neonatal exchange transfusions

[BBK710]

Because it is necessary to register with the FDA to prepare recombined whole blood for exchange transfusion I know that many hospitals have stopped providing the service to their nicu. The babies are transferred to a facility that can provide the service.

I am interested in knowing what hospitals that are not FDA registered and only do the procedure once every few years have done or are planning to do about exchange transfusions.

I am more concerned about the competency of staff performing the preparation of the product and the procedure itself than the FDA registration (although I would like to avoid that if possible since we have only done 2 exchanges in the last 8 years.)

[BSIPHERD]

We worked with our blood supplier and prepare reconstituted whole blood for us for an exchange transfusion when needed. Thanks Nebraska Community Blood Bank!

[Antrita]

We are in the middle of adding a NICU to our hospital. I contacted the FDA and we had to register with them because our blood supplier does not reconstitute blood for us. The easy part is the registration. We had to do an exchange transfusion 2 weeks after we got our registration and before we even did a simple transfusion. We have only 1 CLS on nights and 2 on pm shift so we have decided when exchange transfusion is ordered on these shifts either myself or the lab manager will come in and help. Hopefully we will only have 2 in 8 years. It is very labor intensive to make up the reconstituted units.

[shelleyk482]

Our supplier will furnish reconstituted whole blood however we are more than 2 hours away from them (in a snow-prone area). Our procedure is written to state that the preferred product is purchased from our supplier but it goes on to define an in-house process of making the product. It is clearly stipulated that this is to be used only if the medical situation is so critical that the delay (which would be a total of 4 hours on a good day) in product availibililty would be life-threatening for the neonate. Our medical director must consult with the neonatologist prior to the product being made in-house and since the medical director is well aware of the implications of this being done in-house on a routine basis without FDA registration, it would take a lot for him to approve.

In the year since we made this new policy, we have not had an order for an exchange transfusion. Our feeling is that since this would be such a rare occurrence that when it does happen, it can be handled as a medically emergent procedure, and it would be thoroughly documented as such, that FDA registration would not be required. If we start producing the product on a fairly routine basis (probably more than 3/yr) then we would look at the necessity for FDA registration.

From my understanding, after speaking with FDA inspectors in the past, concerning "rare" events such as this, that it is an acceptable approach. You just need to continually review the number of occurrences and assure that it is truly a "rare" occurrence that is used in life-threatening situations where the are no viable alternatives. It has been quite some time since I have broached this general topic with an FDA inspector so I can't guarantee that this is still FDA stance, but to me this is an approach that makes sense and that I would feel fully comfortable in defending.

[bbbirder]

I found this comment on the CBBC web forum and added it to another thread here, but I haven't had any comments.

Any thoughts on the idea of using AS red cells just as they are?

"A colleague from Spain reports that in his opinion, he agrees that the best place to prepare the component is the blood bank laboratory, and that one should take into account the following (his opinion paraphrased is shown below):

• The desired hematocrit is a critical issue, since the neonate hematocrit is physiologically higher that the adult. If you use an adult hematocrit (about 35-40%) for a baby with 55%, you can cause hemodilution. In the actual clinical case, the neonate could have low or high hematocrits, and the reconstituted blood should help the baby reach a desired level.
  

If you want to minimize donor exposure, maybe it is not necessary to use whole blood. The hematocrit of red blood cells in additive solution (i.e. Adsol, SAG-mannitol) is usually within the clinically desired range. In this way, you should only use plasma if the baby shows additional coagulopathy (this is standard practice in the British Health Service). The case for washing red cells could arise from mannitol-containing solutions if the baby is not stable. Sometimes the pediatrician feels safer without manitol."

[Mabel Adams]

I wish someone could give us hard and fast answers regarding the use of additive units for exchanges (reservations mostly due to the mannitol question). I know they are fine for small transfusions but have not felt very comfortable with them for exchanges. I think I have heard of some places spinning down the unit, pulling off most of the additive and replacing with plasma. Then you are back to the FDA issue.

One thought on the emergency use---it usually takes at least a few hours, sometimes a day or two, until the baby's bili is high enough they know they need to exchange, thus it is often not a truly emergency situation, usually allowing time to ship in a product. The most severe HDFN babiies will be born with hydrops due to severe anemia so may have a need for an emergency transfusion, but this could possibly be met with a small volume transfusion. Then preparations can be made for the exchange when the bili starts to rise. This is more my experience from a hospital that did not deliver the worst such cases--those would probably deliver in a large city with a supplier across town--at least in Oregon. Of course, I don't think our ARC supplies reconstituted units so it would then be an emergency to produce one in-house, not because there is not time to get one, but because no such product is available by other means. They are usually not licensed products so the suppliers can't ship them across state lines and get paid for them. That precludes finding a distant supplier to ship you one unless they want to do it gratis.

