Rapid onset of pos DAT

[Mabel Adams]

We had a pregnant patient that had a type and screen for a c-section. The screen was positive due to antenatal RhIG. She had the misfortune to have breast cancer also so had a mastectomy about 3 days after delivery. They ordered a repeat Type and Screen for this also and of course, she still had a positive screen--just the anti-D. However, her DAT had been negative with the first Ab ID but was 3+ with IgG on the 2nd specimen (neg with anti-c3). She was on cephalosporins for her surgeries.

Any explanations you would like to put forth?

[Malcolm Needs ☆]

????????????drug-induced AIHA??????????????????

[John Eggington]

Also, did they start giving her any other drugs/treatment, after delivery, that had been held back because the pregnancy? A big dose of 'something new' (or a switch from oral to IV cephalosporins) might cause a positive DAT.

[David Saikin]

cephalosporins are notorious for drug-induced AIHA when used prophylactially

[Mabel Adams]

No signs of any chemo yet or any other drug that I would suspect as a cause. If it is drug-induced pos DAT (no evidence of hemolysis but they did not do any blood work after the day the DAT was detected--but no mention of juandice etc.) what would you do? Should I call her MD and make them aware to watch for future problems if they use cephalosporins? Try to get them to send out a sample for testing for the antibody? Is there evidence of people making the antibody but never progressing to Hem anemia even if re-exposed to the drug? Leave it be until something definitive happens? This patient lives several hours from here and an hour plus from the nearest tiny hospital. She was discharged about a week ago, so if anything was going to happen this time, it probably already would have.

[Malcolm Needs ☆]

At the very least, I would inform your Pathologist - just to be on the safe side.

[Liz]

I agree that Cephalosporins can cause drug-induced AIHA.

[galvania]

And advise them to stop the cephalosporin just in case. Drug induced AIHA should not be taken lightly. It can be fatal

[Mabel Adams]

Update: I finally got around to asking my blood supplier's medical director and she thought we should get the patient tested for antibody to cephalosporins. In the process of finding out what specimens they wanted, my reference lab referred me to Dr. Garratty's research lab in Calif. They pointed out that most people that develop cephalosporin DIAHA actually start hemolyzing about 1-2 weeks post drug. Cefotetan is the most common of these drugs implicated although ceftriaxone seems to be more deadly. A reference book says that people can make the drug antibody and have a pos DAT without hemolyzing. By this time our patient was right in the hemolysis window. My pathologist called the oncologist who said she would have the patient tested for hemolysis nearer her home. A couple of days later we got an antibody ID on her from the tiny hospital nearer her home. Just the anti-D was found and they neglected to send cells so a DAT/Auto control wasn't done. Then about 3 days after that she was back in our facility to have a port placed for chemo. Her Hct was ok. About then another oncologist from that practice called to find out what we had done on her previously and mentioned that he thought she had shown signs of hemolyzing. So I called the small hospital and found out she came in with a 6 g Hgb and they gave her 4 units! They finally sent us her cells and we found the DAT was still 1+ with anti-IgG and now a weak pos with anti-C3b,C3d. They ran a bili on that now 4 day old sample and found it only minimally elevated. Before the transfusion she had an MCV of 115 and RDW of 20 with a normal MCHC so she was probably making massive amounts of retics. My gut says that's more consistent with hemolysis than post-c-section blood loss. As far as I know no other tests for hemolysis were done and I have no report of the patient's signs and symptoms during that week at home. We finally gathered up everything and sent it to California for a test for antibody to cefotetan which she got with the c-section. I suspect that she did most of her hemolyzing before she came in for the transfusion and her bili was actually coming back down to normal. We will see what the antibody workup says. I have seen one other case of this and it was bad so it is worth all BBers being aware of it.

[profbaud]

Cephlasporins do cause a strong positive DAT with IgG. The mechanism is like penecillin where the person makes an antibody to the drug and attaches to red cells. If you perform an eluate and run it against a regular panel, it will be negative.

[Mabel Adams]

The report came back positive for antibody to cefotetan in both serum and eluate. We sent out a letter saying to avoid cefotetan forevermore to every doctor that we knew had seen he and the other hospital and called our pharmacy to have it added as a drug allergy to her EMR. She is actually lucky that she is Rh neg or we would never have done a DAT (we do them only with IDs) and she might have got the same drug in future with even worse hemolysis.

[emadlabs]

hi can you tell me what is the source or reference for this information with my thanks

cephalosporins are notorious for drug-induced AIHA when used prophylactially

[Liz]

"Cephalosporins (primarily cephalothin) are the drugs with which positive DATs and nonimmunologic protein adsorption were originally associated"

AABB Technical manual and Garratty G, Arndt PA. Positive direct antiglobu- lin tests and haemolytic anaemia following ther- apy with beta-lactamase inhibitor containing drugs may be associated with nonimmunologic adsorption of protein onto red blood cells. Br J Haematol 1998;100:777-83.

[DMR]

Along with cephalosporins, for AHIA, watch for cefotetan administration pre-c-section. We had a situation where post c-section delivery the patient developed severe anemia Hgb <5.0 gm/dl. She had been given penicilin G post delivery, Cephalosporin, Aldomet (both given during the pregnancy) and Cefotetan. We sent her specimen out for testing and they found antibodies to penicillin and Cephalosporin that were weak. The also found that she had a strong reacting antibody to cefotetan. After searching her chart, we found one notation that cefateton in the anesthesia notes being given pre-c-section. Our Anesthesiologist indicated that cefatetan pre-c-section is quite common. The reference lab BB Specialist, says that when they see severe hemolysis post c-section, they often find antibodies to Cefatetan. I believe there are articles on this written by Garatty that explain the mechanism.

