Apheresis

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Apheresis
Apheresis.svg
Whole blood enters the centrifuge (1) and separates into plasma (2), leukocytes (3), and erythrocytes (4). Selected components are then drawn off (5).
MeSHD016238

Apheresis (ἀφαίρεσις (aphairesis, "a taking away")) is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation. It is thus an extracorporeal therapy.

The apheresis machine was invented by American medical technologist Herb Cullis in 1972.[1]

One of the uses of apheresis is for collecting stem cells.[2]

Method[edit]

Depending on the substance that is being removed, different processes are employed in apheresis. If separation by density 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[edit]

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[edit]

Intermittent flow centrifugation works in cycles, taking blood, spinning/processing it and then giving back the unused 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[edit]

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[edit]

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[edit]

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 this type of collection. There are large categories of component collections:

  • Plasmapheresisblood plasma. Plasmapheresis is useful in collecting FFP (fresh frozen plasma) of a particular ABO group. Commercial uses aside from FFP for this procedure include immunoglobulin products, plasma derivatives, and collection of rare WBC and RBC antibodies.
  • Erythrocytapheresisred 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.'[3]
  • Plateletpheresis (thrombapheresis, thrombocytapheresis) – blood platelets. Plateletpheresis is the collection of platelets by apheresis while returning the RBCs, WBCs, 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 × 1011 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.
  • Leukapheresisleukocytes (white blood cells). Leukopheresis is the removal of PMNs, basophils, eosinophils for transfusion into patients whose PMNs are ineffective or where traditional therapy has failed. There is limited data to suggest the benefit of granulocyte transfusion. 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 × 1010 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 RBCs 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[edit]

  • 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"[4]
Kit problems[edit]

Two apheresis kit recalls were:

  • Baxter Healthcare Corporation (2005), in which "pinhole leaks were observed at the two-omega end of the umbilicus (multilumen tubing), causing a blood leak."[5]
  • Fenwal Incorporated (2007), in which there were "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."[6]
Plasticizer exposure[edit]

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 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 plateletpheresis. . . . Especially women in their reproductive age need to be protected from DEHP exposures exceeding the above mentioned preventive limit values."[7]
  • "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."[8]
  • The Baxter company manufactured blood bags without DEHP, but there was little demand for the product in the marketplace[9]
  • "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."[10]

Therapy[edit]

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.

Indications[edit]

ASFA categories[edit]

In 2010, the American Society for Apheresis published the 5th Special Edition(1)[11] of evidence based guidelines for the practice of Apheresis Medicine. These guidelines are based upon a systematic review of available scientific literature. Clinical utility for a given disease is denoted by assignment of an ASFA Category (I – IV). The quality and strength of evidence are denoted by standard GRADE recommendations. ASFA Categories are defined as follows:

  • Category I for disorders where therapeutic apheresis is accepted as a first line treatment,
  • Category II for disorders where therapeutic apheresis is accepted as a second-line treatment,
  • Category III for disorders where the optimal role of therapeutic apheresis is not clearly established and
  • Category IV for disorders where therapeutic apheresis is considered ineffective or harmful.

Diseases and disorders[edit]

