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Apheresis -- therapeutic

A. Physician coverage.

In general, you do not have to be present on campus while a therapeutic apheresis is being done. We tell the clinical physician that if a problem occurs, the apheresis team will contact them, as they have the best overall knowledge of the patient's condition and medications. A clinical physician must be available on campus and be able to respond within minutes during a therapeutic apheresis if a problem occurs. If they say this is not possible, do not proceed with the apheresis until suitable coverage is arranged. Consult with blood bank faculty if necessary.

B. Indications.

You must approve any new request for a therapeutic apheresis procedure. Suggested indications are given in Appendix 9 in the paper supplement. We do not follow these absolutely; they are only a guide. It is most important to use your common sense: What will we be accomplishing by doing a therapeutic apheresis? Is the benefit worth the risk of doing an invasive procedure? Contact blood bank faculty or fellow if you are not sure. Do not assume that the requesting physician necessarily knows more about this procedure than you do, especially if they are a first or second year resident. We are the experts in apheresis. I guarantee you than no other residents get formal training in apheresis like you have had. Therefore, if the request does not make sense to you, do not blindly OK it.

C. Emergency procedures.

Apheresis procedures should be scheduled for weekdays between 8:00am and 5:00pm whenever possible. However, if you are called after hours or on the weekend, you must decide if it is appropriate to call in the apheresis team to do the first procedure immediately. You will have to use your clinical judgement in this regard. Leukocyte reductions for acute leukemia, or platelet reductions for thrombocythemia are generally emergencies, as are treatment of transplant rejection or saving of kidney function in lupus or glomerulonephritis. Goodpasture's disease is usually an emergency. Red cell exchange because of priapism or acute chest syndrome is usually an emergency. If the clinical team can't seem to decide if it's an emergency or not, then the procedure can probably wait until the next day. Similarly, if the patient has waited around all day to have the catheter placed for intravenous access, and the catheter placement is not completed until late evening, the procedure can likely wait until early the next morning. The apheresis team would generally prefer to come in at 6 am to start than to come in at 11 pm because then they can get at least some sleep. If you decide to contact the apheresis team, call 590-8211 to find out who is on call.

D. Paperwork.

If you believe a therapeutic apheresis is indicated, fill out a consultation form. There should be copies in your call manual. Use the proper form for the hospital where the patient is being seen. Give this paperwork to the daytime blood bank resident or fellow/faculty the next working day. It must be signed by an attending prior to distribution to the chart.

E. Replacement fluids.

The replacement fluid of choice for plasmapheresis will almost always be 5% albumin or plasma protein fraction (PPF). PPF is a 5% solution (isotonic) that is very similar to albumin, but may be available in larger quantities. Do not approve the use of fresh frozen plasma as a replacement fluid unless one of the following situations exists:

  1. ABO-incompatible liver transplant. These patients are rejecting their liver grafts and therefore are not making clotting factors.
  2. Thrombotic thrombocytopenic purpura (TTP)
  3. Systemic coagulopathy coincident with disease to be treated (for example, patient with severe liver disease and prolonged PT/aPTT).

Some procedures will not need colloid replacement, although these are the exception. For example, a patient undergoing plasmapheresis for hyperviscosity may need very little if any colloid replacement. They certainly don't need 100% colloid replacement per plasma volume removed. You may be able to replace them with 2/3 saline and 1/3 PPF. Consult with the apheresis supervisor and blood bank faculty for help. Selective apheresis procedures do not need colloid fluid replacement. Such procedures include treatment of hypercholesterolemia with the LDL adsorption filter and the removal of IgG and immune complexes via the staphylococcal protein A column (Prosorba). In both of these procedures, most of the patient's own plasma is returned to their body; only selective substances are removed.

Leukoreduction and platelet-reduction phereses use very little, if any, colloid replacement. Relatively little of the patient's plasma is removed and discarded.

F. Use of Red Blood Cells.

Of course RBCs are used as the replacement fluid in red cell exhange pheresis procedures. Packed RBCs are just fine for this purpose, although whole blood could be used if that's all that's available. The apheresis team prefers packed RBCs. It makes no difference to the patient because the apheresis instrument will adjust whatever concentration of incoming fluids you use to end up with the desired final hematocrit in the patient. RBCs are also needed to prime the extracorporeal tubing in small children and infants needing an apheresis procedure when > or = 15% of their blood volume will be in the extracorporeal circuit. The apheresis team will tell you when this is needed for a particular patient based on the size of the child.

Crossmatching must be performed for the RBCs used in apheresis, just like for regular transfusion. The clinical team must draw a specimen for type and crossmatch and send it to the laboratory well in advance of the procedure. The clinical physician must also specify in his/her orders in the chart that RBCs are to be used.

