ElinF

MTP and Emergency release is a verbal phone call to the blood bank with a signed form during the event.  Routines need an order faxed from the provider or orders placed into Epic.  Happy New Year! 

MTP and Emergency release is a verbal phone call to the blood bank with a signed form during the event.  Routines need an order faxed from the provider or orders placed into Epic.  Happy New Year! 

I could "listen" to Malcolm explain stuff all day!!  

So our sister lab was cited last week (September 2022) by TJC for not QCing panel cells. That lab had at one time been a branch of a reference lab so of course they never QC'ed panel cells for reasons given above.  We are arguing back that it is a procedural QC process that we would never do a panel if the screen was negative.  So if they don't react when they expect them to then we do other processes.  (ie repeat, check for gel junk/misc reactivity in the screen, run it on tube, etc).  Our lab does QC our panels on receipt (because a TJC surveyor told us to years back) to make sure they are reactive, but we currently do not Qc them every day of use.  And the IFU now states that we need to look at our "regional and national guidance, standards, regulations and professional preferences. and Each lab must develop specific procedures..."  All AABB states is to have a QC policy that works basically.  
I told our manager to ask them exactly what they want.  (I am sure every surveyor will be different, and  we may just have to satisfy them with the smoke and mirrors QC unfortunately.)

A few of our newer employees state that their previous employers had required this, but I had never heard of this.  We were trained by our ortho rep back in 2005 or so to pipette straight up and down for both reagent cells and plasma.  My question is since many labs are automated for blood bank now, how do the analyzers pipette the samples.  Is there an air gap in the testing with the Provue or the Vision? 

This sound like what we are doing...You are now my best friend  so we can trade tips and secrets!  haha

Blood products that were taken into isolation are never returned to us.    If they are not used, they are discarded in the room.

I could "listen" to Malcolm explain stuff all day!!  

I could "listen" to Malcolm explain stuff all day!!  

This is amazing and most definitely deserved!!  I love reading your responses to EVERYONE'S questions and your knowledge is unbelievable.  Thank you for all your help! 

We have also used the small Helmer incubator. It was very dependable over a lot of years. We have since upgraded to the next larger size.

We have the i Series Helmer incubator and have had no problems 

Interestingly enough, I was at a conference recently where forum threads from Bloodbanktalk were used as source material and included as part of the lecture.

Interesting patient #2 this month.  A multiple myeloma patient who had no history had all testing positive in Gel, including the  Auto control.  Expecting a Warm auto we sent the specimen to the reference lab.  Again, they sent it further to the American red Cross.  They discovered a new medication on the med list was a medication that pretty much interfered with all blood bank testing except Immediate spin crossmatches.    Darzalex is the name of the drug.  The bulletin is below from the AABB.   So, while the patients are on this drug, our reference lab will have to perform the antibody screens for us. 
 
 
 
