ElinF

If we find we don't have history on any crossmatch patient (or type and screen that could turn into a crossmatch) we search for another tube we may have the lab (samples from the past week). Other than that we had to start accepting draws from all over the hospital with the nurse's identification (which was hard for us small lab blood bankers to do...we want to control it all!) If needed we then send the phlebotomist out and get a 2nd tube (which we usually use as the crossmatch tube and the nurse draw as the confirmation tube.) If we cannot get a confirming 2nd tube we give universal products until we can get a confirm tube. If the patient is originally O positive or negative, we don't confirm them with a 2nd type because they will get O anyways. (unless they are getting FFP). I feel so much more comfortable doing this. I hated giving blood on just 1 draw ABO results! Hope this helps.

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.

I am wondering what the timeframe is at other facilities We have never had to extend anything longer than a week. We are a smaller hospital and we don't do many surgeries requiring blood. Other places on this website say 30 days. We are getting to the 30 day mark, so I am sure he will be rescreened, but having had no transfusions, I was wondering how long we could extend.

So question then...We have our patient typed and screened. He has not received blood in 3 months or has been pregnant (obviously). How long can we extend his original crossmatch/antibody ID specimen that we had send to the Red Cross and was found negative. How long can we honor that antibody screen. Can we redraw just for the Immediate spin crossmatch if he were need to be transfused in the upcoming weeks? It has already been probably a month, and he is holding strong. but I was just curious what everyone's policies were. Ours really doesn't give a long date. We have never had this come up.

Thank you everyone for your feedback!

Yes, that is what I tell them.

So, what would happen if she were to get into a trauma situation. what are the chances giving her blood would actually hurt her in an acute situation? That is what everyone is asking me...

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

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.)

We just have an emergency release form too. Ours states "Because the delay in transfusion will jeopardize the patient's life, I accept the responsibility for any adverse recipient reaction resulting from this transfusion. I understand laboratory personell will compete the required testing and report immediately any unacceptable results." Doc signs. Kind of a catch all. The blood bank tech would be talking to the physician. Usually when we say things like antibody or incompatible it scares them off enough to wait (if it is a chronic issue, slow GI bleed etc) until we are done. If the patient is bleeding out they just get the O neg blood, but we do tell them of the situaion. If there was an antibody situation the pathologist would be notified along with our lab manager and Nursing/Hospital supervisor. However, I like the forms stated above that make the doctor check which one so they know what they are getting and if it is compatible or not.

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

Hi all, Sorry I am just getting back to this. Thanks for your responses. As far as more info for our situation...We perform manual gel on all antibody screens and prenatal type and HDN ab screen. We do tube ABORH on crossmatches because it is quicker. We currently have 1 tech by herself after 10 pm. We are in the works for getting automation- waiting for the Ortho Vision to come out this spring, but you know how that goes... We are building our case and have looked at other facilities and their automation. Our clerical errors occurred on patients that did not have any current history in our system. We have an LIS that will catch errors. We are also reading right from the medium. Our crossmatch/transfusion policy is to have 2 types performed on the patient from 2 separate draws (unless they are type O and yes we would give women of child bearing age O neg blood if we only had 1 chance at an ABO before transfusion) so we are doing good there. Many discussions in OB with that one! The problem with the 2 errors was #1 it was lone midnight shift tech working up a emergency release and she must have had O neg on the brain. She reported O neg instead of O pos on the patient type. A second look may have found this error. (the bad/good thing is was this patient was transferred out to a sister facility and they caught our error. No harm to the patient obviously, but it is still an embarrassing error in which she felt horrible for). #2 was I believe a misread- mixing up 2 patients. She reported out A pos for both patients instead of AB Pos for 1. Again, clerical. We do have a 1 rack per patient policy, but she must not have followed it... We currently review any result that gets manually entered for other departments (when we have to report them off printer tapes and such) so I think implementing this for blood bank is way overdue. Let’s see, I think I addressed most questions?? Thanks again for your comments and discussion! Always so interesting to see what everyone else does! Elin

We perform QC with our Positive QC reagent (ortho confidence) on receipt of the new gel panel. We only perform QC on the tube panels if we need to use a cell for rule out.

