Kip Kuttner

...Also perhaps the “numbness” was related to tongue swelling related to the allergic reaction.

There are many plasma proteins that can cause allergic reactions. Transfusing washed cellular products frequently prevents additional reactions. In addition, there have been several case reports of a donor consuming an allergen (peanut butter is classic) before donating. The recipient who is sensitive subsequently has an allergic reaction. One that comes to mind was well documented in the NEJM. And of course don’t forget the controversial IgA deficient patient allergic reactions.

Your institution will still need to file an eIND

You would need to research available studies or file your own eIND. Approval can take as little as 4 hour I am told. Then you would either collect it yourself, or work with you blood supplier to collect appropriate donors. Requires excellent communication. You can only use it for your study. It is not an off-the-shelf product.

Really sick patients needing ECMO will use blood. I don’t have a way to gauge the utilization at this time though. All the best.

Platelets are in adequate supply largely due to hospitals (in my service area) enforcing restrictive transfusion measures and postponing elective surgeries. Most blood centers except in New York, Washington state, and California are treading water with respect to RBCs. As usual Rh neg units are in short supply. Most of the hospitals in my service area are also freeing up beds to treat respiratory infections. These will require fewer transfusions, although patients needing ECMO are of concern. Looking ahead, it is difficult to predict what will happen. This is a long term event. My current concern is that blood donors will be fatigued 3 weeks from now and avoid giving blood. That is what happened after 9/11. It could be that you might need that unit of O neg on your shelf 42 days from now. In my opinion the goal is to provide blood for everyone who needs blood. Measures to restrict are prudent (and the literature indicates this is good medicine). After this is all over and we are criticized for being too conservative, but no one died for lack of blood, I can live with that.

Absolutely correct.

There are many facets to this question. I would think each institution has a disaster plan. It is an AABB requirement and I am sure a requirement for many other accreditation firms. From the blood supplier point of view: About 60% of the blood we distribute comes from mobile collections. Businesses, churches, schools and so forth permit us to hold collection events. If the local health departments discourage "gatherings" or even isolating parts of a community, this will adversely affect the blood supply. While the FDA encourages blood donation, the local messaging is what really matters. Isolation of well donors has already happened in places like Seattle and New York and is reducing the blood supply. Will the virus penetrate the population such that blood donors become unwell? This is hard to predict but look at Italy. Also the duration is difficult to plan for but with China it has taken about 31/2 months for the number of reported cases to fall. One might hope that different parts of the country are affected at different times permitting the movement of blood from one region to another. However given the mobility of the population it is possible that multiple regions are affected simultaneously and movement of blood is not possible. Hopefully, blood suppliers have begun to communicate with their hospital customers regarding the state of the blood inventory and the future ability to collect blood. From the hospital's point of view, what would happen if the supply became critical? When would you consider postponing elective surgeries, or rationing blood. Would you consider issuing splitting a whole blood unit in half and making that the "dose" in order to extend the supply (what makes the red blood cells harvested from a 450-500mL of whole blood a dose?) When do you start rationing blood/platelets? What about those transfusion dependent? do you divert those whole blood units intended for trauma patients to the chronically transfused. What happens if the hospital is overrun by those with respiratory illness like is happening in Italy? What about unwell staff? Will there be enough well to run the institution? I understand in Italy, administrators are transporting patients and pathologists (like me god forbid) are working in the ER . Are you sure there is an adequate supplies in your supply chain chain for each of your supplies/reagents so you can carry out business as usual? Silly things like hand sanitizer and toilet paper, gowns, gloves are already at a premium in certain parts of the country. I am mostly curious about your response to different levels of blood availability. How do you decide to post pone surgeries. After that should transfusion demand outstrip the supply what do you do and what is the trigger for implementing the action. Thanks Blood Industry Joint Press Release for Website - final 3.12.20.pdf

What are your institutions doing in the blood bank to prepare for the COVID-19 challenge?