Association Bulletin #16-02
Date: January 15, 2016
To: AABB Members
From: Donna M. Regan, MT(ASCP)SBB—President
Miriam A. Markowitz—Chief Executive Officer
Re: Mitigating the Anti-CD38 Interference with Serologic Testing
Summary
A new class of therapeutic agents for multiple myeloma, CD38 monoclonal antibodies, can result in interference with blood bank serologic tests and thereby cause delays in issuing Red Blood Cell (RBC) units to patients receiving these agents. To minimize these delays, hospitals should set up procedures to inform the transfusion service when patients start receiving these agents. Considerations for the transfusion service, both before and after initiation of anti-CD38 therapy, are detailed below.
The AABB Clinical Transfusion Medicine Committee has developed this bulletin to provide background information and guidance to members regarding anti-CD38 interference with serologic testing. The bulletin includes recommendations for its prevention and treatment.
Association Bulletins, which are approved for distribution by the AABB Board of Directors, may include announcements of standards or requirements for accreditation, recommendations on emerging trends or best practices, and/or pertinent information. This bulletin contains information and recommendations. No new standards are proposed.
Background
CD38 monoclonal antibodies are a new treatment for multiple myeloma
CD38, an integral membrane protein that is highly expressed on myeloma cells, has been identified as an effective target antigen for monoclonal antibody therapies. In November 2015, the first therapeutic CD38 monoclonal antibody [daratumumab (Darzalex, Janssen Biotech, Horsham, PA)] was approved by the Food and Drug Administration.1 Other CD38 monoclonal antibodies are under development.
CD38 monoclonal antibodies interfere with blood bank serologic tests
CD38 is weakly expressed on red cells. Anti-CD38 binds to CD38 on reagent RBCs, causing panreactivity in vitro.2,3 Plasma samples from anti-CD38-treated patients consistently cause positive reactions in indirect antiglobulin tests (IATs), antibody detection (screening) tests, antibody identification panels, and antihuman globulin (AHG) crossmatches. Agglutination due to anti-CD38 may occur in all media (eg, saline, low ionic strength saline, polyethylene glycol),
1
and with all IAT methods (eg, gel, tube, solid phase). Agglutination reactions caused by anti-CD38 are usually weak (1+), but stronger reactions (up to 4+) may be seen in solid-phase testing. However, anti-CD38 does NOT interfere with ABO/RhD typing or with immediate-spin crossmatches.
Other notes on anti-CD38 serologic interference:
 Adsorptions using either untreated or ZZAP-treated cells fail to eliminate the interference.
 Anti-CD38 variably interferes with direct antiglobulin tests (DATs) and antibody identification panel autocontrols.
 Some rare Lu(a–b–) cells are not reactive in the presence of anti-CD38, potentially giving the false impression that the patient has a Lutheran-related antibody.4,5
 Positive IATs can be observed for up to six months after anti-CD38 is discontinued.1,3
 Anti-CD38 may cause a small decrease in hemoglobin in vivo (~1 g/dL), but severe hemolysis has not been observed among treated patients.3,6
Anti-CD38 interference can cause delays in issuing RBCs
If the transfusion service is unaware that a patient has received anti-CD38, the following scenario may occur when the patient’s sample is tested:
1. ABO/RhD typing: no issues.
2. Antibody detection (screening) test: all cells positive.
3. Antibody identification panel: all cells positive (autocontrol may be negative).
4. DAT: positive or negative.
5. AHG crossmatches: positive with all RBC units tested.
6. Adsorptions: panreactivity cannot be eliminated.
This leads to delays in issuing RBCs to the patient. In some cases, the anti-CD38 interference could mask the presence of a clinically significant alloantibody.
Recommendations
To avoid problems with transfusion, hospitals should set up procedures to inform the transfusion service whenever any patient is scheduled to begin taking anti-CD38.
