Artificial Organs Vol. 5 , No. 3

Establishing a Therapeutic Pheresis Program

Jeanne A. Cona

i i

ABSTRACT Pheresis techniques have been used to collect large quantities of specific blood components from single donors for many years. These techniques have been modified to methods for therapy in certain disease processes. The adaption of pheresis to a type of therapy requires that many factors be taken into consideration and the following describes these factors.

Key words: therapeutic pheresis, anticoagulation, replacement fluids, vascular access

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INTRODUCTION Pheresis has been demonstrated to be a successful mo- dality of treatment in a variety of disease states. Clin- ical investigations of new applications for pheresis are still under development. New pheresis programs are being established to meet the demand for therapeutic pheresis treatment.

a therapeutic pheresis program. Following is a discussion of some requirements for

Physical Facility The location of the pheresis procedure may be in a

treatment room or at the patient’s bedside. To perform pheresis on patients not admitted to the hospital, a room should be selected which is well ventilated, has good lighting, and can maintain a minimum tem- perature of 68°F. Figure I illustrates a typical layout of a treatment room.

Electrical outlets must be available to provide an isolated circuit for each pheresis instrument. Addi- tional outlets are required to handle other equipment which will be located in the treatment room.

Equipment and Supplies In Addition to Pheresis Instrument These items and supplies should be located in the treat- ment room:

A. patient bed or donor chair B. telephone and/or intercom system C. sink and counter space

D. E. F. G. H.

I.

J. K. L. M. N.

Address for correspondence: Haemoneties SA. Chemin du Reposoir 3-5, CH-1260, Nyon, Switzerland.

Received: November 1980

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Fig. 1 Physical Layout of Pheresis Unit

large trash container with liner blood pressure cuff (aneroid) stethoscope thermometer emergency medical supplies 1. drugs 2. oxygen 3. airwaylpadded tongue depressor 4. electrocardiogram machine 5. defibrillator small centrifuge (combination centrifuge for tubes and microcrit tubes) 1. alcohol wipes 2. 2 x 2 gauze sponges 3. lancets 4. microcrit tubes 5. hematocrit reader 6. red top tubes tube clamps or rubber-shodded hemostats scissors/tube stripperltube sealer and clips emesis basin blankets disposable supplies for venipuncture 1. antiseptic soap 2. antiseptic solution 3. tape 4. sterile gauze pads

0160-564XI81/229-233/$2.50 Copyright 0 1981 International Society for Artificial Organs

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August 1981 Therapeutic Pheresis Prograin

5. adhesive strips 6. disposable gloves 7. Chux padsitowels

0. hand gripper P. sterile disposable supply storage

1. pheresis packs 2. venipuncture needles 3. Y-type recipient sets 4. transfer packs

1. 0.9% normal saline 2. replacement fluids 3. anticoagulants test tubes and rack for various pre- and post-treatment laboratory determinations clock with a second hand

Q. solutions

R.

S. T. dietary scale (gram) U. calculator

Laboratory Determinations Prior to each procedure, a hematocrit must be

taken for the calculations necessary to select the proper disposable bowl. The patient’s hematocrit is used to determine the maximum removal of plasma per pass which restricts the extracorporeal volume to less than 15%.l

The patient undergoing a course of plasma (exchange) pheresis procedures must be scheduled for periodic protein electropheresis determinations.2 A de- termination of total serum protein can be accomplished with the plasma from the microhematocrit tube and a refractometer.

The frequency and types of other laboratory deter- minations are dependent upon the individual patient’s diagnosis and treatment regimen.

Personnel In the pheresis of normal healthy donors, the oper-

ators’ backgrounds and qualifications vary greatly. Pheresis operators selected for a therapeutic pheresis program are most often Registered Nurses due to their experience in patient care.

