PLASMA EXCHANGES

DEFINITION

BASIS

INDICATIONS

CONTRA-INDICATIONS, SIDE EFFECTS
IF YOU WANT TO LEARN MORE..
FAQ PATIENTS: WHAT IS IT?; Apheresis procedure ( = blood components separation ) consisting in plasma extracting :; - small volumes (600 ml max : plasmapheresis still used for plasma donation).; - large volumes ( 2 to 5 liters ): plasma exchange with volume balanced by replacement fluids used for treatment.

1. MAIN ASPECTS

1.1. Technical aspects

- extracorporeal line (EL)

It is made of a sterile, apyrogenic single-use kit, with an outside volume of 250 to 500 cc. The line has to be prepared before session (rinsing, purging with saline solution), there is a filling in time of the line before process and a filling out time of the line at the end.

- separation plasma / blood cells :

2 principles mais 3 processes :. discontinued flow centrifugation ( centrifugation bowl with subsequent input and output cycles )

. continued flow centrifugation (centrifugation ring with permanent in and out flow )

. filtration : separating device with a porous membrane

- venous lines :

two accesses are mandatory (input line "artery" from patient to device and return line "vein" from device to patient) except in discontinued centrifugation flow where in and out cycles may alternate on a single veinous access. Filtration requires 2 accesses and higher flow rate.

- anticoagulation :

citrate saline solutions (ACD) or heparin

- automation/safety :

First cell separators were worked manually : preparation, data of session and extraction/replacement balance. Now monitors are computer controlled and handler is assisted through the whole procedure. The patient safety is provided by pumps and manometric panels, air detectors.

- plasma treatment (optional):

Extracted plasma may be treated (selective clearing) and "good molecules" spared and returned to the patient.; An ancillary line feeds another device that may be:; . a plasmafilter retaining "High molecular weight" proteins (involved in some diseases and sparing the patient's albumin) : "cascade filtration"; . a cationic resin absorbing biliary salts; ( indicated in cholestatic diseases ).; . a Protein A column : retaining IgG; . anti-apo B immuno-absorption column : clears the VLDL, LDL in hypercholesterolemias; Some other procedures are still experimented ( cryoprecipitation, electrophoresis, immuno-adsorption)

1.2. Replacement fluids

they are plasma substitutes, they should have :; - a prolonged volemic expanding potential; - no decay effects on hemostasis; - no infectious potential; - a moderate price
: Colloidal solutes are prefered : modified gelatins, hydroxyethylstarch) in restricted volume ( 20 ml/kg) + completed by a 4% human albumin solution.; Fresh frozen plasma is only indicated in case of major hemostasis disorders and thrombotic microangiopathy..

1.3. Researched effects

- short term effects :

. clearing of circulating harmful components (protein bound toxics, monoclonal gammaglobulins, circulating immune complexes)

. vascular rheologic parameters improvement ( particularly aimed in vasculitis and microcirculation impairment )

- mid term effects :

clearing properties of PE relieve the macrophagic sytem cells in dysimmune disease, hitherto increasing their ability to remove immunoglobulin and immune complexes,

By removing antibodies PE could amplify their secreting cells sensitivity to immunosuppression drugs (some autoimmune diseases with auto-antibodies )

- long term effects (poorly known) :

immuno-modulation
: globally PE clear plasma protein or protein bound toxics and generate quick immunosuppression. They are of limited use in diseases where a rapid removal of high molecular weight toxics and immunosuppression is aimed (often associated to immunosuppressive drugs)

1.4. what volume, how often ?

This curve shows the achieved concentration of a plasma component (C) after exchange of a given plasma volume V, relation is exponential. With only one body plasma mass (MP), more than 50 % of the component is cleared ; beyond, the volume to process increases widely for a little gain. Most PE monitors have a programmed volume, generally agreed at 1,3 MP that removes a component at 72 %.; In fact immunological active components aimed by PE have different intra/extravascular distribution rates, various synthesis and self-clearing levels. After PE, concentration of a component with mixed intra/extra vascular distribution takes the following aspect :

: According to the component to remove (synthesis level, vascular distribution, aimed effects ) frequency of sessions are increased or decreased rather than modifying processed volumes, for instance:
- IgM are mainly intravascular with short half life ( 5 days ) : periodic sessions.: - IgG have a mixed distribution, a long half life ( 22 days ) : more frequent sessions
- Immune complexes have various behaviour but repeated PE increase their natural clearance ( effects on macrophages ): - Auto-Antibodies : In this case of permanent antigen stimulus (secondary response), PE lead to a synthesis rebound effect requiring intensified treatment associated to immunosuppression drugs with a probable sensitizing of the autoreactive clones.
Inflammation active components, cytokines : PE reduce their activity but transiently, needing more often sessions associated to steroids.