BEFORE a patient begins taking anti-CD38:
 A baseline type and screen should be performed.
 In addition, a baseline phenotype or genotype is recommended.
AFTER a patient begins taking anti-CD38:
 ABO/RhD typing can be performed normally.
 For antibody detection (screening) and identification, dithiothreitol (DTT)-treated cells can be used to eliminate the interference.2,7
o Because DTT treatment destroys Kell antigens, K-negative units should be provided unless the patient is known to be K-positive.
o Antibodies against other DTT-sensitive blood group antigens (anti-k, anti-Yta, anti-Doa/Dob, etc) will not be detectable when the antibody screen with DTT-
2
treated cells is performed; such antibodies are encountered infrequently, however.
Crossmatch
 For patients with a negative antibody screen using DTT-treated cells, an electronic or immediate-spin crossmatch with ABO/RhD-compatible, K-matched units may be performed.
 For patients with known alloantibodies, phenotypically or genotypically matched RBC units may be provided.6,8
o As some typing antisera require the use of AHG, phenotyping should be performed before the patient receives anti-CD38.
o Genotyping can be performed either before or after the patient receives anti-CD38.
o AHG crossmatches with phenotypically or genotypically matched units will still be incompatible.
o Some clinically significant antibodies may be missed with the use of uncrossmatched phenotypically or genotypically matched units, although this will occur infrequently.
 Alternatively, an AHG crossmatch may be performed using DTT-treated donor cells.
 If an emergency transfusion is required, uncrossmatched ABO/RhD-compatible RBCs may be given per local blood bank practices.
Future/alternative approaches to mitigating the anti-CD38 interference
It is possible to neutralize anti-CD38 in plasma and eliminate the interference using either recombinant soluble human CD38 or daratumumab idiotype antibody.2,3 Neither reagent is widely available at this time, and additional validation would be needed. In principle, soluble CD38 could be used to neutralize any anti-CD38, while different idiotype antibodies would be needed to neutralize different CD38 therapeutic antibodies. Finally, antigen-typed cord cells have been used for the antibody screen as an alternative to DTT-treated cells.9
3
References
1. Darzalex package insert. Horsham, PA: Janssen Biotech, 2015. [Available at: http://www.darzalex.com/shared/product/darzalex/darzalex-prescribing-information.pdf (accessed January 7, 2016).]
2. Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015;55(6pt2):1545-54.
3. Oostendorp M, Lammerts van Bueren JJ, Doshi P, et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion 2015;55(6pt2):1555-62.
4. Velliquette RW, Shakarian G, Jhang J, et al. Daratumumab-derived anti-CD38 can be easily Mistaken for clinically significant antibodies to Lutheran antigens or to Knops antigens (abstract). Transfusion 2015;55(3S):26A.
5. Aye T, Arndt PA, Leger RM, et al. Myeloma patients receiving daratumumab (anti-CD38) can appear to have an antibody with Lutheran-related specificity (abstract). Transfusion 2015;55(3S):28A.
6. Chari A, Satta T, Tayal A, et al. (2015, December) Outcomes and management of red blood cell transfusions in multiple myeloma patients treated with daratumumab (oral and poster abstract presented Monday, December 7, 2015, 6:00 PM-8:00 PM at 57th Annual American Society of Hematology meeting). Blood 2015;26(Suppl):Abstract 3571.
7. Chapuy CI, Aguad MD, Nicholson RT, et al. International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing (oral and poster abstract presented Monday, December 7, 2015, 6:00 PM-8:00 PM at 57th Annual American Society of Hematology meeting). Blood 2015;126(Suppl):Abstract 3567.
8. Hannon JL, Caruk B, Clarke G. Serological findings related to treatment with a human monoclonal antibody (daratumumab) in patients with advanced plasma cell myeloma (abstract). Transfusion 2014;54(2S):162A.
9. Schmidt AE, Kirkley S, Patel N, et al. An alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab (abstract). Transfusion 2015;55(3S):2292-3.
4

