Neil Blumberg

Another inspector who is a bureaucratic and clinically ignorant rigid thinker. My sympathies. There is no reason to document early infusion rates, and these vary by patient due to clinical condition. This is just a guideline and not a requirement, as the inspector would know if they had any bedside clinical practice experience. Just say it's a rough guideline, not a requirement, and clinical judgement will determine the infusion rate for each patient.

If the antibody does not react at 37 or antiglobulin phase, we would not recommend a blood warmer. Agree that in patients with cold agglutinin disease or hemolysis after exposure to cold, would use a warmer. Remember that our techniques in the lab routinely detect antibodies of no clinical significance. For one thing, we never centrifuge patients at 170g to enhance binding of red cells to antibody :). So on balance, unless you have an antibody of known clinical significance historically (antibodies in the Rh, Kell, Duffy, Kidd, S, etc. systems) and it reacts at body temperature, it's probably not significant. Cold antibodies of wide thermal range may be significant but usually not if they don't react at body temperature in vitro.

As you know a difficult question. The use of group O blood for non-O patients should be limited as soon as the ABO type is known, and ABO type specific given. There are some old admonitions to never transfuse type specific after X numbers of group O red cells or whole blood. This is nonsense, so do not follow this old precept. Give only ABO type specific as soon as possible. As for giving non-O blood to O patients when all other options are exhausted, I would only do this if death were imminent due to bleeding, not ever for routine transfusion. There are case reports of no hemolysis in such situations, including the one below from my original mentors from half a century ago. Accidental error but no consequences. But giving non-O blood to O recipients has the potential to cause rapid death in many instances. We don't know why there are such varied responses. Case Reports Transfusion . 1975 Nov-Dec;15(6):577-82. doi: 10.1046/j.1537-2995.1975.15676082233.x. Unusual response to ABO incompatible blood transfusion D H Buchholz, J R Bove PMID: 1198685 DOI: 10.1046/j.1537-2995.1975.15676082233.x Abstract Three units of group A blood were inadvertently administered to a group O recipient during surgery without evidence of hemoglobinemia, hemoglobinuria, hypotension, disseminated intravascular coagulation, acute renal tubular necrosis, or other signs and symptoms of transfusion reaction. The recipient had normal concentrations of IgG, IgA, and IgM as well as complement (C3) prior to transfusion and anti-A agglutinins titered to 64 (titer of 128 by the antiglobulin technic). Seventeen hours following the transfusion, 28 per cent of the circulating red blood cells were group A (equivalent to 475 ml of packed cells); they were eliminated by day 5 without evidence of hemoglobinuria, hemoglobinemia or hyperbilirubinemia. Anti-A titers (antiglobulin) had risen from a posttransfusion low of 4 to 4,096 by day 10. After treatment of serum with 2-mercaptoethanol, however, hemolytic activity which was first noted on day 5 was lost and the antiglobulin titer dropped to 24 which suggested that most of the anti-A produced in response to the transfusion was IgM rather than IgG. The anti-A titer had dropped to essentialyy pretransfusion levels and the majority of anti-A present was IgM by day 91. The recipient suffered no untoward effects from the transfusion and was in good health three months following the transfusion.

Transfusion has much more serious adverse effects than making an anti-D. Increases in infection, sepsis, thrombosis, inflammation and mortality for example. There are no data to my knowledge of long term effects of anti-D formation in patients not having future pregnancies. Most such patients come to the attention of the transfusion service because they have anti-D or simply because they are Rh (D) negative. They are then transfused with D negative blood if need be, in something like 99.99% of cases. The rare patient who gets Rh positive blood (trauma patients) do sometimes have increases in bilirubin, LDH, etc. and delayed or rarely acute transfusion reactions. These are bad for patients, so you are right, for these rare patients, the outcomes can be dire. But there few alternatives to transfusing Rh (D) positive blood to most patients in emergencies. And very few will have future transfusion reactions.

Depends on the distance from transfusion service to ED/OR. I assume you are not planning on having the cooler or refrigerator with blood in the ED on a routine basis, only when the mass casualty event occurs? Are you the only hospital in the area, or are there other hospitals with level I or II trauma capability?

It varies from no reaction to lethal hemolysis. Anti-D is not entirely predictable in causing severe hemolysis. But mostly bad stuff happens :). This is true to some extent for anti-A and anti-B, although these are more dangerous as they fix complement in vivo better than anti-D in general. Joe Bove (my original mentor) reported a case of a patient receiving multiple units that were ABO major incompatible with no reaction. Not typical, but illustrative of the variability.

