Citrate Effects and Bone Density Changes in Serial Long-

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Approximately one million plateletpheresis procedures are performed each year in the U.S., including 3,500 in the Platelet Center of the Department of Transfusion Medicine, NIH. Healthy donors are eligible to undergo plateletpheresis and leukapheresis procedures as often as 24 times per year. During plateletpheresis, citrate anticoagulant is added to the blood collection pathway to prevent clotting in the apheresis device, and is infused into the donor during the procedure. Adverse effects related to citrate administration are common, and include acute hypocalcemia due to the formation of calcium-citrate complexes. Recent studies in our Department indicate that changes in serum calcium, parathormone, osteocalcin, alkaline phosphatase, and vitamin D levels are also present and may be sustained for up to 24 hours after apheresis. In addition to volunteer plateletpheresis donors, the NIH Department of Transfusion Medicine maintains a registry of approximately 500 leukapheresis donors, who provide components for in vitro research use. These research apheresis procedures may involve processing twice as much blood volume (10 liters) as is processed in a typical plateletpheresis procedure (5 liters). Thus during leukapheresis, the total dose of citrate administered to the donor may be twice as great as that which occurs during plateletpheresis. Leukocyte and plateletpheresis donors may undergo more than 100 apheresis procedures during the course of their participation in the donor program at NIH. Donors are encouraged to take oral calcium carbonate supplements before or during apheresis if citrate related symptoms occur or have occurred in the past. The impact of serial, frequent, long-term apheresis donations on total body calcium balance and bone density is unknown. In this study, we performed bone density measurements (DEXA scans) of the wrist, lumbosacral spine, and hip in three cohorts of NIH donors (1) 50 long-term plateletpheresis donors who have undergone at least 50 plateletpheresis procedures at NIH in the past 10 years, at intervals no greater than every 4 weeks (2) 50 long-term research leukapheresis donors who have undergone at least 50 leukapheresis procedures at NIH in the past 10 years, at intervals no greater than every 3 weeks (3) 118 age-, gender-, and race-matched whole blood donors, who have never undergone apheresis, as a control group for NIH apheresis donors, and (4) 21 community platelet donors who have donated at least 100 time, as frequently as every 2 weeks. Comprehensive laboratory evaluations of the effect of citrate administration on bone metabolism and body calcium and magnesium levels before and after apheresis were also performed. The data indicate that apheresis induces an acute increase in parathyroid hormone, accompanied by a reduction in osteocalcin, and an increase in c-telopeptide and vitamin D levels. Some of these changes persist for as long as 14 days after apheresis, with the degree of change related to the volume of the apheresis procedure. NIH platelet donors had significantly higher bone density measurements than control subjects in the study and reference populations provided by the instrument manufacturer. A less marked positive effect on bone density was observed in NIH leukpaheresis donors, while no benefit was observed in community donors. These effects for increased bone density in NIH apheresis donors are consistent with anabolic effects of parathyroid hormone when released in a pulsatile rather than a tonic fashion, and may be related to increased levels of osteoprotegerin found in NIH platelet donors. Osteoprotegerin synthesis may be induced by repeated apheresis donations performed on an every 4 week cycle; the molecule blocks the activation of osteoclast cells which can induce bone breakdown. The degree of this effect is likely to be impacted by the frequency and intensity (flow rate) of apheresis procedures. Studies are continuing to evaluate the impact of prophylactic intravenous calcium supplementation during apheresis on bone density markers. 1. Ronquillo JR, Alvandi F, Reynolds JC, Cecco SA, Wesley RA, Yau YY, Oblitas JM, Collins MT, Rehak NN, Leitman SF, Bolan CD. Citrate effects and bone mineral density (BMD) in serial long-term apheresis odnors. Transfusion 45:15A, 2005.