We are a smaller hospital lab but we do a lot of blood banking. We currently perform manual gel with Tube ABOs for our crossmatch patients. We have had 2 recent errors in ABO reporting that were clerical errors so something has to be improved. We currently do not do a 2nd tech review of our manual entry results. Does anyone have a good process flow for this? What do you do for techs that work by themselves on 2nd/3rd shift? Elin

Quick question... What is everyone's policy on ABORH testing for outpatients receiving platelets? Right now we do an ABORH on patients for every out patient encounter. Sometimes that gets very redundant if they come in say every day for 4 days. I haven't really found in the standards what is optimal for this situation. We have since changed it to every 3 days, but I think our pathologist was confusing the whole antibody formation time frame. Thoughts?

Thank you to everyone who had to work Christmas Day. I will probably next year. Anyone with kids, how do you work out christmas day? Do you open presents from santa Christmas Eve? Have them get up real early and open before work? Just curious!

We actually had a patient like this and we have had her though 2 pregnancies. The first time around we were all nervous because the anti-E was 4+. Very strong. We monitered her every month (the titers never increased), had the dad tested (which he was Big E negative). Baby was born and baby was big E negative as well. Of course we maybe thought a little funny business was going on, but we had to trust the mother that everything was as it should be. I was in a conference once where they stated that this can occur during pregnancy? Naturally occuring anti-E during pregnancy. I was like hey we had one of those! We never have blood from her when she is not pregnant, so I haven't been able to test it to see if it goes away. It was interesting. Scary at first, then interesting. (I actually had a nephew who had hemolytic disease of the newborn with kernicterus-which later we learned was more due to a brain bleed then antibodies, but none the less I am a little sensitive to HDN as I am sure we all are)

This is what I was thinking. I would have long since killed them with my emergency release O neg units. Not a good outcome, but that is probably what would happen.

I am currently working on a cold procedure because EVERYTIME we get one (which is pretty frequently in gel) it is this huge ordeal that ends up being nothing. We have just purchased PEG and will be using that in a tube screen. We usually see these in the gel screen, all 3-4+. We then do a tube screen in 4c. If positive, it is a cold. Run screen with PEG and the colds shouldn't interfere. (at least that is what I am hoping because that is what I have been told.) If the tube screen is negative we would go ahead and do the AGH crossmatch since the IS will probably be positive. I am still a little iffy on what do to as far as the crossmatch though. Our reference lab says no AHG crossmatch in this situation, but I think I would want to since there were issues.

So, is it ok to rule out C and E on heterozygous cells when anti-D is present ? I always thought it was, then read somewhere that it wasn't, so we started giving E negative blood since it is alomst impossitble to rule out with homozygous. Are we doing too much work?

I agree that in this instance i would worry more about the ABO discrepency and do regular crossmatches if it negative, but if you are looking at a cold ab, could you just do your 4C incubation, determine it is a cold, and then do a tube screen with PEG to rule out clinically significants?

I am totally printing out her response and letting students read it. Very well written.

Usually we just do 20 day testing of our QC and 10 positive antibody samples and 10 negative samples. But you are right, as long as QC works, we should be good to go. Our major concern too was not having that 3rd cell to narrow it down...

We do and I love it. I feel so much more confident in issuing A, B, or AB blood. I always hated giving a "new" patient say A+ blood just off that one draw. We now have a policy for ABO repeats. Patient's without any sort of historical blood type get redrawn. An exception is if you are type O. We just go with it if you are type O. We are just looking for ABO disrepencies. If it is an emergency, say surgery or ER, we just give O blood until we can confirm type.