Preventing/treating citrate complications during peripheral blood stem cell (PBSC) collection

A transfusion medicine physician in India has reviewed reports on preventing/treating citrate complications during peripheral blood stem cell (PBSC) collection in order to determine an optimal dose of calcium to be administered during PBSC/plateletpheresis procedures. At his hospital Transfusion Service in India, they have been giving 10% calcium gluconate added to 100 milliliters of normal saline as a continuous infusion run over 45 min-1 hour during PBSC collection. Normally the procedure lasts 4-5 hours and a typical patient needs 4-5 vials each administered in 100 ml saline packs. They have been doing at least one procedure per month during the last 7-8 years and the inquiring colleague cannot recall a single incidence of complication attributed to the aforementioned protocol. His concern is more with platelet pheresis donations. His staff feel quite comfortable to give 3-4 tablets of calcium (approximately 1g) and believe that donors do not have reactions because of this. He would like to know if any colleagues can share data (or published references) pertaining to the dosage of calcium to be given during platelet pheresis donations and/or therapeutic procedures. The ACD infused during the procedure varies between 250 ml – 350 ml in most instances, except in case of double SDP collection where it could go up. Donors are not checked for calcium levels before donation.

Editors' note: Colleagues might find the previous discussion, "Complications of citrate toxicity in otherwise health allogeneic stem cell donors" to be germane to the above question.

The following comments have been received in response.

ADDENDA Dec. 4, 2009

1. A respected apheresis researcher by the name of Susan Leitman, MD, who is working at at a large institution in Bethesda, MD, surrounded by an enourmous security fence (attribution used with permission) responds:
   
   "We agree with the inquiring physician that the administration of prophylactic continuous intravenous calcium is a highly effective and critically important component of the safety of PBSC collection, or of any large volume leukapheresis procedure. Our experience is that severe citrate toxicity, including tetany, is unavoidable at the high blood flow rates and citrate infusion rates used in these long procedures, unless some form of intravenous calcium is given. We have found that IV calcium infusion rates dosed to administer 0.6 mg of elemental calcium per 1 mL of ACD-A are optimal. This can be accomplished by adding six 10-mL vials of 10% calcium gluconate (each vial contains 1 gram of calcium gluconate salt, equal to 93 mg of elemental calcium) to 220 mL of saline. The final concentration of elemental calcium in this solution is 2 mg/mL. When this solution is administered at a rate (in mL/hr) that is 18 times the ACD-A flow rate (in mL/min), then the final dose is 0.6 mg Ca++ per mL of ACD-A. In a typical 70-kg adult who undergoes a 24-liter PBSC procedure at a citrate:blood ratio of 12:1, with an inlet flow rate of 85 mL/min, we will administer about 500 mL of this calcium gluconate solution over the 5 hours of the procedure. This sounds very similar to the algorithm used by the inquiring physician in India. We still occasionally see citrate-related complaints, and if they occur, we decrease the inlet blood flow rate by 10-15%, or increase the calcium infusion rate by 10-15%, or both. We do not routinely check ionized calcium levels during these procedures.
   
   Plateletpheresis procedures are run at a slower rate and involve much less volume processed, compared with PBSC collection, so that severe citrate toxicity is uncommon, though mild to moderate citrate effects are frequently seen. I do not know of any center that gives continuous infusions of intravenous calcium during routine plateletpheresis. Donor centers do not stock expensive programmable infusion pumps, and intravenous calcium should only be administered by a trained nurse. In addition, attachment of the calcium gluconate bag might disrupt the closed-system integrity of the apheresis kit. A randomized placebo-controlled trial of oral calcium carbonate given 30 minutes prior to starting plateletpheresis showed that a 2-g dose resulted in a modest improvement in citrate-related symptoms and laboratory parameters. A 1-g dose was ineffective, and a 4-g dose caused unpleasant GI symptoms.1,2 We recommend a 2-g oral calcium carbonate dose prior to starting apheresis in donors with a prior history of citrate effects and in those at higher risk (smaller women). This dose can be repeated based on symptoms during the procedure. The transfusion medicine physician in India is doing very well!
   1. Bolan CD, Wesley RA, Yau YY, Cecco SA, Starling J, Oblitas JM, Rehak NN, Leitman SF. Randomized placebo-controlled study of oral calcium carbonate administration in plateletpheresis: I. Associations with donor symptoms. Transfusion 2003 Oct; 43:1403-1413.
   2. Bolan CD, Cecco SA, Yau YY, Wesley RA, Oblitas JM, Rehak NN, Leitman SF. Randomized placebo-controlled study of oral calcium carbonate supplementation in plateletpheresis: II. Metabolic effects. Transfusion 2003 Oct; 43:1414-1422.

Submit comments to the e-Network Forum at enetworkforum@cbbsweb.org

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

W. Tait Stevens, MD
CBBS e-Network Forum Editor & Moderator

Elizabeth M. St. Lezin, MD
CBBS e-Network Forum Associate Editor & Moderator