Cliff, thank you for your kind remarks. I think We are in this together to take care of patients. What ever we can do to do the very best care we can in spite of the limitations is the approach we should take. Working together we can do that! Review Donor exclusion factors US Transfusion 0120.pdf

David and Cliff, I appreciate your frustration. Blood suppliers are well aware of the critical nature of their products and cringe each time they are compelled to supply less than the request number of units. Does your facility have an active part in the acquisition and stewardship of these DONATED gifts? I would think working with your supplier to find a way to increase the available inventory would be of benefit to all. For example does your facility help publicize blood drives and or encourage staff to donate. Does your facility hold successful blood drives? Do you monitor the utilization of especially precious products. I cringe when I hear an O neg about to expire went to a non-Rh neg donor in order that it not be "wasted". If an Rh positive unit would have worked, the unit WAS wasted because I bet somewhere in the system is an Rh negative recipient waiting for that unit. The literature suggests that 50% of the time this is how Rh negative units are allocated. Please try to import Rh negative units on the open market. At a meeting today one of our customers commented that to get Rh negative units they would need to purchase proportional equivalent number of non Rh negative units. So for example if you want to import 7 0 negs you would need to accept 93 Rh positive products. And this is the experience of the blood centers. I think your accountants would fuss if your attrition doubled from the extra blood you had to take. The low titer group O whole blood will take a toll on the availability of O positive blood. Because the expiration date is 21-35 days depending on the anticoagulant we will be approaching O positive donors more often to meet trauma resuscitation needs. This is the only business I can think of where the Product is voluntarily given by someone who will never know the good deed they did. Unlike product manufacturers, we cannot go to a plastics company or a drug company and ask them to just increase their production to adjust for changes in utilization. We do not PAY blood donors. We try to convince them blood donation is an honorable thing to do...and oh by the way we will give you a t-shirt. As a result we are not supplying a commodity, although blood centers are treated like vendors and are compelled to bid against each other producing ever slimmer margins. Think about whether you would want to issue blood that said PAID DONOR on the bag. Historically this has not worked too well, but it might be a way to increase donor participation. I suggest, rather than blaming the blood supplier, opening a dialog with them and being prepared to do some work on your part to help improve the blood supply would be more productive. No one wants patients to die for lack of an appropriate blood product when transfusion is indicated.

With attention to blood utilization, the overall red blood cell usage has gone down. Consequently blood suppliers have had to pair down the number of overall units they collect in order to avoid out dating products. Since we are drawing a population, the proportion of desired units in that population (All Rh negs and all group Os) has not changed, but the absolute number of the desired we can acquire units has dropped. Transfusion practices are still demanding nearly the same number of desired units as before blood utilization practices were implemented. About half of the Rh neg units distributed go to a non-Rh negative recipient, often because hospitals do not want to "waste" them. Perhaps if before making that decision to transfuse the blood bank contacted the blood center and asked if there was an immediate need to transfuse an Rh negative unit to an Rh negative recipient, we could better utilize the resources we have. Also I believe the merging of blood centers has contributed to the problem. Where the community blood center was usually able to manage the blood needs of the local hospitals, many are selling blood by contract to facilities miles away. This has decreased the amount of ad hoc blood available for export. The "low-titer group O" craze is also taking a toll because of the demand for repeat donors to fulfill the need to have Whole blood units with a 21-35 day out date, available for emergencies. Most blood centers are trying to recruit blood donors by blood group now in order to avoid out-dating Apos and Bpos units. This means that Rh negative and group O donors are approached to give 2-3 times more often than donors of other blood groups. The desired donors are complaining that they are being approached to give red blood cells too frequently and are starting to ignore our requests. All of these issues (and perhaps others) are contributing to the nation wide blood shortage of the most desired units. Importing products is also difficult. If they are available at all, did you know that in order to import four group O negative units a blood center might have to also purchase 50- 100 group A Pos units? Platelet utilization seems to be increasing. Where do platelet donors come from? Usually whole blood donors. Sometimes the blood center needs to decide whether to take a group O product or obtain a platelet product based on the needs of the day. Thank you to those who are excellent stewards of the products you receive! Blood centers are not shorting you because they are incompetent. Frequently it is extremely difficult to obtain the most desired products any where at any price. You can help your blood center serve you by being honest with your inventory.

