Citrate Effects and Bone Mineral Density (BMD) in Serial Long-Term Apheresis Donors.
Authors: Bolan Charles , Ronquillo Jeremiah , Yau Yu Ying , Wesley Robert , Cecco Stacey , Alvandi Firoozeh , Reynolds James , Byrne Phyllis , Matthews Cynthia , Cantilena Cathy , Collins Michael , Rehak Nadja , Leitman Susan 
Published: October 2019

-Background: Citrate-induced changes in biochemical markers of calcium balance and bone metabolism have been described for at least 24 hours after plateletpheresis. However, the long-term effect of frequent apheresis on BMD and calcium balance has not been determined.

Methods: Volunteer platelet donors (PD) and financially-compensated lymphocyte donors (LD), each with > 50 donations over 10 yrs, were compared with volunteer whole blood (WB) donor controls. All subjects underwent BMD testing by dual energy x-ray absorptiometry (Delphi Advanced Instrument, Hologic, MA). Laboratory evaluations were performed at baseline, and immediately and at 1, 4, and 14 days after apheresis. The minimum interapheresis donation period established by institutional policy was 4 wks in PD, and 3 weeks in LD, thus additional BMD assessments were performed in community platelet donors (APD), each with > 100 donations over 10 yrs, conducted at a minimum interapheresis interval of 2 weeks.

Results: Seventy–six PD, 53 LD, 118 WB, and 21 APD donors were evaluated. PD were older (57 vs 50 yo), weighed less (80 vs 88 kg), and were more likely to be female (41% vs 26%) and Caucasian (99 vs 64%) than LD. WB had intermediate demographic values (53 yo, 85 kg, 40% female, 77% Caucasian). APD had similar age (58 yo), wt (88 kg), and race (100% Caucasian) but were 95% male and had a mean of 206 lifetime donations versus 88 for PD and 80 for LD. Compared to PD, LD underwent larger procedures (7 vs 5 liters) at lower citrate infusion rates (1.3 vs 1.6 mg/kg/min). PD also exhibited attenuated post-apheresis changes in ionized Ca (iCa, 0.97 vs 0.93 mmole/L) and intact PTH (iPTH, 87 vs 106 pg/mL), and had more marked post-apheresis changes in markers of bone breakdown (c-telopeptides; 73 vs 43% increase) and bone remodeling (osteocalcin, 50 vs 25% increase). LD, but not PD, had persistent 10 to 20% increases in iPTH levels on days 1, 4, and 14 after apheresis, while both LD and PD demonstrated smaller, but statistically significant increases in iCa, total Ca, and phosphorus on day 14 after apheresis. PD had higher mean BMD than the gender, race, and age adjusted reference standards at all sites tested, and had higher BMD values at the femoral neck, hip and radius than WB controls matched for race, gender, menopausal status, age (± 5 yrs) and weight (± 10 kg). A similar, but less pronounced pattern was observed in LD, with mean BMD values significantly higher than reference values or matched WB controls only at the femoral neck. The frequency of osteopenia (36, 15, and 49%) and osteoporosis (4, 8 and 13%) in PD, LD and WB donors, respectively, tended to be lower in the frequent apheresis donors. BMD in APD donors did not differ significantly from WB controls and was significantly lower than PD at the femoral neck and hip.

Conclusion: Apheresis induces citrate-mediated biochemical effects consistent with an acute period of bone resorption followed by a more gradual period of recovery. Repetitive, frequent plateletpheresis in PD subjects was associated with positive effects on bone density, as has been described with the use of PTH as a pharmacologic therapy for low BMD in other clinical settings. The net effects on calcium balance, bone metabolism, and BMD may be further impacted by alterations in the frequency and intensity of citrate administration.