The individuals chosen to work in a therapeutic pheresis program must be mature, -stable, self-reliant, and should have a strong medical-surgical background. Nurses filling these requirements may be found in the intensive care unit, hemodialysis unit, emergency room and operating room. These nurses usually have the skills required to deal with volume management and emergency situations.

Pheresis operators are trained at the facility where they will be working. Training is usually supplied by the company from which the instrument is purchased.

Medical Considerations Many thousands of pheresis procedures are done

safely each month. Most procedures involve healthy volunteer donors for the collection of platelets and/or white cells for supportive therapy.

When a patient is to be pheresed, special care must be exercised over and above the care provided for nor- mal, healthy donors.

The following are guidelines for the patient’s evaluation: Patient history

The physician should review the patient’s past and current medical history and write orders specific for the patient’s therapeutic pheresis as indicated by his phys- ical status.

The pheresis operator must also review the pa- tient’s history and should interview the patient prior to each procedure to determine if the patient’s status has changed since the last treatment.

A minimum physical examination consisting of vi- tal signs and hematocrit should be completed prior to initiation of each pheresis procedure.

Vascular access Good vascular access is essential t o the per-

formance of a pheresis procedure. The most common access is through one or two peripheral veins. Fre- quently a large, firm antecubital vein is chosen for the draw site. In a two-arm procedure, an antecubital vein of the other arm, or a more distal forearm vein, is se- lected for reinfusion.

A 16-gauge needle or short catheter is inserted in the selected vessel after the skin area over the vessel has been properly prepared. Since resistance to flow varies directly with the length of the needle or catheter, the shortest practical needle or catheter should be selected.

Some patients may have external shunts, internal fistulas, grafts or indwelling catheters to facilitate vas- cular access. The pheresis operator must understand the differences between these access routes and should have supervision if the operator is inexperienced.

External shunts are surgically implanted cannu- lae, usually with Teflon tips attached to a silicone body. The tubes exit the body through two skin wounds. When the shunt is not being used for hemodialysis or pheresis, the two ends are joined together by a Teflon connector permitting blood flow from artery to vein. A common location for an external shunt is the in- ner surface of the forearm, about two inches above the wrist.3

Some problems associated with external shunts are:

1. The requirement that the patient wear a

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Artificial Organs Vol. 5 , No. 3

dressing to avoid damage to or separation of the shunt.

2. The danger of shunt separation and heavy blood loss from the arterial side.

3. Clotting of the shunt. 4. Subcutaneous shun t tubing erosion

through the skin. 5. Infection at the exit of the shunt through

the skin. Proper techniques of shunt care must be under-

stood by the pheresis operators. They should instruct the patient in the proper home care of the shunt.

Internal arteriovenous fistulas are a frequently used route for hemodialysis and may also be used for pheresis.

An internal fistula is created surgically by making an incision in an adjacent artery and vein and anas- tomosing the vessels together. The opening causes a diversion of the high pressure arterial blood into the vein, making the vein dilate. This allows for easy in- sertion of large gauge needles. The internal fistula does not restrict the patient in carrying out his normal daily routine.

Other means are available to create internal vas- cular access, for example:

1. Bovine grafts (bovine vessels treated with a gluteraldehyde process) may be used soon after insertion. In the surgical pro- cedure, one end of the graft is attached to an artery; the other to a vein.

2. Synthetic grafts may be implanted in a technique similar to that for bovine grafts, but must remain in place a longer period of time prior to use.

3. A saphenous vein may be surgically re- moved from the patient's leg and tunneled subcutaneously in the forearm. One end is attached to an artery and the other to a vein. After healing, the transplanted vein will become prominent and can be used for vascular access. T h o surgical sites are re- quired for this procedure.

Anticoagulation The pheresis patient is not usually given systemic

anticoagulation. Instead his blood is regionally anti- coagulated as it enters the extracorporeal circuit. Both citrate solutions and heparin are used as anti- coagulants. Each drug has characteristics which must be considered in making the selection for a particular patient.