With regard to PI with platelets, it is true you do not need to test the PI products but Babesia testing still needs to be done for RBCs collected in the 13 states of interest. Regarding test strategies, some hospitals,eg Johns Hopkins, has opted to do secondary bacterial testing on day 4 rather than the PGD test. Attached is a recent study covering the cost effectiveness of the approaches believed to be acceptable by the FDA. However, as noted the Guidance is not Final. This paper is a good starting point though. platelets Cost effectiveness methods bacteria testing Transfusion 0419.pdf

Because your blood counts will generate "patient Data" they fall under CLIA. Proficiency testing, competency assessment, training, and operator qualifications all apply. You can meet the requirements by having a qualified laboratorian general supervisor, oversee all of the instrument maintenance, calibration, linearity and QC review. The laboratory Director will need to follow some of these things as in traditional patient-based lab. Who will be your "CLIA assessor" for this activity, AABB, CAP, Other? If you are going to be AABB accredited then AABB will assess your operation against the CLIA regulations. The laboratory Director can be responsible for ordering the CBCs. However if this research is clinical, the physicians sending their patients should complete the orders. All of this should be specificed into your research protocol and IRB submission.

In response to LabIon: 1) Currently, the most experience with Low titer group O whole blood is in massively bleeding trauma patients. There is ongoing investigation to see if this product can be used in massive obstetric bleeding, cardiac surgery or other. It is important to remember that the utilization of this whole blood came from military experience. In addition much of the Whole blood used was group specific and warm. This is because refrigeration in some theaters is non-existent. the military does HIV, HCV and HBV testing on all service people periodically (every 3-4 months) in order to prevent transmission of these bugs for "walking donors". Hospitals are providing cold stored whole blood. 1.a. Adults at this time. experience is limited. 2) Titers are for anti-A and anti-B. The titer should be decided with the imput from the traua team, pathologists and the transfusion committee. 1:100 seems fairly common. The actual procedure for titration has not been standardized though. In addition some use 1:256. If you like history and references try : Tisdall LH, Garlane DM, Szanto PB et al. The effects of the transfusion of group O blood of high iso-agglutinin titer into recipients of other blood groups. Medial Corps, Army of the United States, from The army Whole Blood Procurement Service, New York, NY. https://academic.oup.com/ajcp/article-abstract/16/3/193/1761149 3) Whole blood can only be collected in bags with CPD (21 day expiration) or CPDA-1 (35 day shelf life). If interested in getting the biggest platelet response, it seems that platelet function drops significantly after day 14 of storage. 4) There is only one FDA approved leukocyte reduction filter that "spares" platelets. One of my colleagues has looked at platelet function following filtration with these bags and thinks that they are damaged by the filtration process, thus uses unfiltered units. Others do leukocyte reduce. Your mileage may vary. 5) Because you are not releasing the WB for transfusion until infectious disease testing is complete the unit needs to be stored at 1-6C. Use of this product is in its infancy. Stay tuned for new developments. Hope this helps.

I agree with Dr. Blumberg that pathogen inactivated platelets are probably safer than the "cultured" platelets and that the psoralin compound used in the process currently approved by the FDA crosslinks DNA/RNA thus preventing proliferation of most organisms and WBCs. However, to my knowledge the FDA has not given blessing for pathogen inactivation to supplant irradiation yet. Reading a copy of the "prescribing information" from Cereus would answer this question. However, it is expensive, $150-$200 premium on the current cost of the products. It is not yet approved for pooled platelet concentrate products. (six-pack) It is not yet approved for three products collected from a single donor (triple product). It is not yet approved as a 7 day product. There is about a 5-6 % decrease in the donors that qualify for giving two or three products at a time. This is because the pathogen inactivation process decreases the platelet count by 5-6%. This means that blood centers will need to replace this number of donors in order to keep up with current product demand. There are some who suggest the platelet efficacy of these products is diminished at as the product approaches day 5. Whether or not this is seen clinically, I do not know but this would have a bearing on whether or not the product will be approved with 7 day out-date labeling, There is a third option that can be entertained by the providers of these products. That is "delayed high volume culturing". This process makes it standard to obtain both aerobic and anaerobic cultures from each product. This process has been used quite successfully in Great Britain to interdict contaminated platelet products. I understand this process would be approved for labeling the product with a 7 day expiration date, without the need for the consignee to do point-of-release testing (Verax). I believe it is important for hospitals to discuss the product desired with their blood supplier. Opening the discussion now will make for an easier transition when the guidance becomes final. We expect to hear from the FDA on this topic later this year.