Disease[notes 1] Special condition[12] Type of apheresis[12] ASFA
category[12]
ABO-incompatible hematopoietic stem cell transplantation Plasmapheresis II
ABO-incompatible solid organ transplantation Kidney Plasmapheresis II
Heart (<40 months of age) II
Liver (perioperative) III
Acute disseminated encephalomyelitis Plasmapheresis II
Acute inflammatory demyelinating polyneuropathy Plasmapheresis I
Acute liver failure Plasmapheresis III
Age-related macular degeneration (AMD) Dry AMD Rheopheresis III
Systemic amyloidosis Plasmapheresis IV
Amyotrophic lateral sclerosis Plasmapheresis IV
Anti-neutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis Dialysis dependence Plasmapheresis I
Diffuse alveolar pulmonary hemorrhage (DAH) I
Dialysis independence III
Goodpasture syndrome Dialysis independence Plasmapheresis I
Diffuse alveolar hemorrhage (DAH) I
Dialysis dependence and no DAH III
Aplastic anemia or pure red cell aplasia Aplastic anemia Plasmapheresis III
Pure red cell aplasia II
Autoimmune hemolytic anemia Warm antibody autoimmune hemolytic anemia Plasmapheresis III
Cold agglutinin disease, life-threatening II
Babesiosis Severe Erythrocytapheresis I
High-risk population II
Burn with circulatory shock Plasmapheresis IV
Heart transplant with allograft Prophylaxis of rejection Photopheresis I
Treatment of rejection II
Treatment of antibody-mediated rejection Plasmapheresis I
Catastrophic antiphospholipid syndrome Plasmapheresis I
Rasmussen's encephalitis Plasmapheresis or immunoadsorption II
Chronic inflammatory demyelinating polyneuropathy Plasmapheresis I
Coagulation factor inhibitors Immunoadsorption III
Plasmapheresis IV
Cryoglobulinemia Severe/symptomatic Plasmapheresis I
Secondary to Hepatitis C Immunoadsorption II
Cutaneous T cell lymphoma: mycosis fungoides or Sézary disease Erythrodermic Photopheresis I
Non-erythrodermic III
Dermatomyositis or polymyositis Plasmapheresis IV
Leukapheresis IV
Dilated cardiomyopathy NYHA class II-IV Immunoadsorption or plasmapheresis III
Familial hypercholesterolemia Homozygotes LDL apheresis I
Heterozygotes II
Homozygotes with small blood volume Plasmapheresis II
Focal segmental glomerulosclerosis Recurrent Plasmapheresis I
Graft-versus-host disease Skin Plasmapheresis II
Non-skin III
Hemolytic disease of the fetus Before intrauterine transfusion availability Plasmapheresis II
Hereditary hemochromatosis Erythrocytapheresis III
Hemolytic uremic syndrome (HUS) Atypical HUS due to mutations in complement factor genes Plasmapheresis II
Atypical HUS due to factor H autoantibodies I
Typical HUS, or diarrhea-associated HUS IV
Leukocytosis Leukostasis Leukapheresis I
Prophylaxis of leukostasis III
Hyperviscosity in monoclonal gammopathy Treatment of symptoms Plasmapheresis I
Prophylaxis in rituximab
Immune thrombocytopenic purpura Plasmapheresis IV
Immune complex-type of rapidly progressive glomerulonephritis Plasmapheresis III
Inclusion body myositis Plasmapheresis or leukapheresis IV
Inflammatory bowel disease Leukapheresis II
Kidney transplantation Antibody-mediated rejection Plasmapheresis I
Desensitization (medicine) in living donor in positive crossmatch due to donor specific HLA antibody II
High PRA and cadaveric donor III
Lambert-Eaton myasthenic syndrome Plasmapheresis II
Lung transplantation Allograft rejection Plasmapheresis II
Malaria Severe Erythrocytapheresis II
Multiple sclerosis Acute CNS IDD unresponsive to steroids Plasmapheresis II
Chronic progressive III
Myasthenia gravis Moderate to severe Plasmapheresis I
Pre-thymectomy I
Myeloma cast nephropathy Plasmapheresis II
Nephrogenic systemic fibrosis Photopheresis or Plasmapheresis III
Neuromyelitis optica Plasmapheresis II
Venoms, poisoning and overdose Mushroom poisoning Plasmapheresis II
Other III
Paraneoplastic syndrome Neurologic Plasmapheresis or immunoadsorption III
Pancreatitis Secondary to hypertriglyceridemia Plasmapheresis III
Polyneuropathy due to monoclonal gammopathy IgG, IgA or IgM Plasmapheresis I
Multiple myeloma III
IgG/IgA or IgM Immunoadsorption III
PANDAS and Sydenham's chorea Plasmapheresis I
Pemphigus vulgaris Plasmapheresis IV
Photopheresis III
Refsum disease Plasmapheresis II
Polycythemia vera or erythrocytosis Erythrocytapheresis III
POEMS syndrome Plasmapheresis IV
Post-transfusion purpura Plasmapheresis III
Psoriasis Plasmapheresis IV
Rheumatoid arthritis Refractory Immunoadsorption II
Schizophrenia Plasmapheresis IV
Systemic scleroderma Plasmapheresis III
Photopheresis IV
Sepsis with multiorgan failure Plasmapheresis III
Sickle cell disease Acute stroke Erythrocytapheresis I
Acute chest syndrome II
Prophylaxis of stroke or transfusional iron overload II
Multi-organ failure III
Stiff-person syndrome Plasmapheresis IV
Systemic lupus erythematosus Severe, such as cerebritis or diffuse alveolar hemorrhage Plasmapheresis II
Nephritis IV
Thrombocytosis Symptomatic Plateletpheresis II
Prophylactic III
Thrombotic microangiopathy, drug-associated Plasmapheresis I
III
IV
Thrombotic microangiopathy, hematopoietic stem cell transplantation-related Plasmapheresis III
Thrombotic thrombocytopenic purpura Plasmapheresis I
Thyroid storm Plasmapheresis III
Wilson’s disease Fulminant hepatic failure with hemolysis Plasmapheresis I