Citrate anticoagulant is available as a trisodium citrate concentrate which must be diluted to achieve the concentration required. Citrate may also be ob- tained in premixed solutions as anticoagulant citrate

dextrose (ACD) formula A or B. The A solution has approximately 50% greater concentration of citrate than the B solution. The dextrose in these solutions is provided for survival of cells collected from a normal donor. It is not required for a therapeutic procedure.

Citrate anticoagulants work by binding with calci- um, a necessary element in the coagulation process. Infusion of citrate decreases the free calcium levels of the patient4 and can cause a number of symptoms such as circumoral paraesthesias, metallic taste in mouth, nasal congestion, and nausea. If citrate continues to be administered to the patient after these initial symp- toms, reactions may progress as far as tetany, con- vulsions, cardiac arrythmia, and cardiac arrest.

Symptoms of citrate reaction are most commonly treated by reducing the infusion rate of the citrated blood and/or the administration of calcium gluconate. Calcium gluconate is administered by slow intra- venous injection through a peripheral line cleared of any citrated blood or blood products.

Special precautions must be taken with unreliable or unresponsive patients who may not report early symptoms of citrate toxicity. Patients, especially in this group, should be considered for continuous cardiac monitoring during the pheresis procedure.

Heparin is sometimes used as an anticoagulant in plasma exchange. Heparin inhibits the clotting of blood and the formation of fibrin clots both in vitro and vivo. In combination with a cofactor, heparin inactivates thrombin and thus prevents the conversion of fibrino- gen to fibrin.5

The use of heparin in pheresis causes some system- ic anticoagulation due to the return of blood which has been heparinized in the extracorporeal circuit. In plas- ma exchange, this is not of great concern since most of the heparin added to the blood is discarded in the plas- ma. Neutralization of the heparin with protamine is rarely needed due to the small amount received during the procedure.

Heparin is derived from animal tissue and has been known to cause allergic reactions. Any patient with known animal allergies should be considered for a trial does of 1,000 Units prior to the pr~cedure.~

Replacement Fluids Replacement fluids are required when the ther-

apeutic pheresis procedure involves removal of large volumes of plasma.

Protocols for fluid replacement are as varied as are the diseases being treated with plasma exchange.621 Since an optimum protocol for replacement has not been established, the physician should consider the po- tential effect of each fluid prior to making a selection for the patient.

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August 1981 Therapeutic Pheresis Program

Crystalloids and colloids have been used alone and in combination in many procedures. Crystalloids are safe and effective fluids to replace volume, but their administration causes a change in oncotic pressure. This change may result in a fluid shift from the intra- vascular to interstitial space.” If this shift occurs, the circulating volume will decrease and a greater replace- ment volume than the volume removed will be required to maintain normal circulating volume.

The additional volume of crystalloid solution will cause a weight gain and could be an additional burden on a patient with compromised cardiac function.

If the replacement crystalloid is to be mixed with the patient’s citrated red cells, normal saline is the solution of choice?’ Other crystalloid solutions contain electrolytes which, when mixed with citrated blood, re- place the citrate-bound calcium. This would allow the coagulation process to progress with potential for mi- croemboli formation or clotting.”

If electrolyte solutions are chosen as the replace- ment fluid, they should be given through a separate line or “piggybacked” into the reinfusion line. If “piggybacked”, the electrolyte solution should be run only after all the red cells have been infused and the line rinsed thoroughly with normal saline.

Colloid solutions maintain adequate oncotic pres- sures but have other characteristics which must be considered.

Normal serum albumin (human) 5% and plasma protein fraction (human) 5% have an oncotic effect equal to normal plasma. These solutions are prepared from large pools of adult human plasma which have been pasteurized and are free from the risk of hepatitis transmission. The use of 200 ml of either of these solu- tions gives the osmotic effect of one unit of plasma.23

It is important to note that plasma protein fraction administration has been reported to cause hypotension. The patient should be observed and monitored for this possible effect.”