Even without a transfusion reaction, the haptoglobin drops with transfusion of red cells. Lots of non-viable cells and free hemoglobin in many red cell transfusions. If you cannot see red urine, red plasma and a drop in hematocrit/failure to rise, it's not a hemolytic reaction. Haptoglobin plays almost no role in assessing hemolytic transfusion reactions, and, as mentioned, unless you measure it on the pre-transfusion sample as well, tells you almost nothing. LDH pre and post would be more useful in most cases. Don't bother with haptoglobin in most cases.

The rate of alloimmunization in massive transfusion trauma patients who receive D positive red cells appears to be quite a bit lower than seen in healthy adults exposed to D positive red cells many years ago in the original trials. Perhaps as low as 1-2%, not 40% as seen in healthy recipients of test doses.

We only use it for antibodies that are unlikely to be clinically significant (an example would be anti-M) if they do not react at 37 and antiglobulin phase. Sometimes you find an anti-M that reacts weakly at 37, but not antiglobulin phase, and the prewarm makes it disappear at 37. In most cases, we would then ignore the antibody. Just some additional information to make clinical decisions. We wouldn't bother for antibodies usually capable of causing red cell destruction at body temperature. A strong cold with broad thermal amplitude up to 37 would not be much helped by pre-warming, so we use other techniques such as auto-adsorption to make it "go away." Thus we don't bother there with prewarming, just as we wouldn't be interested in making an anti-C or anti-Jka disappear by prewarming.

5 ml/kg plus whatever amount is needed for the dead space, although they can flush that with crystalloid. One unit minimum perhaps. That's 15 ml/kg for a 1 kg premature newborn. Would suggest a maximum of 10 ml/kg. 5 unit pool would be about 75 ml/kg for a 1 kg neonate, a terrible over dose that would increase the risk of congestive heart failure due to volume, and thrombosis due to excessive fibrinogen and factor VIII in cryo. My advice is don't do that no matter how much your neonatologists want to do that. Potentially fatal. No possible therapeutic rationale.

My condolences to her family, colleagues and friends.

I don't think the AABB comments are evidence based. Washing with 37 degree saline is extremely unlikely to cause false negatives with clinically significant antibodies, and I'm unaware of any evidence that this is so. Any such antibody would be very low affinity to be washed away by saline at any temperature, and unlikely to have in vivo/clinical significance. As argued persuasively above by Malcolm Needs, anything that doesn't react at 30 degrees or above in typical serologic testing isn't going to cause clinical problems. Patients are neither at 30 degrees nor centrifuged :). Our serologic techniques are overly sensitive, in general, for clinically insignificant agglutinins. No need for cold panels ever, with rare exception, and more for intellectual curiosity than clinical decision making. Perhaps a mini-cold screen someetimes just to confirm you are indeed detecting a weak cold agglutinin in 37 degree testing, which disappears with prewarm technique. Like Malcolm, I've never seen a patient with an hemolytic reaction due to an antibody that disappears with prewarming, in close to 50 years of clinical practice. I know there are in vitro examples of clinically significant antibodies that weaken or disappear with prewarm, but I've never seen any clinical consequences.

In emergencies, we always accept verbal orders for transfusion. These should be followed up by a request documented in our electronic medical record, but that's after the fact. If you have a paper system, then the followup order is documented that way. There is a regulatory/accreditation requirement, which I consider bureaucratic, obstructive and useless, that these emergency requests require a signed release from the ordering practitioner, if the transfusion is not fully tested for the recipient.

Agree that a urine specimen isn't indicated for an allergic reaction, so no worries.

Here's one paper that involves extended cold storage of room temperature platelets. They actually seemed more functional. Xu F, Gelderman MP, Farrell J, Vostal JG. Temperature cycling improves in vivo recovery of cold-stored human platelets in a mouse model of transfusion. Transfusion. 2013 Jun;53(6):1178-86. doi: 10.1111/j.1537-2995.2012.03896.x. Epub 2012 Sep 24. PMID: 22998069. Background: Platelet (PLT) storage at room temperature (RT) is limited to 5 days to prevent growth of bacteria, if present, to high levels. Storage in cold temperatures would reduce bacterial proliferation, but cold-exposed PLTs are rapidly cleared from circulation by the hepatic Ashwell-Morell (AM) receptor, which recognizes PLT surface carbohydrates terminated by β-galactose. We cycled storage temperature between 4 and 37°C to preserve PLT function and reduce bacterial growth. Study design and methods: Temperature-cycled (TC) human PLTs were stored at 4°C for 12 hours and then incubated at 37°C for 30 minutes before returning back to cold storage. PLTs stored at RT or at 4°C (COLD) or TC for 2, 5, and 7 days were infused into SCID mice and the in vivo recovery was determined at 5, 20, and 60 minutes after transfusion. Results: PLTs stored for 2 days in COLD had significantly lower in vivo recoveries than RT PLTs. TC PLTs had improved recoveries over COLD and comparable to RT PLTs. After 5- and 7-day storage, TC PLTs had better recoveries than RT and COLD PLTs. PLT surface β-galactose was increased significantly for both COLD and TC PLTs compared to RT. Blocking of the AM receptor by asialofetuin increased COLD but not TC PLT recovery. Conclusion: TC cold storage may be an effective method to store PLTs without loss of in vivo recovery. The increased β-galactose exposure in TC PLTs suggests that mechanisms in addition to AM receptors may mediate clearance of cold-stored PLTs.