I noticed that in my last post, I was typing more slowly than I was thinking. In the US it is about 50 transfusions for every 1000 people in the US and 33 per 1000 in Canada. I apologize for the errors.

Hello, Here are a few suggestions that have served me, and our phlebotomy staff well over the years. We do therapeutic phlebotomy at the blood center (all sorts of diagnoses). When you prepare for the phlebotomy identify the select the best vein (obviously). The median cubital vein is usually most preferable because, in general, you will have less risk of inadvertently injuring a nerve. The basilic vein is a danger zone because of the nerves in the area and proximity to the brachial artery. Once you have a good understanding of how the vein travels, visualize the layers of tissue the needle will go through before striking the vein. Skin, subcutaneous fat, fascia, vein. The amount of each layer will vary with the physique of the patient/donor. Try to mentally picture the lumen of the vein being entered by the needle. Insert the needle at between 15 and 30 degrees from the skin. Normally and with experience you will feel increased resistance as the needle enters the vein and something described as a "pop" as the needle glides into the lumen of the vein. The 15-30 degrees is important because it gives you some leeway with the needle. It stays longer in the lumen as the needle advances, before going through the opposite wall of the vein. As the medical director of a medium size blood center I have seen my share of hematomas and they are usually caused by traversing the vein. In addition, with those big juicey veins, a frequent mistake is applying the tourniquet too tightly. this causes blood to leak from the insertion site at the side of the needle because the pressure in the vein exceeds the flow rate of the needle. Another bothersome event is the valves inside the veins, especially on larger veins, can cover the bevel of the needle. You will swear you are inside the vein, get a flash of blood and then nothing. Occasionally the leaflet can be dislodged by rotating the needle to the right or left. NEVER redirect the big needles. I demonstrate how much damage can be done by filleting a pork chop with a whole blood phlebotomy needle. My personal best time is 15 seconds to separate the meat from the bone. All the best

What I have been seeing is that the bulk of our donors donate 1-2 times per year. The last time we looked at the donor frequency it was less than 2, 1.3 time per year I think. I implemented a program whereby donors without a passing hemoglobin level were deferred 56 days rather than the usual 1 day at most centers. The blow back from the donors was phenomenal. Quite a few , especially women were shocked that I wanted them to wait for an extended period before their next attempt. Before I could see if there was any difference in deferral rate (the hope was that by decreasing the inter-donation interval the number of hemoglobin deferrals would fall) administration pulled support for the project. Surprisingly I suspect there is also an iron deficiency problem in platelet donors too. For some of them it is because they concurrently donate red blood cells with a platelet donation. In the platelet only group I suspect it is because they have borderline iron stores to begin with. They donate frequently enough that the volume of blood taken for samples is enough to put them into a negative iron balance. I can see the hemoglobin fall over time. Fortunately I am able to detect these donors and write them a letter asking them to be evaluated and if indicated take an iron supplement. Regarding high school donors, many blood collectors only visit a given HS 2x per year. At least this is our approach. Recruiting donors is tricky. As the saying goes, If it were easy to do, everyone would be doing it. However with proper blood management in hospitals, the demand is going down. This will make blood centers more selective about the drives they choose to run. At least is has had that effect on our center. Nationally we are at about 50 transfusions per person in the US. Canada is at about 33 transfusions per person. So thee is a lot of room to fall still.