Normal serum albumin (human) 25% is a more concentrated product. Administration of the 25% con- centrate will cause an increase in the plasma oncotic pressure drawing fluid away from the interstitial into the intravascular c~rnpartment.’~ This can cause intra- vascular volume overload.

Some clinicians choose to dilute the 25% solution in normal saline to a 5% solution. The addition of 200 ml of 25% albumin to 800 ml normal saline yields 1000 ml of replacement fluid at a 5% concentration of albumin.

When large volumes of plasma are exchanged, electrolyte levels may be depressed. Electrolyte levels should be monitored and corrected t o avoid con- sequences such as low arterial pressure or cardiac ar- rythmia related to low potassium levels.

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Fresh frozen plasma may be used and is relatively inexpensive. It has all the qualities of the removed plasma including clotting factors. Replacement of clott- ing factors may be required in patients with abnormal clotting parameters, however, this exposes the patient to multiple donors and increases the risk of hepatitis transmission.

Replacement fluids are rarely needed in the ther- apeutic pheresis procedure to remove platelets, lym- phocytes, or granulocytes. The volume removed is usu- ally less than 300 ml. The amount of normal saline used in priming and the anticoagulant added to the blood usually approximate the removed volume.24

References 1. 2.

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5. 6.

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10.

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13.

14.

15.

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Technical Manual, American Association of Blood Banks. Committee on Standards American Association of Blood Banks, Standards for Blood Banks and %ansfusion Services, Ninth Edition, 1978. GUTCH, CF, MARTHA H STONER. Review of Hemodialysis for Nurses and Dialysis Personnel. CV Mosby, 1979, Chapter 9. LANDERSON, JH, WV MILLER, LA SHERMAN. Relationship of Physical Symptoms, ECG, Free Calcium, and Other Blood Chemistries in Reinfusion with Citrated Blood. Transfusion, Nov.-Dec. 1978, Vol. 18, No. 6, p. 670. Physicians Desk Reference, 30th Edition, 1976, p. 943. BRANDA, R. Plasma Exchange in the ‘IZeatment of Immune Thrombocytopenia. Proceedings of the Haemonetics Research Institute Advanced Component Seminar, Boston, MA, 1978. COBCROFT, R, G TAMAGNIMI and KM DORMANDY. Serial Plas- mapheresis in a Haemophiliac with Antibodies to Factor VIII. Proceedings of the Haemonetics Research Institute Advanced Component Seminar, London, England, 1977. GILCHER, RONALD 0. Plasma Exchange in Immune and Auto- immune Diseases. Proceedings of the Haemonetics Research Institute Advanced Component Seminar, Boston, MA, 1978. GOLDMAN, J O H N A, HELEN L CASEY, et al. Limited Plas- mapheresis in Rheumatoid Arthritis with Vasculitis. Brief Reports, p. 1146. HOWARD, JAMES F, DONALD B SANDERS and TR JOHNS. The Role of Plasma Exchange Therapy in Myasthenia Gravis. Pro- ceedings of the Haemonetics Research Institute Advanced Com- ponent Seminar, Boston, MA, 1978. JONES, J VERRIER, RH CUMMING, RC BUCKNALL, et al. A Ther- apeutic Role for Plasmapheresis in the Management of Acute Systemic Lupus Erythematosus. Proceedings of the Hae- monetics Research Institute Advanced Component Seminar, Boston, MA 1976. KARSH, JACOB, DANIEL G WRIGHT, JOHN H. KLIPPEL, et al. Lymphocyte Depletion by Continuous Flow Cell Centrifu- gation in Rheumatoid Arthritis. Arthritis and Rheumatism, Vol. 22, No. 10, October, 1979, p. 1055. KILPATRICK D, J FLEMING, C CLYNE, GR THOMPSON. Reduction of Blood Viscosity Following Plasma Exchange. Atherosclerosis, Vol. 32, 1979, p. 301. LOCKWOOD, CM, DK PETERS. The Role of Plasma Exchange and Immunosuppression in the Treatment of Goodpasture’s Syn- drome and Glomerulonephritis. Proceeding of the Haemonetics Research Institute Advanced Component Seminar, Boston, MA 1976. LOCKWOOD, MARTIN, THOMAS PEARSON. Use of Plasma Exchange in Treatment of Allergic Diseases. Proceeding of the Hae- monetics Research Institute Advanced Component Seminar, Boston, MA 1975. NAIK, RB, R ASHLIN, C WILSON. The Role of Plasmapheresis in

