Plasmapheresis

Plasmapheresis (from the Greek plasma, something molded, and apheresis, taking away) is the removal, treatment, and return of (components of) blood plasma from blood circulation. It is thus an extracorporeal therapy. The method can also be used to collect plasma for further manufacturing into a variety of medications.

As Therapy
During plasmapheresis, blood is initially taken out of the body through a needle or previously implanted catheter. Plasma is then removed from the blood by a cell separator. Three procedures are commonly used to separate the plasma from the blood:


 * Discontinuous flow centrifugation : One venous catheter line is required. Typically, a 300 ml batch of blood is removed at a time and centrifuged to separate plasma from blood cells.


 * Continuous flow centrifugation : Two venous lines are used. This method requires slightly less blood volume to be out of the body at any one time as it is able to continuously spin out plasma.


 * Plasma filtration : Two venous lines are used. The plasma is filtered using standard hemodialysis equipment. This continuous process requires less than 100 ml of blood to be outside the body at one time.

Each method has its advantages and disadvantages. After plasma separation, the blood cells are returned to the person undergoing treatment, while the plasma, which contains the antibodies, is first treated and then returned to the patient in traditional plasmapheresis. (In plasma exchange, the removed plasma is discarded and the patient receives replacement donor plasma or saline with added proteins.) Medication to keep the blood from clotting (an anticoagulant) is generally given to the patient during the procedure. Plasmapheresis is used as a therapy in particular diseases. It is an uncommon treatment in the United States, but it is more popular in Europe and particularly Japan.

An important use of plasmapheresis is in the therapy of autoimmune disorders, where the rapid removal of disease-causing autoantibodies from the circulation is required in addition to slower medical therapy. It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, where simultaneous medical and imunosuppressive therapy is required for long term management. Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be stopped, usually by the use of medications that suppress the immune system, such as prednisone, cyclophosphamide, cyclosporine, mycophenilate mofetil, and/or rituximab.

Other uses are the removal of blood proteins where these are overly abundant and cause hyperviscosity syndrome.

Examples of diseases that can be treated with plasmapheresis:
 * Guillain-Barré syndrome
 * Chronic inflammatory demyelinating polyneuropathy
 * Goodpasture's syndrome
 * Hyperviscosity syndromes:
 * Cryoglobulinemia
 * Paraproteinemia
 * Waldenström macroglobulinemia
 * Myasthenia gravis
 * Thrombotic thrombocytopenic purpura (TTP)/Hemolytic Uremic Syndrome
 * Wegener's granulomatosis
 * Lambert-Eaton Syndrome
 * Antiphospholipid-Antibody Syndrome (APL)
 * Wegner's Granulomatosis
 * Microscopic Polyangiitis
 * Recurrent Focal & Segmental Glomerulosclerosis in the transplanted kidney

Complications of Plasmapharesis Therapy
Though plasmapharesis is helpful in certain medical conditions, like any other therapy, there are potential risks and complications. Insertion of a rather large intravenous catheter can lead to bleeding, lung puncture (depending on the site of catheter insertion), and, if the catheter is left in too long, it can get infected.

Aside from placing the catheter, the procedure itself has complications. When blood is outside of the body, while it is passing through the plasmapharesis filter, blood has a tendency to clot. To reduce this tendency, citrate is infused while the blood is running through the circuit. Citrate binds to calcium in the blood; calcium is essential for blood to clot. While citrate is very effective in preventing blood from clotting; however, its use can lead to life-threatening low calcium levels. To prevent this complication, calcium is infused intravenously while the patient is undergoing the plasmapharesis; in addition, calcium supplementation by mouth may also be given.

A second common complication of the plasmapharesis procedure is the potential exposure to blood products

A third complication is suppression of the patient's immune system

A fourth complication is bleeding.

As Manufacturing Process
Plasma donation is in many ways similar to whole-blood donation, though the end product is used for different purposes. Almost all plasmapheresis in the US is performed by automated apheresis machines.


 * Manual Method : For the manual method, approximately the same as a blood donation is collected from the donor. The collected blood is then centrifuged, the plasma is pressed out of the collection set into a satellite container, and the red blood cells are returned to the donor.  Since the plasma is replaced rapidly by the body, a donor can provide up to a liter of plasma at a time and can donate with only a few days between donations, unlike the 56 day deferral for whole blood donation.  The amount allowed in a donation varies vastly from country to country, but generally does not exceed two donations, each as much as a liter, per 7-day period.

The theoretic danger with this method was that if the wrong red blood cells are returned to the wrong donor, a serious and potentially fatal transfusion reaction would occur, although requiring donors to recite their names and ID numbers on returned bags of red cells eliminated this risk.


 * Automated Method : The automated method uses almost exactly the same process except that the collection, separation, and return are all performed inside a machine which is connected to the donor and there is no risk of receiving the wrong red cells. The devices used are very similar to the devices used for therapeutic plasmapheresis.

In either case, if a significant amount of red blood cells cannot be returned the donor may not donate for 56 days, just as if they had donated a unit of blood.

The collected plasma is promptly frozen at -20 degrees C and is typically shipped to a processing facility for fractionation. This process separates the collected plasma into specific components, such as albumin and immunoglobulins, most of which are made into medications for human use. Sometimes the plasma is thawed and transfused as Fresh Frozen Plasma (FFP), much like the plasma from a normal blood donation.

Donors are sometimes immunized against agents such as Tetanus or Hepatitis B so that their plasma contains the antibodies against the toxin or disease. The collected plasma then contains these components, which are used in treating the diseases in question. Donors who are already ill may have their plasma collected for use as a positive control for laboratory testing.

Plasma donors are typically paid cash for their donations. Since the products are heavily processed and treated to remove infectious agents, the higher risk is considered acceptable. Standards for plasma donation are set by national regulatory agencies such as the FDA and by a professional organization, the Plasma Protein Therapeutics Association or PPTA, which audits and accredits collection facilities. The National Donor Deferral Registry (NDDR) is also maintained by the PPTA for use in keeping incurably infected persons from donating. In former times, however, the plasmapheresis industry was accused of lax donor requirements and practices, i.e., facilities in rundown neighborhoods and entire cities already having large numbers of disease infected persons.