2. TREATMENT INDICATIONS

Indications of this costly treatment have been dramatically restricted and still under discussion.
: We may consider :
:: Group A : PE as first line treatment (A1) or after other treatments failure (A2) endorsed by controlled studies (A1a, A2a) or numerous open studies leading to general agreement (A1b, A2b); Group B : PE are still submitted to discussion regarding each case or are still assessed through trials.

2.1. Group A

- severe forms of thrombotic micro-angiopathies (Moscovitz disease and thrombotic thrombocytopenic purpura) (A1a)
- neurolupus (± brain vasculitis)(A1b): - hyperviscosity syndrome related to monoclonal gammapthies with neurological and/or hemorragic manifestations (A1b)
- hypercholesterolemia type IIa homozygotic (A1b): - clearing cytotoxic antibodies before transplantation (A1b)
- cryoglobulinemia (neurological or renal involvement) (A1b): - Refsum's disease (A1b)
- Guillain Barré Syndrome (A2a); - Chronic polyradiculonevritis (A2a)
- IgA or IgG MGUS related neuropathy (A2a): - Renal failure in myeloma (A2a); - IgA glomerulonephritis (A2b; - anticoagulant inhibitors (A2b); - chronic cholestatic disease (A2b)
- Goodpasture syndrome (A2b): - myasthenia gravis ou Lambert Eaton syndrome (A2b)
- Post transfusionnal thrombocytopenic purpura (A2b)

2.2. Group B

- IgM monoclonal related neuropathy: - Multiple sclerosis; - Connective tissue diseases : periarteritis nodosa (PAN) related to B hepatitis, necrosis vasculitis, dermato/polymyositis, Schenoch Henlein purpura,..; - Auto-immune diseases : thrombocytopenic purpura, cold agglutinin hemolytic disease, uveitis, antiphospholipid syndrome...
- Metabolic disease : resistant heterozygotic hypercholesterolemia, thyrotoxic crisis...: - Poisoning (phalloïdin, digitalin, botulism)

3. CONTRA-INDICATIONS

3.1. related to extracorporeal line and anticoagulation

- precarious hemodynamics (cardiogenic shocks)

- unstabilized angina pectoris

- pericardic effusion (heparin)

3.2. Related to immunosuppression

- non controlled infectious diseases (septicemia)

4. SIDE EFFECTS

4.1. Immediate :

* related to extracorporeal line and anticoagulation :

- vagus nerve syndrome, low or high blood pressure.

- veinous puncture hazards, air embolism.

- excessive bleeding, allergy ou thrombopenia induced by heparin, citrate poisoning with hypocalcemia manifestations (headache-cramps-swarming-tetanus rarely cardiac arythmia).

* related to replacement fluids :

- chills-fever

- nausea-vomiting, diarrhea (albumin)

4.2. delayed :

* impaired hemostasis :

- hypocoaguable state 8-12 hours after session

- hypercoaguable state 24-72 hours by rebound effect (antithrombin 3 synthesis delayed)

-> THROMBOSIS RISK increased especially when other promoting conditions (inflammation, confinement to bed)

Preventive heparin treatment with normal coagulation tests objective is the rule in these conditions.

* Immunosuppression :

Particular sensitivity to bacterial infections (humoral immunity deficiency)

* transfusion related infection :

Has not been reported since the exclusive use of viro-inactivated, heat treated (Albumin) or artificial substitutes.

IF YOU WANT TO LEARN MORE:

Basics

Coagulation Disorders with plasma exchange.
Simon L. et al.,
Plasma Ther Transfus Technol 1982; 3: 147-152 Immunological effects of plasmapheresis synchronized with pulse cyclophosphamide.
Dau P. et al.,
J Rheumatol. 1991; 18: 270-276
Reticuloendothelial system Fc receptor function and plasmapheresis in systemic lupus erythematosus.
Hamburger M. et al.,
Artif. Org. 1981; 5: 264-268 Role of replacement fluids in the immediate complications of plasma exchange
Korach J.M. et al.,
Intensive Care med 1998; 24: 452-458

hematology

Hyperviscosity syndrome in paraproteinemeia managed by plasma exchange; monitored by serum tests.
Beck J.R. et al.,
Transfusion 1982; 22(1): 51-54 Comparison of plasma exchange with plasma infusions in the treatment of thrombotic thrombocytopenic purpura
Rock A. et al.,
N. Engl. J. Med. 1991; 325: 393-397
Accelerated recovery from immune-mediated thrombocytopenia with plasmapheresis.
Porter CG et al.,
Am. J. Med. 1985; 79: 765-76

