typing( by DNA based molecular method) of the patient and the donor, there is a need for luminex testing to detect the recipient’s antibodies and the presence of DSA. Negative virtual XM in a patient with no history of sensitization is considered adequate to proceed for transplantation but in sensitized patients, flow cytometry crossmatch is mandatory before transplantation.
Advantages of virtual crossmatching:
Disadvantages of virtual crossmatching:
advantage of flow crossmatch technique:
Disadvantage of flow crossmatch technique:
can not differentiate between HLA and non-HLA antibodies.
The cross match is between ABO compatible donor and recipient with 100 mismatch. In this clinical scenario the crossmatch is virtual, based on the availability of HLA typing results of both donor and recipient, but not recipients DSA.
HLA typing was done using DNA-based molecular technique, as we see in this report, showing typing at split level.
Virtual crossmatch is not enough to proceed with transplantation as VXM could be negative when other crossmatch studies (CDC or FXM) are positive. For example the presence of non-HLA antibodies or IgM antibodies or antibodies against particular loci that are not routinely reported by HLA laboratory cause a negative virtual crossmatch with positive CDC technique.
Based on this report only we can proceed with the transplantation as we do not know if the recipient is sensitized so we need to screen the recipient for donor specific antibodies and perform flowcytometry cross match.
Reference:
-Lectures by ASNRT STAFF
-Uptodate
***Based on this report only we can NOT* proceed with the transplantation as we do not know if the recipient is sensitized so we need to screen the recipient for donor specific antibodies and perform flowcytometry cross match.
This reports shows HLA typing of both donor and recipient. No wet crossmatch was performed. A negative virtual crossmatch in a
patient with no known history of sensitization, for example: pregnancy, previous transplant or blood transfusion, VXM can be considered adequate to proceed with a deceased donor transplant without performing wet crossmatch. Otherwise, wet crossmatch-flow cytometry crossmatch is mandatory before transplantation.
Donor’s young age- 25 years and virtual crossmatch could indicate that the settings here is a deceased kidney donor. So in this context, proceeding with negative virtual crossmatch in the absence of sensitization is reasonable to minimize cold ischemia and avoid any unnecessary delays in laboratory.
The technique used (FCXM or CDC)
This seems like an incomplete virtual cross match report .It has the HLA typing mentioned of the donor or the recipient but no mention of the Luminex SAB assay report of the recipient telling about the presence of any DSA against HLA A31 and if present then the MFI of the antibody against HLA A 31.Also knowing the point of the Luminex SAB assay with respect to the transplantations and if any previous historical Luminex SAB assay of the recipient available would be better.
The type of crossmatch (virtual or wet crossmatch)
Type is virtual cross match, gaining importance in deceased donor transplant.
The advantages and disadvantages of the technique and the type of this crossmatch
advantages
Less time needed for evaluation of compatibility
results in more efficient use of the system
Reduced cold ischemia time
Facilitates matching over larger geographic area, renal paired donations, and the transplantation of more highly sensitized patients
Can result in improved access for sensitized patients
Increased sensitivity and specificity of testing can lead to a better matched donor/recipient
More specific than serologic crossmatch-(includes patient history, etc)
Less likely to deny access for a false positive physical crossmatch
Does not preclude the performance of a physical XM; however, this may be completed concurrent with or after transplantation
Fewer unexpectedly positive physical crossmatches leads to more efficient use of transplant personnel
Improved risk assessment for rejection
Allows for optimized immunosuppression and desensitization protocols
Disadvantages
Based on the program’s criteria for crossmatches, there is potential to deny use of a donor organ that could be successfully transplanted
Requires patient to receive and understand more complicated information Negative crossmatch (physical or virtual) does not guarantee compatibility.
Program staff have to learn a new interpretive vocabulary
Additional time and work to ensure that patients understand their risk and get all the information on time.
Will you go ahead based on this report?
Since CDC and FCX negative will go ahead.
CDC positive – avoid
CDC negative ,FCXM positive
If DSA is negative in recipient(Luminex report needed) will go ahead.
If DSA is positive but MFI<1000- will go ahead.
If DSA is positive and MFI>1000-avoid
Correction
CDC and FCXM negative
If DSA is negative in recipient(Luminex report needed) will go ahead with basiliximab induction.
If DSA is positive but MFI<1000- will go ahead with ATG induction.
If DSA is positive and MFI>1000-avoid
CDC positive – avoid
CDC negative ,FCXM positive
If DSA is negative in recipient(Luminex report needed) will go ahead ATG induction.
If DSA is positive but MFI<1000- will go ahead with ATG induction.
If DSA is positive and MFI>1000-avoid