A blood banker wrote that she has concerns about how best to handle complications of citrate toxicity in otherwise health allogeneic stem cell donors. Specifically, is calcium administered? If so, in what form and dose? Are any other medications or treatments routinely administered, such as magnesium or potassium? The inquiring blood banker says that her facility does not have the capability to perform electrolyte testing in house and they are hoping to make the donor as comfortable as possible without increased risk.

The replies that follow were submitted in response to the questions shown above. It is interesting to note that experiences with citrate toxicity in allogeneic stem cell donors seems quite variable between facilities.

1. A blood banker from Virginia wrote that her facility collects allogeneic stem cells from (related, currently) healthy donors. They do not routinely administer Ca, Mg or anything else IV to these donors. The donors can be given TUMS for tingling, etc. They did have one
recent donor (everyone wonders if she was normal or not) who actually required IV calcium. The donor was complaining of the usual tingling and getting lots of TUMS. The machine was turned down, but the donor got progressively more symptomatic. (The responding blood banker says that she didn't witness this, but) the donor actually began to have a carpopedal spasm with tremendous twitching The donor ended up on a calcium drip. Her ionized calcium was very low at the onset of therapy and went up with treatment, but only very slowly. Bottom line, problems when collecting allogeneic stem cells are unlikely, but you have to be prepared to respond when they do arise.

2. A blood banker from Pennsylvania wrote that his facility collects autologous and allogeneic peripheral stem cells in an outpatient setting which is located within the hospital. They routinely administer KCl and calcium by IV (drip or push), and magnesium as needed, and they have been known to give IV antibiotics, steroids, and blood components, but not as a routine. They also give TPA for clogged central lines if necessary. They collect stem cells from both adult and pediatric individuals. Obviously, all of this becomes problematic in a blood center setting, but not impossible, as it would require a dedicated and knowledgeable staff, an administrative structure that will provide the necessary infrastructure, and attention to special details such as how to handle emergent situations. The responding blood banker's nursing staff is happy to share ideas and knowledge with others. The responding blood banker (Dr. Ronald E. Domen, Medical Director, Blood Bank and Transfusion Medicine Director, The Milton S. Hershey Medical Center) said any e-network member can call his service at 717-531-3977 to discuss this issue.

3. An former AABB president wrote that "years ago we did some studies of ionized calcium, EKG changes etc. during apheresis The bottom line is that the changes are not readily predictable for an individual, even when adjusting for size, citrate dose etc. For the EKG the critical feature is change from baseline, NOT any arbitrary interval. However even for a given change the myocardial and conduction effect will also vary from person to person".

4. The medical director of an apheresis center in the Southwest High Desert in New Mexico commented that his center does about 750 procedures a year, including allogeneic stem cells. They routinely administer calcium gluconate (NOT calcium chloride) to their therapeutic apheresis patients AND stem cell donors. The typical order written by the attending physician will be to take 4 vials (40 mL) 10% calcium gluconate and add to 250 mL saline and then run at 70 to 140 mL/hour prn for signs of citrate toxicity. The stem cell donors usually run on the lower end of this spectrum.

5. A "new" blood banker (recently completed her fellowship) commented that her experience as a fellow in a fairly large donor center was predominantly with autologous stem cell donors. However, allogeneic donors were periodically collected. As a routine no Calcium other than 'TUMS' were used. Rates were slowed as necessary. This worked well most of the time. She makes the following observations: "I made a few anecdotal observations, regarding the allogeneic donors. In general they experienced more difficulty with citrate toxicity than autologous stem cell patients, often culminating in carpopedal tetany. This happened often enough for us to discuss the possibility of infusing calcium to these donors on a routine basis (although I don't think this was ever implemented). We did also note that when questioned many of the donors admitted to a recent history of dieting, using some form of diet aid (pills). It would be an interesting study if you could find enough subjects.

6. At a blood center in Sacramento they report using TUMS only, for the calcium repletion of allogeneic peripheral blood progenitor cell donors.  In general, their results have been very good, with no significant citrate toxicity. Also, other than Tylenol (for typical deep bone pain), they have not been using any other medications/treatments for these donors.

7. A blood banker from the Midwest said that he would refer the inquirer to a related article by Bolan CD et al. Comprehensive analysis of citrate effects during plateletpheresis in normal donors. Transfusion 2001;41:1165

8. A blood banker in Sacramento reported that they collect allogeneic PBSC donors from NMDP, as well as related donors for the UC Davis Transplant program. While the NMDP collections are shorter (10-14 Liters processed on each of 2 days), others involve processing 20-22 Liters, depending of the size of the recipient. Donors are encouraged to eat well before the donation and to have snacks with them (cheese, yogurt, and the like) We are very generous with Tums, and do not administer medications, or do any electrolyte testing. A very small donor may have to be collected slower than a very large one.

9. A blood banker in the Northwest USA submitted the following response to the question about administration of calcium gluconate during PBSC collections from allogeneic donors. He currently works at a blood center that has had a lot of experience with stem cell collections from healthy donors. They have had two instances where donors began exhibiting signs of citrate sensitivity early in the procedure and did not respond to decreasing the inlet flow rate nor TUMS. The Medical Director ordered 10 ml of calcium gluconate administered at 1 ml/min as a bolus. The donor immediately felt better and was able to continue with the procedure. The following day we had to do a second collection. In order to prevent symptoms, we administered calcium gluconate via a continuous drip through the return apheresis needle line. The concentration was 20 ml of 10% calcium gluconate diluted in 500 ml of NS. This was administered using a Buretrol for accuracy over the length of the procedure (approximately 3 hours). The donor tolerated the procedure without any signs of citrate toxicity. You may need to give more calcium depending on the donor's response and body size. As a small apheresis unit, they do not have any cardiac drugs, no EKG monitors and do not make it a practice to perform electrolyte tests on these donors. They have not encountered any adverse events and feel comfortable with our assessments regarding donors signs and symptoms of citrate sensitivity. Another point is that they are administering calcium gluconate which has one third the potency of calcium chloride. Another suggestion (if it is within their budget), is to use an I-STAT which would give you a rapid measurement of ionized calcium at the bedside.

ADDENDA Dec. 6, 2005

10. A Blood Donor Services Coordinator in Southern California wishes to add to this e-Network Forum discussion the following question regarding documentation of medications used on donors: "Are donor centers using individual physician orders, or SOP-defined standardized orders for the administration of TUMS (or ACD for that matter) during apheresis procedures? For those centers relying on SOP-defined standardized orders, does the SOP specify the frequency, dose, and symptoms required before giving the medication? Is each tablet that is taken by the donor documented, or is just the total amount taken documented?"

Please submit comments to the e-Network Forum.

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