The following two questions were submitted to the CBBS e-network for discussion based on the following clinical case. A physician ordered washed cells for what he called a "micro-premie" (presumably a very low birth weight premature infant). The ordering physician was worried over the potassium levels in a unit of any age, even a fresher unit.

Question #1. What are your opinions regarding the ordering of washed red cells for premature and low birth weight neonates to avoid the risk of transfusing excess potassium?

Question #2. What do you or your hospitals consider "fresh" for neonatal transfusions?

Before distributing these question to the network, I previewed these questions with two experts in neonatal transfusion practice. Here is what these experts had to say:

The first expert said that there have been several papers published that support the conclusions of an article published in the Am J Clin Pathol 1997 Apr;107(4 Suppl 1):S57-63, entitled 'Practical issues in neonatal transfusion practice.' In that article, the author stated that small premature infants frequently require transfusions of blood components, particularly red blood cells (RBCs), during the first weeks of life. Although great efforts have been made during the past few years to optimize the transfusion of blood components to these tiny patients, several questions have not been definitively answered. Accordingly, transfusion practices vary among neonatologists. The purpose of this article was to assess the available data critically. The findings indicated that stored RBCs can be transfused safely into premature infants to diminish donor exposures. It was also found that leukocyte-reduced blood components can be used to prevent the transmission of cytomegalovirus; thus, cellular components do not need to be obtained exclusively from donors negative for antibodies to cytomegalovirus. However, gamma-irradiation of cellular blood components cannot be justified for all neonatal transfusions. Obviously, as new information is reported, these findings may require revision. According to this expert, in the USUAL small volume setting, transfused K⁺ is not a problem. Finally, this expert says that his institution does not have a definition for 'fresh RBCs' -- however, the maximum storage age for a blood product MUST be defined differently for different clinical circumstances.

The second expert said that if you calculate the amount of free potassium infused with each aliquot of RBC, you will find that the amount of free potassium in an aliquot of older, irradiated RBC is about a "maintenance" potassium dose. It is nowhere near the size of a therapeutic potassium bolus. Therefore, potassium is not a concern with aliquot transfusions. Potassium can become a concern in massive transfusion, however, if the amount of free potassium infused is significant. Even in massive transfusion, however, potassium-depleted red blood cells will re-absorb the potassium after transfusion, and potassium will also be absorbed by the cells of the transfusion recipient. The patients most at risk of hyperkalemia during massive transfusion appear to be those whose cells are unable to absorb the potassium bolus, i.e., those with underlying acidemia and hyperkalemia. This expert was not familiar with any literature that compares premies to larger children as to their ability to absorb potassium. The expert also commented that at her institution they recommend less than one-week old blood for exchanges. Her institution used to recommend blood less than two weeks old, if possible, for neonatal surgeries, but they do not do this any more because it was impossible to enforce. In meetings with pediatric anesthesiologists, they were only concerned about two patient populations - the pediatric liver and the kidney transplant patients. For these patients, the pediatric anesthesiologists have requested non-irradiated blood, as they feel that the potassium load can be clinically problematic in these patients. In the liver patients, apparently, the ischemic liver cells can release free potassium when the liver is manipulated, and the anesthesiologists want to minimize the additional potassium load in transfused blood. The liver transplant surgeon agrees that hyperkalemia is a problem during liver transplantation but disagrees that the transfusion plays a clinically significant role in this problem. The kidney transplant patients may start out hyperkalemic if they haven't been dialyzed recently, and therefore have less ability to absorb the free potassium in transfused blood. Washing is usually not a realistic option for surgery patients because we cannot predict how many units the patients will need, and if they suddenly start bleeding during surgery there is not enough time to wash units.

1. An e-Network member suggested the following additional considerations:

1. the site of the transfusion - if blood is given centrally or directly into the heart, there may be problems even with a small bolus of potassium in the transfused aliquot whereas peripheral administration should be much safer.
2. the temperature of the blood - when blood is cold, especially when bolused centrally, the risks increase and this may add to the potential problem with increased potassium
3. the presence of citrate - the potential adverse effects of hyperkalemia, according to Mollison, are made worse with citrated blood; and this would be made worse, once again, with central blood administration.

2. And here's another:

At our hospital, we transfused blood up to the date of expiration (35 days for non-irradiated CPDA-1 units and 28 days for irradiated units). We do not routinely irradiate units but do use significant number of directed donor units from relatives which are irradiated. I have gone through the calculations of the expected K⁺ load in small volume transfusions and the amount of K⁺ is about that a neonate will receive for daily maintainence. We only worry about K⁺ loads for large volume transfusions and in those instances use blood 1 week old. Larger volume transfusions are rare in our institution as compared to small volume transfusions.

3. And a third:

A study was done with the group at Children's Hospital in San Francisco back in the early 1990s when people were really focusing on reducing donor exposures in premature infants. That study demonstrated some interesting results in regard to potassium. Because the focus of the study was reducing donor exposures, the potassium issue is buried in the "Results" section. The title of the paper is "Reducing blood donor exposures in low birth weight infants by the use of older, unwashed packed red blood cells" J Pediatr 1995; 126:280-6. The study group comprised neonates under 1500 gm at birth who were randomized into groups receiving either aliquots from a washed, fresh 'common-unit' type O unit or aliquots from a dedicated, type-specific, unwashed unit used up to outdate of the unit. As the data show, the number of donor exposures per neonate was substantially lower in those receiving red cells from a dedicated unit. The study also looked at serum potassium levels immediately before and after transfusion and potassium levels on the blood from the tubing to ascertain the level in the transfused units. There was a mean increase in the serum potassium concentration of 0.14 mmol/L (0.14 mEq/L) with unwashed, irradiated blood compared with a net drop in the potassium concentration of 0.15 mmol/L with washed red blood cells. There was no correlation between the age of the infused unwashed red blood cells and any of the changes in the infants blood values. The only clinically significant change in serum potassium in an infant post-transfusion occurred in the control group in which an infant receiving washed common-unit cells had a serum potassium level drop transiently to 1.8 mmol/L.

ADDENDUM Sept. 1, 2000, submitted by a fourth network member:

4. Years ago, when this member was thoroughly researching this topic, she recalled seeing literature in which not only is there a risk of hyperkalemia from transfusions of stored blood, which, as expected would be an immediate problem since the potassium is free in the supernatant, there is also the possibility of hypokalemia which would result if potassium was sponged up by old RBCs. This is why this member believes that in situations where potassium homeostasis is brittle, the blood should be both washed and as fresh as possible. This will avoid the possibility of subsequent hypokalemia.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator