apheresis

Whole blood enters the centrifuge on the left and separates into layers so that selected components can be drawn off on the right.

Apheresis (Greek: "to take away") is a medical technology in which the blood of a donor or patient is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation. It is thus an extracorporeal therapy.

Method

Depending on the substance that is being removed, different processes are employed in apheresis. If separation by weight is required, centrifugation is the most common method. Other methods involve absorption onto beads coated with an absorbent material and filtration.

The centrifugation method can be divided into two basic categories:

Continuous flow centrifugation (CFC)

Continuous flow centrifugation (CFC) historically required two venipunctures as the "continuous" means the blood is collected, spun, and returned simultaneously. Newer systems can use a single venipuncture. The main advantage of this system is the low extracorporeal volume (calculated by volume of the apheresis chamber, the donor's hematocrit, and total blood volume of the donor) used in the procedure, which may be advantageous in the elderly and for children.

Intermittent flow centrifugation

Intermittent flow centrifugation works in cycles, taking blood, spinning/processing it and then giving back the unnecessary parts to the donor in a bolus. The main advantage is a single venipuncture site. To stop the blood from coagulating, anticoagulant is automatically mixed with the blood as it is pumped from the body into the apheresis machine.

Centrifugation Variables

The centrifugation process itself has four variables that can be controlled to selectively remove desired components. The first is spin speed and bowl diameter, the second is "sit time" in centrifuge, the third is solutes added, and the fourth is not as easily controllable: plasma volume and cellular content of the donor. The end product in most cases is the classic sedimented blood sample with the RBC's at the bottom, the "buffy coat" of platelets and WBC's (lymphocytes/granulocytes (PMN's, basophils, eosinophils/monocytes) in the middle and the plasma on top.

Types of apheresis

Disinfect, insert the cannula, pull out the cannula, dress the wound. The blue pressure cuff is controlled by the platelet apheresis machine in newer models.

There are numerous types of apheresis.

Donation

Blood taken from a healthy donor can be separated into its component parts during blood donation, where the needed component is collected and the "unused" components are returned to the donor. Fluid replacement is usually not needed in these type of collections. There are large categories of component collections:

• Plasmapheresis - blood plasma. Plasmapheresis is useful in collecting FFP (fresh frozen plasma) of a particular ABO group. Commercial uses aside from FFP for this procedure include immune globulin products, plasma derivatives, and collection of rare WBC and RBC antibodies.
• Plateletpheresis (thrombapheresis, thrombocytapheresis) - blood platelets. Plateletpheresis, like it sounds, is the collection of platelets by apheresis; while returning the RBC's, WBC's, and component plasma. The yield is normally the equivalent of between six and ten random platelet concentrates. Quality control demands the platelets from apheresis be equal to or greater than 3.0 x 10^11 in number and have a pH of equal to or greater than 6.2 in 90% of the products tested and must be used within five days.
• Leukapheresis - leukocytes (white blood cells). Leukopheresis is the removal of PMN's, basophils, eosinophils for transfusion into patients whose PMN's are ineffective or traditional therapy has failed. There is limited data to suggest the benefit of granulocyte infusion. The complications of this procedure are the difficulty in collection and short shelf life (24 hours at 20 to 24 C). Since the "buffy coat" layer sits directly atop the RBC layer, HES, a sedimenting agent, is employed to improve yield while minimizing RBC collection. Quality control demands the resultant concentrate be 1.0 x 10^10 granulocytes in 75% of the units tested and that the product be irradiated to avoid graft-versus-host disease (inactivate lymphocytes). Irradiation does not affect PMN function. Since there is usually a small amount of RBC's collected, ABO compatibility should be employed when feasible.
• Stem cell harvesting - circulating bone marrow cells are harvested to use in bone marrow transplantation.

Donor Safety

• Single use kits - Apheresis is done using single-use kits, so there is no risk of infection from blood-contaminated tubing or centrifuge.
• Immune system effects - "the immediate decreases in blood lymphocyte counts and serum immunoglobulin concentrations are of slight to moderate degree and are without known adverse effects. Less information is available regarding long-term alterations of the immune system" ^[1]

Kit Problems

• Baxter recall - "Pinhole leaks were observed at the two-omega end of the umbilicus (multilumen tubing), causing a blood leak. "^[2]
• Fenwal recall - "Fenwal has become aware of two instances where the anticoagulant citrate dextrose (ACD) and saline lines were reversed in the assembly process. The reversed line connections may not be visually apparent in the monitor box, and could result in excessive ACD infusion and severe injury, including death, to the donor. Fenwal will contact its customers to arrange for product return." ^[3]

Plasticizer exposure

Apheresis uses plastics and tubing, which come into contact with the blood. The plastics are made of PVC in addition to additives such as a plasticizer, often DEHP. DEHP leaches from the plastic into the blood, and people have begun to study the possible effects of this leached DEHP on donors (as well as, obviously, transfusion recipients).

• ""current risk or preventive limit values for DEHP such as the RfD of the US EPA (20 μg/kg/day) and the TDI of the European Union (20-48 μg/kg/day) can be exceeded on the day of the plate-letpheresis. . . . Especially women in their reproductive age need to be protected from DEHP exposures exceeding the above mentioned preventive limit values." ^[4]
• "Commercial plateletpheresis disposables release considerable amounts of DEHP during the apheresis procedure, but the total dose of DEHP retained by the donor is within the normal range of DEHP exposure of the general population." ^[5]
• The Baxter company manufactured blood bags without DEHP, but there was little demand for the product in the marketplace ^[6]
• Some apheresis products are now manufactured in China. ^[7]
• "Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 μg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed." ^[8]

Therapy

The assembly (A-D), operation (E) and disassembly (F) of the platelet apheresis machine which can be configured to separate other components as well.

The various apheresis techniques may be used whenever the removed constituent is causing severe symptoms of disease. Generally, apheresis has to be performed fairly often, and is an invasive process. It is therefore only employed if other means to control a particular disease have failed, or the symptoms are of such a nature that waiting for medication to become effective would cause suffering or risk of complications.

• LDL apheresis - removal of low density lipoprotein in patients with familial hypercholesterolemia.
• Photopheresis
• Immunoadsorbtion with Staphylococcal protein A-agarose column - removal of allo- and autoantibodies (in autoimmune diseases, transplant rejection, hemophilia) by directing plasma through protein A-agarose columns. Protein A is a cell wall component produced by several strains of Staphylococcus aureus which binds to the Fc region of IgG.

Donation and Therapy

• Erythrocytapheresis- red blood cells. Erythrocytapheresis is the separation of erythrocytes from whole blood. It is most commonly accomplished using the method of centrifugal sedimentation. This process is used for red blood cell diseases such as sickle cell crises or severe malaria. The automated red blood cell collection procedure for donating erythrocytes is referred to as 'Double Reds' or 'Double Red Cell Apheresis.'^[9]

Fluid replacement during apheresis

It is important to remember that when the apheresis system is used for therapy the system is removing relatively small amounts of fluid (not more than 10.5 mL/kg body weight). That fluid must be replaced to keep correct intravascular volume. The fluid replaced is different at different institutions. If a crystalloid like normal saline is used, the infusion amount should be triple what is removed as the three to one ratio of NS for plasma is needed to keep up oncotic pressure. Some institutions use normal serum albumin, but it is costly and can be difficult to find. Some advocate using FFP or a similar blood product, but there are dangers including citrate toxicity (from the anticoagulant), ABO incompatibility, infection, and cellular antigens.

Intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a blood product administered intravenously. It contains the pooled IgG immunoglobulins (antibodies extracted from the plasma of thousands of blood donors). IVIG is given as a protein replacement therapy for immune deficient patients which have decreased or abolished antibody production capabilities. IVIG is administered to maintain adequate antibodies levels to prevent infections and confers a passive immunity. IVIG effects last between 2 weeks and 3 months. It is mainly used as treatment in three major categories:

• Immune deficiencies, such as X-linked agammaglobulinemia, hypogammaglobulinemia (primary immune deficiencies), and acquired compromised immunity conditions (secondary immune deficiencies), featuring low antibody levels;
• Inflammatory and autoimmune diseases
• Acute infections

See also

• Leukoreduction
• Venipuncture

References

1. ^ http://www3.interscience.wiley.com/journal/113467388/abstract
2. ^ http://www.fda.gov/CbER/recalls/baxaphe013105.htm "Recall of Amicus Apheresis Kits, Baxter Healthcare Corporation" , US FDA, Jan 31 2005
3. ^ http://www.fda.gov/CbER/recalls/aphfen062107.htm "Recall of CS3000 Apheresis Kits", US Food and Drug Administration, June 21, 2007
4. ^ http://cat.inist.fr/?aModele=afficheN&cpsidt=17299235 Archives of toxicology ISSN 0340-5761 CODEN ARTODN 2005, vol. 79, no12, pp. 689-693 [5 page(s) (article)] (1 p.1/4)
5. ^ http://www.ingentaconnect.com/content/bsc/trf/2003/00000043/00000008/art00019 " Donor exposure to the plasticizer di(2-ethylhexyl)phthalate during plateletpheresis" , Source: Transfusion, Volume 43, Number 8, August 2003 , pp. 1115-1120(6)
6. ^ http://www.highbeam.com/doc/1G1-56958320.html "SO FAR, PHTHALATE ALTERNATIVES HAVEN'T INSPIRED MUCH DEMAND.", Article from: Plastics News ,October 25, 1999 , Toloken, Steve
7. ^ http://nigale.en.alibaba.com/offerdetail/203354126/Sell_Single_use_Apheresis_Plasma_Separating_Kit.html
8. ^ http://cat.inist.fr/?aModele=afficheN&cpsidt=17286818 International journal of hygiene and environmental health ISSN 1438-4639 , 2005, vol. 208, no6, pp. 489-498 [10 page(s) (article)] (2 p.) "Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors"
9. ^ dtm double red cell

R. Bambauer, R. Latza, M.R. Lentz (2009): Therapeutic Plasma Exchange and Selective Plasma Separation Methods – Fundamental Technologies, Pathology and Clinical Results. Pabst, Lengerich/Berlin, 428 Seiten, ISBN 978-3-89967-458-3

External links

• [1]
• Apheresis News
• American Society for Apheresis
• WebPath Apheresis page.
• WebPath Blood Donation and Processing
• Donating Platelet Apheresis: Facts and the FAQ
• Baxter: Automated Component Collection
• Haemonetics: PCS2 System
• Haemonetics: MCS+ 9000 Dystem
• CaridianBCT: Trima Automated Blood Collection System