[Liz]

Malcolm, Cliff did you know that one can thank oneself?? I was thanking myself for my references and it worked. How embarassing.. I removed it of course. I believe that no one would do it because it shows. ) Please Cliff leave it as is lest the thank you button gets spoilt. Thank you.

[Malcolm Needs ☆]

Yes, leave it there Cliff. I shall be thanking myself for all of my posts from now onwards!!!!!!!!!

:judge::judge::judge::judge::judge:

[L106]

Way to go, Malcolm!!

Donna

[AMcCord]

My first patient with a cefotetan induced hemolytic anemia was ...... a C-Section! She had premature rupture of membranes and they treated her with cefotetan prior to the C-section. After delivery she spiked temps (the hemolytic episodes) and so they decided to have her come in to get further IV cefotetan every 12 hrs, thinking that her fever was a sign of postpartum infection. She started feeling really lousy over the weekend (hemolytic episodes and increasing anemia) and saw her doctor first thing Monday morning. He was alarmed by her 4.0 Hbg, enlarged spleen and yellow eyes, so sent her over to the hospital for a CT and labs to work her up for anemia. He did order the right labs for possible hemolytic anemia (pretty good for a family practice doc), but he wasn't thinking about the cefotetan at that point. Her plasma was a very dark olive green with all the results you'd expect - high retic, high bili, high LDH, high plasma Hgb, pos DAT (clumped 4+ without centrifugation) and negative antibody screen. When our pathologist called him and asked about antibiotic therapy, the doc immediately grasped the problem...the cefotetan. This case was right about the time that the word was getting out about problems with hemolytic anemia with 2nd and 3rd generation cephalosporins, so he'd been doing his homework. The patient was treated aggressively with solumedrol and we transfused her over 3 days. She went home feeling much better. She was advised to avoid cephalosporins, especially cefotetan.

I'd gone to a workshop about a year before where this was one of the topics presented. I figured it was only a matter of time before we saw a good case, so I was watching for the problem. As soon as I heard she had been getting cefotetin, I knew that's what we were dealing with. I played with a sample of the batch of cefotetin she got and coated some red cells with it to prove the theory of a cephalsporin antibody - not normally something I do here. It worked great. Her antibody reacted 4+ with the treated cells. What fun! (Blood Bankers are a little weird, aren't we, considering what we think is fun?) The ARC reference lab titered her antibody out to something in the 14,000 range, which is actually not that high for this type of antibody. Interesting case. It also served to educate the physicians at our facility about the possibilities of antibiotic induced hemolytic anemia. There was a great deal of discussion in the physician lounges.

Edited June 7, 2011 by AMcCord

[Mabel Adams]

Education of physicians is part of the reason I blitzed all her providers with her results and an article the reference lab sent on cefotetan induced hemolytic anemia post C-section. Blood Bankers need an awareness too because the fever makes the docs think infection and give more of the drug unless someone suggests this cause.

[Liz]

You are absolutely right, Mabel. We think that what we know is common knowledge and the physicians know it.... they don't.

[AMcCord]

Thumbs up Mabel! I agree with you 100%.

[ballp]

Several years ago we had a patient's sample referred to us. The patient had died after a C-Section. The reason for the death turned out to be Cefotetan. Just the mention of that drug strikes fear in all the technologists in my IRL. Appears this patient was lucky.

[LaraT23]

I had this happen here last year. This time it was an older male being treated for myelodysplastic syndrome secondary to an unknown. His bone marrow was really suppressed and he got a lot of upper resp. infections. He came in about a week post outpatient transfusion, with olive green to black serum, horrible jaundice and a hgb of 5.5. Of course the blood banker on duty thinks, delayed HTR. But found nothing in the panel. He reacted but very nonspecfic and had strong DAT. So, we did a little digging and found that he reacted much more strongly in the gel than in the tube. Come to find out that there is antibiotic included in the gel as a preservative. I called the doc and talked with her about all of our findings and she took him off his current course of antibiotics and switched him to non cephalosporins. Low and behold he perked up, stopped hemolyzing and had normal colored serum about a week later. Very important to keep the role of antibiotics and other meds in mind when investigating these cases.

[Mabel Adams]

Well, we just had another case that looks like cefotetan antibody.  Should get the test results in the next day or so.  This one was a woman in a couple of weeks ago for bowel surgery.  When she came back in this week with nausea and vomiting she had a bili of 7 so they did a DAT, LDH etc. Her Hgb was about 10.  The next morning it was 5.6!  When they ordered blood and the tech got a negative Ab screen, she put together the clues that the patient had a positive DAT the day before and a recent inpatient visit with this crashing hemolysis so checked drug history and found cefotetan given at the time of the surgery.  She notified the hospitalist and they put her on steroids promptly so her hgb is stabilizing but her bili was up to 11 today.

 

Does anyone have a good case study or bullet point list that is more from the clinical presentation side rather than the labwork side?  I would like to try to help ED doctors know to think of this but it seems like the patients present in a lot of different ways.  This is our 3rd case in 5 years and the Blood Bankers have caught them all.  BTW, these 3 patients are all A neg (2) or A pos (1).  Is this just coincidence or are group A people more at risk of this hemolytic anemia?

[mollyredone]

Mabel,

I'm so glad you posted an update! We haven't had any situations like that here that I know of, but this reminder will help jog my memory...at least for a little while!