Interesting patient #2 this month.  A multiple myeloma patient who had no history had all testing positive in Gel, including the  Auto control.  Expecting a Warm auto we sent the specimen to the reference lab.  Again, they sent it further to the American red Cross.  They discovered a new medication on the med list was a medication that pretty much interfered with all blood bank testing except Immediate spin crossmatches.    Darzalex is the name of the drug.  The bulletin is below from the AABB.   So, while the patients are on this drug, our reference lab will have to perform the antibody screens for us. 
 
 
 
Association Bulletin #16-02
Date: January 15, 2016
To: AABB Members
From: Donna M. Regan, MT(ASCP)SBB—President
Miriam A. Markowitz—Chief Executive Officer
Re: Mitigating the Anti-CD38 Interference with Serologic Testing
Summary
A new class of therapeutic agents for multiple myeloma, CD38 monoclonal antibodies, can result in interference with blood bank serologic tests and thereby cause delays in issuing Red Blood Cell (RBC) units to patients receiving these agents. To minimize these delays, hospitals should set up procedures to inform the transfusion service when patients start receiving these agents. Considerations for the transfusion service, both before and after initiation of anti-CD38 therapy, are detailed below.
The AABB Clinical Transfusion Medicine Committee has developed this bulletin to provide background information and guidance to members regarding anti-CD38 interference with serologic testing. The bulletin includes recommendations for its prevention and treatment.
Association Bulletins, which are approved for distribution by the AABB Board of Directors, may include announcements of standards or requirements for accreditation, recommendations on emerging trends or best practices, and/or pertinent information. This bulletin contains information and recommendations. No new standards are proposed.
Background
CD38 monoclonal antibodies are a new treatment for multiple myeloma
CD38, an integral membrane protein that is highly expressed on myeloma cells, has been identified as an effective target antigen for monoclonal antibody therapies. In November 2015, the first therapeutic CD38 monoclonal antibody [daratumumab (Darzalex, Janssen Biotech, Horsham, PA)] was approved by the Food and Drug Administration.1 Other CD38 monoclonal antibodies are under development.
CD38 monoclonal antibodies interfere with blood bank serologic tests
CD38 is weakly expressed on red cells. Anti-CD38 binds to CD38 on reagent RBCs, causing panreactivity in vitro.2,3 Plasma samples from anti-CD38-treated patients consistently cause positive reactions in indirect antiglobulin tests (IATs), antibody detection (screening) tests, antibody identification panels, and antihuman globulin (AHG) crossmatches. Agglutination due to anti-CD38 may occur in all media (eg, saline, low ionic strength saline, polyethylene glycol),
1
and with all IAT methods (eg, gel, tube, solid phase). Agglutination reactions caused by anti-CD38 are usually weak (1+), but stronger reactions (up to 4+) may be seen in solid-phase testing. However, anti-CD38 does NOT interfere with ABO/RhD typing or with immediate-spin crossmatches.
Other notes on anti-CD38 serologic interference:
 Adsorptions using either untreated or ZZAP-treated cells fail to eliminate the interference.
 Anti-CD38 variably interferes with direct antiglobulin tests (DATs) and antibody identification panel autocontrols.
 Some rare Lu(a–b–) cells are not reactive in the presence of anti-CD38, potentially giving the false impression that the patient has a Lutheran-related antibody.4,5
 Positive IATs can be observed for up to six months after anti-CD38 is discontinued.1,3
 Anti-CD38 may cause a small decrease in hemoglobin in vivo (~1 g/dL), but severe hemolysis has not been observed among treated patients.3,6
Anti-CD38 interference can cause delays in issuing RBCs
If the transfusion service is unaware that a patient has received anti-CD38, the following scenario may occur when the patient’s sample is tested:
1. ABO/RhD typing: no issues.
2. Antibody detection (screening) test: all cells positive.
3. Antibody identification panel: all cells positive (autocontrol may be negative).
4. DAT: positive or negative.
5. AHG crossmatches: positive with all RBC units tested.
6. Adsorptions: panreactivity cannot be eliminated.