[Malcolm Needs ☆]

I must admit that I was/am curious to know why, in these days of vastly improved antenatal care, with MCA Doppler/ultrasound commonly available and planned delivery, any lady with an at risk pregnancy is not sent to a Specialist Fetal medicine Unit for pre-natal care and, if necessary, delivery; certainly in the USA?

Except in cases of severe ABO HDN in the first pregnancy (very rare) or HDNF due to an antibody that was not detected during the pregnancy (either because it was directed against a low incidence antigen, or because the lady did not attend antenatal appointments), such emergencies in a "local" hospital (sorry for the derogatory term - I've been racking my brain for the correct term and have failed miserably) should be exceedingly rare, and it follows that the need for such emergency blood should be equally rare.

As I say, I'm more curious than anything else.

:confuse::confuse:

[bbbirder]

We have women show up 'on the doorstep' with no prenatal care.

We recently had one show up to deliver her 2nd child, no prenatal care. Her first baby had been born with a PLT count of 12,000 and was flown out. Diagnosis: Neonatal Alloimmune Thrombocytopenia.

You'd think she'd be a little worried about the next one, but I guess not!

Then there are snow and ice storms that ground helicopters and prohibit any ground transportation. (Like the woman visiting from out of town, sudden fetal demise, went into DIC. BIG ice storm, unable to transport... we used expired PLTs that night... with pathologist permission, of course.)

[Malcolm Needs ☆]

Oh yes. I am not saying that this kind of emergency cannot happen. All I'm saying is that, these days, they should be exceptionally rare.

[Antrita]

Our patient was on her 11th pregnancy with only 1 live birth (the first). She went to her OB at the beginning of her pregnancy and then nothing until 37 weeks. At this point they did a emergency c-section. The baby had a 5 hgb and a very high bilirubin.

We registered with the FDA because I have no idea how many exchange transfusions we will have as we are just started up our NICU. The fact that our first transfusion was an exchange transfusion may not be a good sign. I'm not sure why registering with them should be avoided at all costs as some have told me. Do they inspect every one that is registered?

[Malcolm Needs ☆]

Our patient was on her 11th pregnancy with only 1 live birth (the first). She went to her OB at the beginning of her pregnancy and then nothing until 37 weeks. At this point they did a emergency c-section. The baby had a 5 hgb and a very high bilirubin.

We registered with the FDA because I have no idea how many exchange transfusions we will have as we are just started up our NICU. The fact that our first transfusion was an exchange transfusion may not be a good sign. I'm not sure why registering with them should be avoided at all costs as some have told me. Do they inspect every one that is registered?

What was her antibody(ies)?

I know that we are not supposed to make moral judgments, but it seems to me that, if she had already lost 9 babies, anyet still had such disregard for the child she was carrying in her 11th pregnancy, the FDA should have looked at her and taken away her license!!!!!!!!!!!!

:eek::eek:

[RR1]

What was her antibody(ies)?

I know that we are not supposed to make moral judgments, but it seems to me that, if she had already lost 9 babies, anyet still had such disregard for the child she was carrying in her 11th pregnancy, the FDA should have looked at her and taken away her license!!!!!!!!!!!!

:eek::eek:

Many patients are scared of hospitals, these things happen. A lack of understanding and other social problems may also be a cause, but as you have said we aren't here to judge them.

A good concessionary testing and exceptional release policies should cover these rare events when we need to deviate from our normal procedures.

[Antrita]

Our patient population is such that is not unusual for us to get patient's with no prenatal care. I must say though that I've never seen a Rh baby like this. The neonatalogist said she was dating herself because as soon as she saw the baby she knew exactly what was going on and what we had to do. I'm glad we did one, it makes a straight NICU transfusion seem extremely easy.

Antrita

[shelleyk482]

You can expect the FDA to visit at least once every 2 yrs. They will look at everything you do in the blood bank. The biggest thing to remember is that your written procedure MUST match what you are actually doing and your procedure MUST match manufacturers directions unless you have extensive data to support not following manufacturer's instructions. This sounds easy in theory BUT in practice it can be a nightmare. There is no wiggle room for missing a weekly review (if your SOP requires it), or a late pipette validation, etc. FDA inspections are unannounced and extremely thorough; they tend not to be educational (at least in my experience), they are more punative in nature.