G. Length of procedure/size of exchange.

Many times the requesting physician is well experienced in ordering apheresis procedures and knows what size plasma volume processing he/she desires. However, if the physician is not used to ordering plasmaphereses, they may need our input. Do not demand that they must make the decision! If they have no strong preference, or they just have no idea, it's up to you to decide. I suggest starting a new procedure at 1 1/2 plasma volumes replaced. This is a reasonable size -- it would remove about 75% of an intravascular substance, yet can usually be accomplished within a couple of hours. If the substance you need to remove is IgG (so that it equilibrates with other body compartments) and the patient needs quick results, you might go to a 2 volume exchange. It will take longer, but should remove more of the desired substance. I would not suggest doing a procedure larger than two volumes at one sitting. For a fairly small return in improved removal, you end up spending disproportionately more time doing the procedure. This is stressful not only for the apheresis team, but for the patient as well. If the clinician is insisting on a larger volume exchange procedure, please get blood bank faculty or fellow involved.

On the other hand, if the patient is particularly unstable, or has been tolerating procedures poorly, you might go with only a one plasma volume exchange.

The actual length of the procedure will depend not only on the amount of plasma processed, but the size of the patient and the speed at which the blood can be processed through the machine, which is dependent on the type of access and the cardiovascular stability of the patient.

H. Complications.

The most common complications during therapeutic apheresis are those that relate to the patient's underlying condition. The patients being treated by this procedure are often very ill. Other possible complications to consider are those related to volume shifts and extracorporeal circulation (for example, hypotension). Citrate toxicity is a possibility, but is very unusual in our experience, occurring only in patients undergoing procedures of 4 hours in length. If the question of citrate toxicity arises, have the nurses draw an ionized calcium level and suggest calcium replacement if it is low. The clinical team will make the actual decision whether or not calcium is needed. Coagulopathies resulting from the apheresis procedure are also very rare, although the PT/PTT may be prolonged immediately after the procedure if checked. It is not clear that mild prolongations right after pheresis have any clinical significance.

Anaphylactic like reactions characterized by flushing, hypotension, dyspnea and bradycardia have been reported in patients undergoing therapeutic plasma exchange, LDL apheresis and affinity column apheresis while receiving angiotension-converting enzyme (ACE) inhibitor therapy. It is recommended that ACE inhibitors be withheld for at least 24 hours before a procedure. See Appendix 10 in the paper call manual supplement for a list of ACE inhibitors.

Contaminated blood products or incompatible blood are possible complications if FFP or RBCs are used. Allergy symptoms are not uncommon and can be severe and life-threatening. Be aware that anaphylaxis to transfused FFP is seen on our service one or two times a year, and allergy to PPF or albumin is also possible. Further apheresis procedures should be delayed until the etiology of severe reactions is fully explored.

A transfusion reaction during apheresis should be worked up just like the infusion of blood components without pheresis. The apheresis team should instigate the work-up and fill out the report of reaction, draw the specimens and send them to the lab. The clinical physician should be notified of the reaction. Further blood should not be given until incompatibility is ruled out.

I. Physician's orders and informed consent.

The clinical physician must write an order on the patient's chart authorizing our team to perform apheresis. This order must be present prior to the start of the procedure. The physician may simply write: "Therapeutic plasmapheresis, one and one-half volumes, with plasma protein fraction replacement daily for three days" or something similar. The clinical physician is also responsible for obtaining special consent for the apheresis procedure itself and for the use of blood if RBCs or FFP are to be used during the pheresis. If the clinical physician is unable to obtain consent, the on call pathology resident may perform this function.

J. Venous access.

An 11.5 french Quinton catheter is ideal, however, other thick walled, double lumen catheters, which can accommodate high flow rates, are acceptable. Acceptable catheters should be placed by radiology special procedures (590-8503) if the catheter is needed during regular hours. (Be sure to make it clear to the individual placing the catheter that it will be used for apheresis). We can perform 1-2 procedures using peripheral veins in some patients, especially if the procedure is needed emergently. These patients will need to be compliant (i.e. able to be still for several hours) and evaluated by the apheresis team for suitable peripheral veins. If emergent after hours placement of the catheter is absolutely necessary the catheter can be placed by either the renal or surgery services. In these situations the apheresis team can provide a Quinton catheter if necessary.

Peripheral veins may be used for therapeutic apheresis, but it is rare that a patient has suitable veins that can be re-stuck daily for several consecutive procedures. Additionally, the patient is usually uncomfortable because they cannot move either arm for 2 to 3 hours at a time.