Short periods of time (<12 to 24 hours say) at refrigerator temperatures have no known deleterious effect on platelet transfusion efficacy, so I would use them as I would use any platelet component stored at room temperature. I routinely approve this at my own institution when this happens.

The fact is that we have little to no evidence that platelet transfusion of any sort will mitigate post-pump bleeding. This is expert opinion only that has driven this practice. What we have learned in the last few years is that platelet transfusion as currently practiced (ignoring ABO for one thing) actually increases bleeding and mortality in some clinical settings. I'd rather have some oozing than be transfused with platelets empirically, both as a patient and a hematologist. With life threatening bleeding and abnormal platelet function as measured by a closure time or TEG/ROTEM, platelet transfusion makes sense and has some data driven support. Oozing, no data whatever.

Sounds like total rubbish from both a clinical and scientific viewpoint. Another instance how the administrative/legal model of reality is undermining civilization :).

I should have added that I recognize that some cardiac surgeons transfuse platelets routinely post-bypass in the hope of reducing bleeding. I suggest this is a traditional practice without the slightest shred of evidence for benefit. Purely guesswork and expert opinion, for which there is now evidence of harm. So whether you give cold or room temp platelets probably doesn't matter as (1) there is likely no benefit to either approach, and (2) there is likely equivalent harm either way. So my short answer is it doesn't matter, but that platelet transfusion to non-bleeding surgical patients likely doesn't help, and may increase the risk of thrombosis, inflammation and reduced host defenses against post-operative infection.

Why are we transfusing platelets to patients who aren’t bleeding? More likely to harm them than help them in my view.

I agree with the procedures above. But these are basic urgent communications required of any clinical service, and I wouldn't characterize them as critical values, which are emergencies. Perhaps it's just semantics :).

We have no critical values in the Blood Bank and we have a cancer center that sees thousands of patients per month. And it is my recommendation that critical values be restricted to truly life threatening conditions that require treatment within minutes to hours (e.g., very high or low potassium). I would most definitely NOT have critical values for things like creatinine/BUN, liver function tests, MCV, white count, etc. Provides no clinically actionable information acutely, and wastes a lot of time in the lab and amongst practitioners.

I'd also add that none of the cell washers are FDA approved for washing platelets. We've been washing platelets on the 2991 for about 40 years :). I believe there may be a paper on using the ACP-215 to wash platelets but as yet we do not have any hands on experience. We have developed a manual method of platelet washing using a Sorvall centrifuge. If your volume isn't too high, you might consider a manual wash method. It takes a bit longer, but actually has higher recoveries (>90% vs. about 80-85% with the 2991). Folks will tell you that washed platelets don't work clinically and the count increment is Washed Tx Leukemia.pdfWashed Tx Leukemia.pdflower. The increment is indeed lower, but if you employ platelets that aren't ABO incompatible with the recipient and remove the supernatant, the clinical results are actually better than the clueless advice to give ABO major incompatible platelets routinely (e.g., group A to group O recipients). The PLADO study had a bleeding rate using this abominable practice of about 70%. Our bleeding rate avoiding infusion of ABO incompatible antigen or antibody is 5%, with or without washing. A fourteen fold difference. So by all means give washed platelets to patients with severe or recurrent reactions, or avoid infusion of ABO incompatible plasma, and, if you believe our randomized trial data, to improve the survival of younger patients with acute myeloid leukemia. References attached if anyone is interestedWashing AML Greener_et_al-2017-American_Journal_of_Hematology.pdf. Washing Review IJCTM-101401-the-clinical-benefit-of-washing-red-blood-cells-before-transfusion.pdf Washing AML Greener Am J Hemat AML Washing Supplementary Figures and Tables.pdf Jill's washing paper.pdf Plt Washing Vo.pdf

There is no regulatory nor clinical reason not to wash AS-3 units on the Haemonetics device. Just validate it for red cell recovery and hemolysis, comparing AS-3 with five AS-1, CPD-A1 or other units you can obtain from another blood center, if this makes you feel more secure. We wouldn't and won't bother to do so. The results will likely be identical. There is no material difference in red cell preservation issues with the various additive solutions and certainly no evidence of difference in clinical outcomes.

Hail and farewell.