Therapeutic Membrane Plasmapheresis
Plasmapheresis is a term used to describe multiple forms of extracorporeal plasma separation. Plasma is the fluid portion of the blood, and it carries proteins and other substances around the body. Plasmapheresis is able to separate blood cells from plasma, and therein lies the potential for its therapeutic use. A wide variety of autoimmune disorders are caused by antibodies that mistakenly target a patient's cells, causing the body to attack itself.
These "self-targeting" antibodies can be effectively removed during treatment with plasmapheresis; in the case of membrane plasmapheresis (discussed in detail further down on this page), there are pores in the membrane so small that the blood cells cannot pass through BUT the plasma containing the aberrant antibodies CAN. Plasmapheresis is mostly used to treat autoimmune diseases, but can also be used as a therapy for other diseases in which abnormal types or quantities of other substances (proteins, cholesterol, etc.) are circulating in the plasma.
The two main types are centrifugation and membrane filtration. The centrifugation technique involves using a centrifuge to separate the blood plasma and cellular components. This technique for plasmapheresis has been around since the 1930's (in animal experimentation) and since the 1960's as a therapeutic application in humans. Plasma filtration through a membrane was introduced in the late 1970's for use in therapeutic plasmapheresis. Plasma filtration through a membrane has the advantage of having much less blood outside of the body at any point in time.
Membrane plasmapheresis machines work in much the same way as hemodialysis machines. Blood is generally passed through a number of membranes; usually one but possibly two in more selective applications. Secondary plasma filtration allows for a more selective elimination of dangerous macromolecules while allowing important plasma components to be recombined with plasma. The primary membrane is used to separate the cellular and plasma components. The secondary filter is then used to separate the plasma component into two solutions, one which is discarded, and another which is recombined.
A general overview of plasmapheresis
How is plasmapheresis performed on patients?
Plasmapheresis can either be done on an outpatient or inpatient basis. This procedure generally takes a few hours; the number of treatments a patient needs varies greatly based upon their specific diagnosis. A patient can be reclining in a chair or lying down on a bed while undergoing this procedure. In this relaxed position a catheter is inserted into a large vein, usually in the arm. At the same time, another catheter is inserted into the opposite arm (or sometimes the opposite foot). The blood is taken from the patient, passed though a membrane, after which the separated blood cells are combined with replacement fluids and returned to the patient. Although this procedure can be quite uncomfortable, it is ordinarily not painful. Anticoagulants are used in conjunction with plasmapheresis to prevent the formation of blood clots, which can occasionally lead to excessive bleeding. Patients can receive plasmapheresis at most major medical centers and clinics across the country.
What does a plasmapheresis apparatus do to your blood?
In membrane plasmapheresis, blood is pumped through a plasma filter which consists of a membrane and ultra filtration solution. The plasma filter separates blood into a plasma component and cellular component. The cellular component is reinserted into the blood stream along with plasma components that are selectively re-added to the cellular component.
The system above is a double filter membrane plasmapheresis machine. A simpler system can created by eliminating the second filter. In this system blood is first filtered into the cellular and plasma components, then the plasma components are further seperated into the wanted and unwanted proteins. Part of the plasma is discarded and the rest is recombined with the cellular component and supplemental fluid and reinserted into the patient.
The different solutes in the blood are filtered across the membrane using a variety of factors. The membranes are generally highly permeable to small molecules and selectively permeable to larger molecules. Part of the filitration is accomplished by simple diffusion. The smallest molecules are highly permeable at the membrane interface and easily move across the membrane to equalize concentrations.
Filtration is also partially achieved by ultrafiltration. By controlling the fluid pressure on both sides of the membrane, fluid H20 can be induced to move across pressure gradients. The pressure gradient along with a membrane that is selectively permeable to essential macromolecules such as red blood cells allowing for the separation of the initial blood into its two components.
Plasmapheresis systems can be designed to use either pumps or gravity to assist the pressure supplied by the circulatory system (blood pressure). A plasmapheresis system that relies only on gravity and blood pressure and eliminates the usage of pumps in the circuit was first described by Lysaght et al. in 1983 and is known as "spontaneous membrane plasmapheresis."
How are Exchange Volumes determined?
Kinetic modeling considerations inform us that exchange of one blood volume offers 64% reduction in concentrations while 1.5 times the plasma volume offers 78% reduction in concentration. Any additional increase in blood volume has no useful affect on blood concentrations.
How is a plasmapheresis apparatus designed to limit hemolysis?
Hemolysis is influence by a number of factors including applied operating pressure, cell diameter, cell membrane tension, the membrane pore diameter, and the cell-pore resistence time. The critical hemolytic pressure for a device therefore will vary along with the membrane. When choosing a membrane therefore one must not only select one that filters the correct macromolecules, a membrane has to be chosen which will adequately limit the tension faced by red blood cells to limit hemolysis. To limit hemolysis the driving pressure across the membrane, pore size, and cell-pore resistence time have to be calibrated such that cell membrane tension is kept below critical values
What types of membranes are used?
There are many different membranes that are available for therapeutic use.
| cellulose diacetate (hollow fiber) | Plasmaflo-AP05H (Asahi Medical, Tokyo, Japan) | ||
| Plasmaflo-AP05 (Asahi Medical) | |||
| polypropylene (hollow fiber) | Fenwal CPS-10 (Baxter, Deerfield, IL, USA) | ||
| Hemaplex-BT900 (Dideco, Mirrandola, MO, USA) | |||
| Curesis M82 (Organon Teknika, Durham, NC, USA) | |||
| polypropylene (flat plate) | Centry TPE (Cobe, Lakewood, CO, USA) | ||
| polysulfone (hollow fiber) | Sulflux-FS (Kaneka, New York, NY, USA) | ||
| polymethylmethacrylate (hollow fiber) | Plasmax-PS05 (Toray, Tokyo, Japan) |
Sources:
Nose Y, Malchesky, PS. Therapeutic Membrane Plasmapheresis. Therapeutic Apheresis 2000; 4.Siami G, Siami F. Membrane Plasmapheresis in the United States: A Review Over the Last 20 Years. Therapeutic Apheresis 2001; 5.
Image Sources:
http://www.iconocast.com/NewsS1_Files/A7SA7/News6_clip_image004.gifhttp://www.iconocast.com/NewsS1_Files/A7SA7/News6_clip_image004.gif
http://www.blackwell-synergy.com/doi/pdf/10.1046/j.1526-0968.2002.00428.x
http://www.indiana.edu/~phys215/lecture/lecnotes/lecgraphics/diffusion2.gif
http://www.armfield.co.uk/images/ft18_solutes.jpg
http://www.blackwell-synergy.com/doi/pdf/10.1046/j.1526-0968.2000.00231.x
Bio 1080 (Organ Replacement) - Spring 2008
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