K. Location for apheresis.

Therapeutic apheresis procedures must be performed on campus in the hospital or clinic. If the patient is an inpatient, we will perform the procedure in his/her room. If the patient is an outpatient, we will need to find space to do the procedure. This may involve a room in a clinic (e.g., Hematology-Oncology clinic) or the Apheresis Clinic room (room 861 located on 8 west). We have occasionally done a procedure in the emergency room while a patient was waiting to be admitted, but this is not optimal.

Occasionally you will be contacted about performing a therapeutic apheresis procedure at a different (unaffiliated) hospital, e.g. Doctor's Hospital, or Mesquite Community. We are not able to help with these at this time. We have no way to transport equipment, and we are not covered by liability insurance to work at other hospitals. If necessary, the patient needing treatment can be transferred to the care of a physician who has admitting privileges at one of our hospitals and who is willing to take on the clinical care of the patient. We can then treat the patient at our own facility.

L. Number of procedures.

There is generally no magic number of procedures that should be performed for a given patient. In many cases, the patient is reevaluated after 2 or 3 procedures to see if they are responding. For many diseases, such as the neurologic syndromes, the clinicians have set formulas that they follow. This is fine, as long as it seems reasonable. For example, they may do 5 procedures over two weeks. Other times, the procedure is done daily until the patient improves (Examples: TTP and ABO-incompatible liver transplant rejection. Improvement in the patient with TTP is followed by monitoring the platelet count and the LDH level. The liver transplant patient has serial antibody titers followed -- see page 44). Some procedures are one time only -- for example, leukoreduction and red cell exchange are done one time in most patients. Only rarely is a second leukoreduction needed, although the WBC values may not drop as much as desired after one procedure. You may need to remind the clinician that the extent of drop in WBC count cannot be predicted after apheresis. If the patient is producing a lot of WBCs, the count may not drop much and may even rise after pheresis. Don't let this surprise you -- the apheresis team can save the discard bag and count the number of WBCs removed if the clinicians give you a hard time about not doing the procedure right.

M. Peripheral blood stem cell collection.

Generally this procedure will not be performed after hours or on weekends, and if it is done on a weekend, the arrangements should already have been made with the daytime residents. This is a planned, elective procedure, not an emergency. BloodCare picks up the cells for freezing and storage after our team performs the apheresis using the Cobe Spectra. BloodCare is responsible for sending small samples from the collection bag for quality control testing, specifically mononuclear cell counts, bacterial and fungal cultures, and CD34 assays.

N. Specific immunoadsorption procedures (use of columns).

  1. LDL-cholesterol specific apheresis. This procedure is now FDA approved for hypercholesterolemia in patients not responding to standard diet and therapeutic regimens. Off-label use has included treatment of severe hypertriglyceridemia with pancreatitis. Only 3 physicians on campus are approved to order this procedure: Dr. Dan Stein, Dr. Sue Williams and Dr. Kenny Jialal. Refer orders from any other physicians to the fellow or faculty. If contacted about emergency treatment of a new patient with severely high cholesterol (e.g. >600) you could suggest regular plasmapheresis.
  2. Selective immunoadsorption of IgG/immune complexes by Imré Prosorba column. This system uses a staphylococcal protein A column to remove immune complexes containing IgG from the circulation. It is FDA approved only for thrombocytopenia patients: specifically, ITP, HIV-associated thrombocytopenia, and patients refractory to platelet transfusion. We have reserved use of this system for patients refractory to more conventional methods of treatment. The columns must be ordered from Seattle; none are stocked routinely. They cost approximately $800 each (in addition to the cost of pheresis) and a series of six procedures is recommended as one course of therapy.
  3. Anti-A and anti-B removal by immunoadsorption. A company called Chembiomed in Canada makes immunoadsorption columns for anti-A or anti-B. These columns are not FDA-approved. We have, however, used them in the past under an emergency compassionate use waiver for an ABO-incompatible liver transplant who was doing very poorly. We do not have any of these devices on campus. Please contact faculty with any requests for this procedure. We currently perform regular plasma exchange to remove anti-A or anti-B in liver transplant rejection.

O. Photopheresis.

We no longer perform this procedure.

P. Manual therapeutic apheresis.

The need for a manual apheresis procedure with current resources for automated procedures should be exceedingly rare. I would discourage any requests for manual apheresis unless it makes sense to do the procedure without the automated equipment. In most cases automatic apheresis is preferred because of ease of operation, decreased time required, decreased risk of bacterial contamination, and decreased risk of giving the patient back the wrong blood.

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