This leads to delays in issuing RBCs to the patient. In some cases, the anti-CD38 interference could mask the presence of a clinically significant alloantibody.
Recommendations
To avoid problems with transfusion, hospitals should set up procedures to inform the transfusion service whenever any patient is scheduled to begin taking anti-CD38.
BEFORE a patient begins taking anti-CD38:
 A baseline type and screen should be performed.
 In addition, a baseline phenotype or genotype is recommended.
AFTER a patient begins taking anti-CD38:
 ABO/RhD typing can be performed normally.
 For antibody detection (screening) and identification, dithiothreitol (DTT)-treated cells can be used to eliminate the interference.2,7
o Because DTT treatment destroys Kell antigens, K-negative units should be provided unless the patient is known to be K-positive.
o Antibodies against other DTT-sensitive blood group antigens (anti-k, anti-Yta, anti-Doa/Dob, etc) will not be detectable when the antibody screen with DTT-
2
treated cells is performed; such antibodies are encountered infrequently, however.
Crossmatch
 For patients with a negative antibody screen using DTT-treated cells, an electronic or immediate-spin crossmatch with ABO/RhD-compatible, K-matched units may be performed.
 For patients with known alloantibodies, phenotypically or genotypically matched RBC units may be provided.6,8
o As some typing antisera require the use of AHG, phenotyping should be performed before the patient receives anti-CD38.
o Genotyping can be performed either before or after the patient receives anti-CD38.
o AHG crossmatches with phenotypically or genotypically matched units will still be incompatible.
o Some clinically significant antibodies may be missed with the use of uncrossmatched phenotypically or genotypically matched units, although this will occur infrequently.
 Alternatively, an AHG crossmatch may be performed using DTT-treated donor cells.
 If an emergency transfusion is required, uncrossmatched ABO/RhD-compatible RBCs may be given per local blood bank practices.
Future/alternative approaches to mitigating the anti-CD38 interference
It is possible to neutralize anti-CD38 in plasma and eliminate the interference using either recombinant soluble human CD38 or daratumumab idiotype antibody.2,3 Neither reagent is widely available at this time, and additional validation would be needed. In principle, soluble CD38 could be used to neutralize any anti-CD38, while different idiotype antibodies would be needed to neutralize different CD38 therapeutic antibodies. Finally, antigen-typed cord cells have been used for the antibody screen as an alternative to DTT-treated cells.9
3
References
1. Darzalex package insert. Horsham, PA: Janssen Biotech, 2015. [Available at: http://www.darzalex.com/shared/product/darzalex/darzalex-prescribing-information.pdf (accessed January 7, 2016).]
2. Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015;55(6pt2):1545-54.
3. Oostendorp M, Lammerts van Bueren JJ, Doshi P, et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion 2015;55(6pt2):1555-62.
4. Velliquette RW, Shakarian G, Jhang J, et al. Daratumumab-derived anti-CD38 can be easily Mistaken for clinically significant antibodies to Lutheran antigens or to Knops antigens (abstract). Transfusion 2015;55(3S):26A.
5. Aye T, Arndt PA, Leger RM, et al. Myeloma patients receiving daratumumab (anti-CD38) can appear to have an antibody with Lutheran-related specificity (abstract). Transfusion 2015;55(3S):28A.
6. Chari A, Satta T, Tayal A, et al. (2015, December) Outcomes and management of red blood cell transfusions in multiple myeloma patients treated with daratumumab (oral and poster abstract presented Monday, December 7, 2015, 6:00 PM-8:00 PM at 57th Annual American Society of Hematology meeting). Blood 2015;26(Suppl):Abstract 3571.
7. Chapuy CI, Aguad MD, Nicholson RT, et al. International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing (oral and poster abstract presented Monday, December 7, 2015, 6:00 PM-8:00 PM at 57th Annual American Society of Hematology meeting). Blood 2015;126(Suppl):Abstract 3567.
8. Hannon JL, Caruk B, Clarke G. Serological findings related to treatment with a human monoclonal antibody (daratumumab) in patients with advanced plasma cell myeloma (abstract). Transfusion 2014;54(2S):162A.
9. Schmidt AE, Kirkley S, Patel N, et al. An alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab (abstract). Transfusion 2015;55(3S):2292-3.
4