Fluid replacement during apheresis[edit]

When an 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 (NS) is used, the infusion amount should be triple what is removed as the 3:1 ratio of normal saline 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 fresh frozen plasma (FFP) or a similar blood product, but there are dangers including citrate toxicity (from the anticoagulant), ABO incompatibility, infection, and cellular antigens.

See also[edit]

Notes[edit]

  1. ^ Only diseases (or mentioned special conditions thereof) with ASFA category I or II are given in bold.

References[edit]

  1. ^ "Did you know? 10 Historical Facts about Blood Transfusion". Retrieved 2019-01-23.
  2. ^ Katherine, Abel (2013). Official CPC Certification Study Guide. American Medical Association. p. 128.
  3. ^ dtm double red cell Archived July 5, 2007, at the Wayback Machine
  4. ^ Strauss, Ronald G. (1984). "Apheresis donor safety – changes in humoral and cellular immunity". Journal of Clinical Apheresis. 2 (1): 68–80. doi:10.1002/jca.2920020112. PMID 6536660.
  5. ^ "Archived copy". Archived from the original on 2009-01-17. Retrieved 2008-12-20.CS1 maint: archived copy as title (link) "Recall of Amicus Apheresis Kits, Baxter Healthcare Corporation", US FDA, Jan 31 2005
  6. ^ "Recall of CS3000 Apheresis Kits", US Food and Drug Administration, June 21, 2007
  7. ^ Koch, Holger M.; Bolt, Hermann M.; Preuss, Ralf; Eckstein, Reinhold; Weisbach, Volker; Angerer, Jürgen (2005). "Intravenous exposure to di(2-ethylhexyl)phthalate (DEHP): Metabolites of DEHP in urine after a voluntary platelet donation". Archives of Toxicology. 79 (12): 689–93. doi:10.1007/s00204-005-0004-x. PMID 16059725.
  8. ^ Buchta, Christoph; Bittner, Claudia; Höcker, Paul; Macher, Maria; Schmid, Rainer; Seger, Christoph; Dettke, Markus (2003). "Donor exposure to the plasticizer di(2-ethylhexyl)phthalate during plateletpheresis". Transfusion. 43 (8): 1115–20. doi:10.1046/j.1537-2995.2003.00479.x. PMID 12869118. S2CID 34539126.
  9. ^ "SO FAR, PHTHALATE ALTERNATIVES HAVEN'T INSPIRED MUCH DEMAND"[dead link], Plastics News, October 25, 1999, Toloken, Steve
  10. ^ Koch, Holger M.; Angerer, Jürgen; Drexler, Hans; Eckstein, Reinhold; Weisbach, Volker (2005). "Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors". International Journal of Hygiene and Environmental Health. 208 (6): 489–98. doi:10.1016/j.ijheh.2005.07.001. PMID 16325559.
  11. ^ Szczepiorkowski, Zbigniew M.; Winters, Jeffrey L.; Bandarenko, Nicholas; Kim, Haewon C.; Linenberger, Michael L.; Marques, Marisa B.; Sarode, Ravindra; Schwartz, Joseph; et al. (2010). "Guidelines on the use of therapeutic apheresis in clinical practice-Evidence-based approach from the apheresis applications committee of the American Society for Apheresis" (PDF). Journal of Clinical Apheresis. 25 (3): 83–177. doi:10.1002/jca.20240. PMID 20568098.
  12. ^ a b c Unless otherwise specified in boxes, reference is: Szczepiorkowski, Zbigniew M.; Winters, Jeffrey L.; Bandarenko, Nicholas; Kim, Haewon C.; Linenberger, Michael L.; Marques, Marisa B.; Sarode, Ravindra; Schwartz, Joseph; Weinstein, Robert; Shaz, Beth H. (2010). "Guidelines on the use of therapeutic apheresis in clinical practice-Evidence-based approach from the apheresis applications committee of the American Society for Apheresis" (PDF). Journal of Clinical Apheresis. 25 (3): 83–177. doi:10.1002/jca.20240. ISSN 0733-2459. PMID 20568098.

External links[edit]