Transfusion Medicine - Jeffrey McCullough

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little impact on in vivo anticoagulation. Bleeding due to citrate anticoagulation is not a problem for donors.

      Citrate toxicity

      Elevations of blood citrate can cause paresthesias, muscle cramping, tetany, cardiac arrhythmia, and other symptoms. The plateletpheresis procedure involves the administration of citrate solutions to donors, resulting from the massive autologous retransfusion of 4–6 L of their blood may be withdrawn, passed through the instrument, citrated, and returned to them during the procedure. In a careful study relating the dose of citrate, symptoms, electrocardiographic changes, and ionized calcium [84] showed that when citrate infusion rates were maintained at less than 65 mg/kg/hour, donors did not experience symptoms or demonstrate electrocardiographic abnormalities. This has been confirmed in later studies [85, 86]. Donors with similar levels of hypocalcemia may demonstrate wide variability in symptoms. Using anticoagulant citrate dextrose formula A at a ratio of 1:8 with whole blood, many abnormalities were observed, including bradycardia (sometimes severe); supraventricular and ventricular premature contractions; right bundle‐branch block; ST segment elevation or depression; and tall, flattened, or inverted T waves. Some of the donors experienced nausea, vomiting, hypotension, fainting, or convulsions [87]. Even when less citrate is infused, the QT interval is almost always prolonged [88, 89]. Citrate reactions are managed by slowing the flow rate of the instrument and thus slowing the rate of citrate infusion. This is quite effective in eliminating these reactions, and most apheresis personnel are very aware of this process. Oral or intravenous calcium can also be used to reverse or prevent this condition. Citrate toxicity can also occur inadvertently if tubing is not properly placed in the pumps and the citrate solution is allowed to flow freely into the donor [90].

      Circulatory effects

      Because the extracorporeal volume of the cytapheresis instruments is small (usually less than 200 mL), hypovolemia is rare and these donors do not experience circulatory problems. This becomes a more significant consideration in small donors (e.g., children) or donors with very low hemoglobin levels, populations who could be undergoing therapeutic procedures.

      Air embolus

      Because the blood is actively pumped into the donor’s veins, there is the theoretical possibility that air could be pumped into the donor if air enters the system. Some of the early models of apheresis instruments contained bubble chambers connected to a device that stopped the pumps if the chamber became filled with air. Air emboli have occurred but without reports of serious consequences. Contemporary instruments do not contain safety devices to prevent air embolus, and so this complication remains a concern. Staff members must be aware of this possibility and ensure that containers and tubing sets do not develop leaks that would allow air to enter the system.

      Hematoma

      Mechanical hemolysis

      Because blood is pumped through tubing and centrifuges of various configurations, hemolysis is a theoretical complication due to constricted tubing or the geometry of the flow pathways. When this rare event occurs in practice, generally a defective collection kit is suspected [91, 92].

      Platelet depletion or damage

      Plateletpheresis does not damage the donor’s remaining platelets, and the donor’s platelet function is normal after donation [93]. Removal of platelets equivalent to several units of the donor’s blood does not result in thrombocytopenia. In a rather dramatic example, a female donor underwent 101 donations during a 33‐month period, with donation frequencies ranging from once to three times weekly [94]. Her platelet count remained in the range of 135,000–430,000 during this time. In donors who undergo repeated plateletpheresis, the platelet count decreases somewhat more, but then stabilizes [78, 95]. Thus, it appears that platelets can be donated safely approximately every 2–4 days if needed.

      Lymphocyte depletion

      Instruments and procedures have been improved to minimize the leukocyte content in the product, and thus also avoid potential complications of lymphocyte depletion in the donor. As a result, most plateletpheresis procedures today remove about 1 × 106 to 5 × 107 leukocytes. Loss of this number of leukocytes is very unlikely to lead to leukocyte depletion or any clinical effects on the donor’s immune function and has the advantage of producing a leukodepleted product. This is true even after serial collections completed in a relatively short period [96, 97]. However, in studies using the previously employed methods, significant lymphocyte depletion was observed together with decrease in total lymphocyte count and B and T cells, lower T4/T8 ratio, and reduced mitogen response [98–100]. Separate studies indicated that at least 109 lymphocytes must be removed daily to observe a significant decline in lymphocyte count and at least 1011 lymphocytes total must be removed over a short time and/or the individual’s lymphocyte count must be less than 500/μL for clinical immunosuppression to occur [97, 101]. The most recent studies show that although there is variability in lymphocyte loss in serial donors with the two most common collection instruments, the loss does not appear to lead to any clinical predisposition to infection [102–104]. Although one study suggests a possible increased risk of immunosuppression related infections [105].

      Complications unique to granulocyte donation

      The complications related to leukapheresis itself are not different from those in plateletpheresis, but donors receive HES, corticosteroids, and possibly G‐CSF that can cause additional problems. Although there are only a few studies of side effects in frequent granulocyte donors [106], experience with stem cell donors has also provided information about side effects [107]. Short‐term effects of HES include rashes and fluid shifts, while the effects of corticosteroids and G‐CSF are also well known and are discussed in Chapter 6. Although there have been concerns about long‐term effects, such as cataracts [108, 109] or malignancy [110], in repeat donors, these have not been confirmed in studies.

      Complications unique to plasmapheresis

      One unexpected risk from plasmapheresis, especially when done frequently for therapeutic purposes, is the development of anemia, which is probably due to the blood samples used for laboratory testing [111].

      Complications unique to mononuclear cell apheresis for collection of peripheral blood stem cells

      Because of the low level of circulating PBSCs in normal donors, donors receive the hematopoietic growth factor G‐CSF to mobilize PBSCs and increase the yield. G‐CSF is also often used, sometimes in combination with glucocorticoids, to increase yields for granulocyte collections. G‐CSF, itself, is associated with a high frequency of side effects and is responsible for most of the complications of the donation of mononuclear cells as a source of PBSCs [107].

      1 1. Fung MK, Eder AF, Spitalnik S, Westhoff CM, eds. Technical Manual, 19th edn. Arlington, VA: American Association of Blood Banks, 2017.

      2 2. Custer B, Johnson ES, Sullivan SD, et al. Quantifying losses to the donated blood supply due to donor deferral

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