Thank you for your reply.  This makes sense to me.  Better to be safe since he has had prior transfusions even if it was 3 years ago.  When he comes back in we will re-screen him and then once he is transfused he will be treated normally, we will just have to send his sample to the ARC for the special tesing.  

So, interesting patient last month.  We had a patient with a history of anti-e. (not good)  Worked her up and every cell on the panel was positive (even the e neg antigen cell).  Her auto control  and DAT were negative.  Come to find out after sending her to our reference lab for a full work up, which then sent her to the American Red cross that she has developed anti-Kpb.  She was Kpb antigen negative.  She would need blood negative for K, Kpb, e and C (could not rule out big C).   After a long search she is not compatible with any of the blood (rare donor databases I am assuming) in the US.   If we wanted to start a global search the physician would have to get in contact with the director the ARC directly.  It was crazy!  We are a small hospital who never sees this kind of crazy stuff, but I guess it was our turn.  (The patient is responding to iron treatments and has been doing ok with out blood transfusions thus far.) 
 
 

Yes, that is what I tell them. 

Thank you everyone for your feedback! 
 

In the USA, all AABB accredited IRLs (Immunohematology Reference Laboraotories) and American Red Cross IRLs are members of the American Rare Donor Program (ARDP). This program has over 45,000 Rare Donors registered from over 88 member centers. If your blood supplier is not a member of the ARDP,  your facility can access the program by sending a sample for evaluation to a member. If there are no member centers in your area, the Penn-Jersey American Red Cross can be a "portal" to the ARDP. After a sample is submitted and tested, Penn-Jersey will access the ARDP for the non-member hospital or blood center. Ninety four percent of the time, units are found.  In very complex cases, there may be no blood available. If the blood is not avaiable in the USA, then the ARDP, as a member of the World Health Organization (WHO) International Rare Donor Panel(IRDP), can request blood internationally after several qualifying steps are taken (prove no blood in USA, eligible sibling donors have been tested, MMA performed, patient and physician give permission). The WHO IRDP is managed by the International Blood Group Reference Laboratory headquartered in Bristol, UK under the direction of Nicole Thornton. No patient should be without the blood they need to survive, although some are very very rare with very few identified donors in the world [e.g. Rhnull, En(a-), Ko, Co(a-b-)] and that makes it difficult to supply lifesaving blood.
Sandra Nance, Senior Director, American Rare Donor Program, 1- 215 451 4362

Thanks for that.  Anti-U is a bit of an enigma.  The first two described were responsible for a fatal HTR and an IUD, but the vast majority, at least as far as HDFN are concerned, But also many as far as HTR are concerned, appear to be clinically benign - and nobody seems to know why (with any certainty).  My pathologist and I thought that it might be that they are of the "wrong" IgG sub-class, but we haven't been able to prove this yet!  Both true U Negative individuals, and U variant individuals can produce an anti-U, but the latter tend to produce an anti-U that is low titre; I just wonder if your lady is a U variant, rather than a true U Negative (all individuals of both types are S-s-, but many examples of anti-U do not react with U variant red cells).  The U antigen and anti-U can be a right pain!!!!!!!!!!!
I think your idea of autologous donation is extremely sound!

They're not going to die from that though - a DHTR may occur, but there have been cases where Kpb+ units have been transfused without any shortening of the red cell lifespan. They may have unpleasant clinical manifistations that the clinicians can deal with at some point but this is a better option than exanguination.
Stick them on iron, B12, folate and erythropoetin and they will produce their own red cells pretty sharpish - hopefully quicker than the transfused cells are destroyed with a DHTR.
As long as the clinicians are aware that it is going to happen, they can deal with it.

I have started dating stuff in my fridge at home.  I hate not knowing when it was opened!  haha

A small facility doing a lot of blood banking by generalists should seriously consider an automated testing platform.  Automated testing eliminates a wide range of errors associated with specimen identification, test tube labeling/handling, results entry, results interpretation and transcription. 
 
Our platform prints a report with results and results interpretation.  We affix a barcoded sample label to the report (one patient per sheet of paper).  The barcode on the report is scanned into the LIS result entry routine and results are transcribed.  This system works 24/7/365 with a single individual wholly responsible for results entry.  I have used this system successfully over the past 10 years, both in a 525 bed Level II trauma center (>10000 rbcs transfused annually) and a 100 bed (<50% occupancy) community hospital(<1100 rbcs transfused annually).
 
I believe that any strategy that relies on double-checking a process by multiple individuals will fail.  If an individual cannot accurately transcribe results in the system described above, they should not be working in a transfusion service.
 
Blood bankers need to embrace automation in the 21st century and discard 20th century manual processes.
 
Whew!!,  I feel so much better now.  Thanks.

We have the same - manual gel and tube ABO. 
What we do here is have a second field in the LIS for an ABO check and Screen check.  The first tech performs the test and enters their results in the LIS.  The first tech then leaves all the tubes and card in the rack. The second tech checks re-reads the tubes and card and verifies the results are correct in the LIS.  The second tech must fill in the "check" field with their initials.  They don't retest - they just check.
I should note, we don't hold back any blood products until the second check has been completed.
Hope that helps! 
I'm going to follow this to see if there are any great ideas for us as well