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Renal Ttansplantation. Clinical Nephrology, Vol. 11, No. 5 , p. 245.

17. NEWSON-DAVIS, J. Plasma Exchange in Myasthenia Gravis. Plasma Therapy, Vol. 1, No. 2, September, 1979.

18. SWIFT, THOMAS R. Review of Plasma Exchange in the ‘beatment of Myasthenia Gravis. Proceedings of the Haemonetics Research Institute Advanced Component Seminar, Boston, MA 1979.

19. THOMPSON, GR, T SPINKS, A RANICAR, NB MYANT. Non- Steady-State Studies of Low-Densi ty-Leproprotein lhrnover in Familiar Hypercholesterolaemia. Clinical Science & Molecular Medicine (l.Y77), Vol. 52, p. 361.

20. THOMPSON, GR, R LOWENTHAL, NB MYANT. Plasma Exchange in t h e M a n a g e m e n t of Homozygous Fami l i a l Hyper - cholesterolaemia. Lancet, May 31, 1975.

21. WALLACE, DANIEL J, DENNIS GOLDFINGER, e t al. Plasma- pheresis and Lymphoplasmapheresis in the Management of Rheumatoid Arthritis. Arthritis and Rheumatism, Vol. 22, No. 7, July, 1979.

22. BERGER, EDWARD C. The Physiology of Adequate Perfusion. C. V. Mosby, 1979, Part 3.

23. Armour Pharmaceutical Company, Albuminar-25 Product In- formation Sheet. May, 1978.

24. KARSH, JACOB, DANIEL G WRIGHT, JOHN H KLIPPEL, et al. Lymphocyte Depletion by Continuous Flow Cell Centrifugation in Rheumatoid Arthritis. Arthritis and Rheumatism, Vol. 22, No. 10, October, 1979, p. 1055.

Summaries of References From Bibliography

6. BRANDA, R. Plasma Exchange in the Treatment of Immune Thrombocytopenia. Proceedings of the Haemonetics Research Institute Advanced Component Seminar, Boston, MA, 1978. Replacement of removed plasma with equal volume of fresh fro- zen plasma.

7. COBCROFT, R, G TAMAGNIMI, KM DORMANDY. Serial Plas- mapheresis in a Haemophiliac with Antibodies to Factor VIII. Proceedings o f the Haemonetics Research Institute Advanced Component Seminar, London, England, 1977. Patients exchanged eight times over six weeks, removing 1.5 a t each treatment and replacing with normal saline.

8. GILCHER, RONALD 0. Plasma Exchange in Immune and Auto- immune Diseases. Proceedings of the Haemonetics Research In- stitute Advanced Component Seminar, Boston, MA, 1978. Patients had 3L plasma removed and were replaced with 2 parts fresh frozen plasma to 1 part 5% albumin. Reasons fresh frozen plasma chosen were reported as:

a. “Cheaper than 5% albumin.” b. “It is a good source of gamma globulin and therefore would

prevent the depletion of gamma globulin in patients re- ceiving large numbers of plasma exchanges.” “It is a source of complement which might tend to help remove immune complexes opposed t o the consider- ation that the addition of complement might worsen the disorder.” “Fresh frozen is a n excellent source of coagulation factors.”

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