I have spent more than 20 yrs in FDA registered/licensed facilities and am very happy not to have that to worry about now. I fully realize that even though the facility I am in is not FDA registered/licensed that they could choose to come visit if they so desired, but the likelihood of that happening is very small since they are having a hard time keeping up with the facilities they have to inspect.

[Malcolm Needs ☆]

It is the word "punative" that worries me.

This is exactly what these inspections should NOT be, but they seem to be like this on a regular basis in the UK too. Then, instead of you learning and improving the service as soon as possible, you spend a whole lot of time explaining things to your own Quality Department.

:rage::rage:

[Antrita]

I was hoping they might leave me alone since the exchange transfusion is the only thing we do that requires FDA registration. I see this is wishful thinking on my part.

[kate murphy]

The FDA's focus is on the products that you produce. They ususally do not look at patient testing. They look at qualifications and competency of staff, and all QC and storage of blood/components to make sure the product is safe and efficacious. In 25 years of blood banking, I've only had one FDA inspector that I felt was unreasonable. If the only product you're producing is recon WB, your inspection should only be a few hours at most. The "fear factor" had been that FDA was unannounced - but in this age of unannounced CAP, AABB and Joint Commission, that's no longer a big thing. If you do not have donors, AABB and CAP are much more thorough than FDA.

[Antrita]

Thanks, that makes me feel much better. I have enough going on right now I don't need FDA fear lurking over my shoulder.

[L106]

Antrita -

Oh yes....You can expect to be inspected once you register with the FDA. I think shelleyk482 explained things very well. Unlike Kate Murphy, I have found most FDA inspectors to be more "thorough" than AABB, CAP, or JCAHO.

[shelleyk482]

I'm not trying to be an alarmist or negative, but I have not had the good experiences that Kate has had. In a hospital setting in which we washed RBC's and irradiated, whenever the FDA came in to inspect they looked at everything- testing, products, QC, maintenance, etc. Each inspector I've dealt with (I've tried to count and I think there have been 7 or 8 different inspectors through the years, in different facilities) has taken the SOP and sat down with at least one of my techs and watched as they did the testing to assure that the testing (# of drops, incubation period, # washes) etc. matched what was in the SOP. The inspector normally talks to different bench techs asking the same question in several different ways to make sure that the same answer is given. They have looked at all of the equipment validation, calibration, maintenance (to include pipettes, refrigerators, platelet incubators, MTS centrifuges, etc) and all log sheets.

Don't get me wrong, FDA inspections are manageable as long as you are always prepared. CAP & AABB give you a specific timeframe so you kind of know when they are coming. I've had FDA in 6 months before and up to 8 months after I expected them. If your SOPs match what you actually do & your documentation is complete, legible and thorough, you should be fine. Make sure you are up on the CFRs that relate to BB and make sure that your staff has periodic cGMP training. I would not count on the fact that the inspector will only look at those activities directly involved with the reconstitution of the whole blood; the FDA finds a way to tie all BB activities into the manufacture of the product.

This is one of those situations in which "you hope for the best and expect the worst". I truly hope that my experiences have been the exception and not the rule and that your inspections are like what Kate has related.

[Townsend]

Were any of you at the AABB meeting in New Orleans?

I attended a session "Ask the FDA" where this exact question was addressed - "does the TS that performs reconstituted whole blood only rarely need to be FDA registered?" They were very clear in they're response - YES! According to them, it does not matter how often you perform this component preparation; it is manufacturing a blood component.

The other thing that was brought up at the session was - "if your TS only performs this on such rare occasions, how do you determine that you're staff is competent in the procedure?" If anyone has any ideas how to maintain staff competency on rare procedures like this, please speak up! This was never addressed in any of our inspections (AABB, CAP, or FDA), but that doesn't mean that it never will be.

[Antrita]

We are not training every tech that works in the Blood Bank the exchange transfusion procedure. Is it acceptable to add on my exchange transfusion procedure to call the lab manager of the blood bank supervisor when one has been ordered? Should I list the technologists that have passed competencies on this procedure?

[Mega Tech]

ow I check If the final volume and hematocrit is within 5% of the order?

Thanks