Citrate Effects and Bone Density in Long-Term Apheresis Donors
Condition: Healthy Apheresis Donors
Study type: Observational

Summary: 
      This study will examine the effects of repeated apheresis procedures on bone density and
      calcium balance. Apheresis is a procedure for collecting large numbers of a specific blood
      component, such as white cells (leukapheresis) or platelets (plateletpheresis). For the
      procedure, whole blood is collected through a needle in an arm vein and is directed through a
      machine that separates it into its components by spinning. The desired cells are removed and
      the rest of the blood is returned to the donor, either through the same needle or through a
      needle in the other arm. A blood thinning medicine called citrate is added to the
      cell-separating machine. Citrate reduces the ionized calcium levels in the blood, which
      prevents the blood from clotting. When the blood is returned to the donor, the donor also
      receives the citrate. This lowers the donor's ionized calcium levels which may irritate nerve
      and muscle cells, causing tingling around the mouth, hands, and feet during the procedure.
      The reduced ionized calcium levels result in increased parathyroid hormone levels in the
      donor, can effect bone calcium stores. In addition, some of the citrate that is returned to
      the donor is excreted in the urine along with calcium, which causes further loss of calcium
      from the body. It is not known if the calcium loss during apheresis in people who undergo
      this procedure repeatedly has any long-term effects on body calcium balance and bone calcium
      stores. This study will measure bone density and calcium balance in long-term platelet and
      white cell donors and compare the findings with those of whole blood donors, who do not
      receive citrate.

      Healthy people between 18 and 80 years of age who weigh between 110 and 300 pounds, do not
      have a metal prosthesis, and are not pregnant may be eligible for this study. Participants
      undergo the following procedures:

      Whole blood donors

        -  Blood sample collection 2 weeks before blood donation.

        -  I removed undergo standard whole blood donation

        -  Urine sample collection.

        -  DEXA scan to assess bone density by measuring bone calcium stores. For this procedure,
           the subject lies still on a table while the spine, hip, and whole body are scanned using
           a small amount of radiation. The forearm is also scanned while the subject is seated.
           The scan may be repeated after 2 years.

      Plateletpheresis and leukapheresis donors

        -  Standard platelet or white cell donation.

        -  Blood sample collections immediately prior to and after donation, and on the first,
           fourth, and fourteenth days after donation.

        -  Urine sample collections at the beginning and at the end of the apheresis procedure and
           on the first, fourth, and fourteenth days after the donation.

        -  DEXA scan at the beginning of the study (no earlier than 2 weeks after their latest
           apheresis donation). The scan may be repeated after 2 years.

        -  Some apheresis donors may be asked to have a second procedure in which they take calcium
           according to standard guidelines for plateletpheresis and leukapheresis. During the
           second procedure, platelet donors will take oral calcium tablets before starting
           plateletpheresis. White cell donors will receive calcium intravenously (through a vein)
           during the second leukapheresis. For this second procedure, the donors provide
           additional blood and urine samples as described above.
    

Detailed description: 
      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 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.1-3
      Adverse effects related to citrate administration are common; the most well-studied is acute
      hypocalcemia due to the formation of calcium-citrate complexes. Recent studies in our
      Department indicate that changes in serum calcium, PTH, osteocalcin, alkaline phosphatase,
      and vitamin D levels are also present and may be sustained for up to 24 hours after
      apheresis. Observations from European studies suggest that serial plateletpheresis donation
      may be associated with reduced bone density; however, those studies did not include a control
      group, and involved paid donors, who generally were generally younger, allowed to donate more
      frequently, and not representative of the population demographics of the U.S. In addition to
      volunteer plateletpheresis donors, the NIH Department of Transfusion Medicine maintains a
      registry of approximately 500 persons who undergo leukapheresis procedures to provide
      components for in vitro research use, for which they receive compensation. These research
      apheresis procedures use the same devices as plateletpheresis donations, and also require
      citrate anticoagulant infusions. However, the procedure duration and total dose of citrate
      administered 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. The impact of serial, frequent, long-term
      apheresis donations on total body calcium balance and bone density are unknown. In this
      study, we will measure bone density and laboratory tests in 75 NIH plateletpheresis donors,
      75 NIH research leukapheresis donors, and in a control group of 150 age, gender, and race
      matched NIH whole blood donors. The apheresis study groups will each include at least 50
      frequent donors (greater than 50 donations during the past 10 years) and 20 donors with less
      than 25 lifetime donations. Comprehensive laboratory evaluations of the effect of citrate
      administration on bone metabolism and body calcium and magnesium metabolism before and after
      apheresis will be performed. Similar laboratory and bone density measurements will be
      performed in 75 subjects who donate platelets at facilities outside of NIH (non-NIH donors),
      and who undergo plateletpheresis at more frequent intervals than NIH donors. The effect of
      intravenous calcium administration on apheresis-induced changes in these laboratory
      parameters will also be assessed. This information will have a major impact on our
      understanding of the short and long-term adverse effects of citrate administration in
      committed apheresis donors, and may also provide insight into calcium, magnesium, and
      phosphorus metabolism.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Existing NIH donors@@@@@@
      
Keywords: Hypocalcemia; Plateletpheresis; Calcium; Citrate; Bone Density; Natural History; Healthy Volunteer; HV