I agree with everything that has been said. We do need to take better care of or donors. However as with most issues where people have trouble doing the right thing, money is involved. Doing A ferritin on each donor can add $6-$7 per donation. Perhaps it can be done selectively, for example on those donating more that 2 times per year, but this is labor intensive in the setting of a community blood center. Administering iron replacement tablets to donors is also a possible solution. We have seen that as little as 19 mg of iron is effective at reversing the iron depletion effects of blood donation. The cost of acquiring the iron supplements and administering such a program also incur additional costs that would need to be added to the unit of blood. There would also be benefits from reduced hemoglobin deferrals, but they are difficult to quantify. Another way to address this is to increase the interdonation interval such that men donate ≤ 3 times per year and women ≤ 2 times per year. Mayo in Rochester has tried this approach. This works for them because they supplement their blood supply with blood from another provider and have been able to manage the decrease in units. All donors must have a 38% HCT or 12.5 gram HGB soon to go to 39%/13 for males in the US. However, these numbers do not correlate too well to the donor's iron stores as predicted by ferritin levels. So there are solutions. However for those of you in the hospital setting, what price increase would your administrators accept in order to help your blood provider take care of their donors in an extremely competitive market? Finally, I am wondering why we are just now recognizing iron deficiency in blood donors now? Is it because we are looking for it and it has always been present, or is it something else, like a change in diet. Is the bioavailability of iron in our diet so different that we more easily become anemic? If 60% of blood donors are anemic before they even start donating blood, that suggests an iron availability problem in our environment...... Decreases in cast iron cooking pots, decreased red meat, fruit harvested when it is green, more processed foods... I wonder if these may be contributing to the iron deficiency. Some years ago high iron levels were supposed to be associated with heart disease; are people purposely choosing diets to reduce iron uptake?

My understanding of this issue is that when a "weak D" reaction (ie 2+ or less) is obtained the reaction needs to be investigated further to distinguish whether the patient had a subtype of D that is I, II, or III vs IV, V or VI. Subtype I, II, III can be considered Rh +, would not need RhD immune globulin, and could receive D+ RBCs. Subtypes IV, V, VI would. If the donor is any other D variant then clinical judgment would need to prevail regarding the necessity for either RhD immune globulin or D+ blood. For me the issue is regarding the outcomes. Would the patient outcomes be better, worse or the same after going through this exercise? Right now it seems that there is another branch in the clinicians decision tree, and another place for an error. I believe that one presentation suggested this process could free up about 50,000 Rh negative units annually in the US. Regarding Molecular testing in general, I think that it is a wonderful tool. As it pertains to this specific problem I am not sure it is cost effective.

In the journal article John Holcomb, MD et al, Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients with Severe Trauma. The PROPPR Randomized Clinical Trial. JAMA 2015;313(5):471-482, the 1:1:1 refers to the dose of plasma, platelets, and red blood cells used. For the study, a dose of platelets for was defined as 6 platelet concentrates (derived from whole blood). This definition was necessary so as to accommodate platelet products from single donors collected by apheresis and pooled platelets products since in some areas apheresis derived platelets are in short supply. Just in case you might be wondering about the conclusins drawn in the article, in the abstract the authors state: " Among patieints with severe trauma and major bleeding, early administration of plasma, platelets, and RBCs in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality and 24 nours or at 30 days. However, more patieints in the 1:1:1 group achieved hemostasis and fewer experienced death from exsanguination by 24 hours. Even though there was an increase in plasma and platelets transfused in the 1:1:1 group no other safety differences were identified between the 2 groups."

Another point of concern, for me is, when antibodies are made due to a first time antigen exposure IgM class antibodies appear first. When working up a prenatal, how do you know that the anti-M IgM just found is not due to a first time exposure and the antibody that follows in 8 or so weeks will not be a clinically significant IgG?

Actually, it seems that the OB folks in our area read about a baby developing HDN from potent anti M.. We have been asked to distinguish between an IgG and IgM anti-M to decide how to proceed with the serological evaluation of the pregnancy. In our case DTT treatment has not eliminated the reactivity at IgG. Thus the concern for a mixed IgG/IgM antibody. I was thinking that our anti-IgG reagent was made to the determinant on the Fc region of the IgG and should not react with IgM monomers formed after DTT treatment that might be hanging on to the RBC membrane after washing and the IgG reagent is cross- or non-specifically reacting. Strange things seem to happen when the antibodies don't read the textbooks. Another possibility is that the IgM was not completely disassociated by the DTT and there is residual pentamer on the RBC causing the residual reactivity. I have rarely seen a 4+IS reaction with an anti-M. When DTT treated, 1-2+ reactivity disappears in our lab. So we are going to cook the antibody a little longer in DTT. Thanks in advance for any other suggestions. Update: Cooking longer (2 hr and 3 hr) did not result in negative reactivity. It is 1-2 +. It seems to me this is a mixed IgG/IgM anti-M antibody so I guess I will recommend serial titers to OB.