nephrology

Controlled plasma exchange trial in acute renal failure due to multiple myeloma.: Zucchelli et al.,
Kidney Internat. 1988; 33: 1175-1180
Treatment of renal failure associated with multiple myeloma.
Johnson W. et al.,
Arch. Intern. Med. 1990; 150: 863-869
Successful removal and prevention of resynthesis of anti-HLA antibody.
Taube D.H. et al.,
Transplant. 1984; 37: 254-255
Plasma exchange in severe gastro-intestinal and renal forms of Henoch Schönlein purpura and primary IgA nephropathy. Review of the literature and results of a french retrospective study.
Alcalay D. et al.,
Plasma Ther Transfus Technol 1987; 8: 147-160
Retrospective study of plasma exchange in patients with idiopathic rapidly progressive glomerulonephritis and vasculitis.
Gianviti A. et al.,
Arch Dis Child 1996; 75: 186-190
A controlled trial of plasmapheresis therapy in severe lupus nephritis.
Lewis E. et al.,
N. Engl. J. Med. 1992; 326: 1373-1379

neurology

Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy.
Dyck P.J. et al.,
N. Engl. J. Med. 1986; 314: 461-465
Plasma exchange and chlorambucil in polyneuropathy associated with monoclonal IgM gammopathy.
Oksenhendler E. et al.,
J Neurol Neurosurg Psychiatry 1995; 59(3): 243-247
Plasma exchange in polyneuropathy associated with monoclonal gammapathy of undetermined significance
Dyck P.J. et al.,
N. Engl. J. Med. 1991; 325: 1482-1486
Meta-analysis of clinical studies of the efficacy of plasma exchange in the treatment of chronic progressive multiple sclerosis.
Vamvakas E. et al.,
J Clin Apheresis 1995; 10(4):163-170
Randomised trial of plasma exchange, intravenous immunoglobulin and combined treatments in Guillain-Barré syndrome.
Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group.
Lancet 1997; 349: 225-230
Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis.
Gajdos P. et al.,
Ann Neurol 1997; 41(6): 789-796

Internal medicine

Guillevin L. et al.,: Arthritis and Rheum. 1992; 35: 208-214

Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis.
Guillevin L. et al.,: Arthritis and Rheum. 1995; 38:1638-1645

Long term application of three types of sorbents for LDL apheresis.
Kukharchuk V. et al.,
Plasma Ther Transfus Technol 1988; 9: 45-47
Guidelines for the management of essential mixed cryoglobulinemia.
Tavoni A. et al.,
Clin Exp Rheumatol 1995; 13 Suppl 13(): 191-195
Hemapheresis in systemic lupus erythematosus.
Rifle G. et al.,
Clin. Exp. Rheumatol. 1990; 8 Supp(5): 51-55

PATIENTS: You are a patient and you have to undergo plasma exchange therapy, you may have the following questions...; Q - My blood has to be "cleaned"... are my kidneys sick ? how long ? how often ?; A - It is DIALYSIS that treats patients with impaired renal fonction sometimes definitely, with a thrice a week contraint for ever. Dialysis removes water and small molecules (urea,..).; Plasma exchange (PE) removes plasma, does not roughly alter blood cells or hydro-electrolyte components. Unless you need PE for hypercholesterolemia, this treatment is always transient from a few days to a couple of months with sometimes only one session per week.; Q - What does a session consist in? Shall I need to stay in hospital ? to have a veinous catheter ? Is it painful ?; A - As far as your general condition is affected by your disease, plasma exchange may be conducted for outpatients (day hospital).; If your arm veins are sufficient, the nurse will proceed to the puncture of 2 veins (1 for output, 1 for input) with a needle similar to those used for blood donation. If not, a central veinous line is placed by a physician with local anaesthetic.; These are the only painful aspects, for the rest of the session the only uncomfort will consist in keeping a standstill during 2 to 3 hours.; After session you shall stand up progressively, may have a meal and go back home but you may be tired during days of treatment.; Q - What are the side effects of this treatment during and after session ?, plasma products were mentionned : are they safe ? my immunity will be suppressed, what is the risk ?; A - Plasma exchange is well tolerated (3 to 8 % of minor hazards), the most common side effect is feeling cold, chills and other reactions are not serious and will be relieved easily by appropriated measures.; Your plasma is replaced by artificial solutes and human albumin. The latter is a heat treated product, widely used for nearly 20 years and has never been involved in any infectious disease. Also the whole line containing your blood is a sterile, single use and discardable device.; This treatment will discard some of your antibodies, it is often the aim of PE and this will make you more vulnerable to infections. In this case, you will probably take also immunosuppressive drugs enhancing this objective. If you experience fever, cough, digestive upset, warn rapidly your physician.; Q - I am appointed to my first session, what shall I inform the doctor of ? what shall I plan ? may I work after ?; A - Inform the physician of your past medical history especially heart and vascular disease, thrombosis and eventual allergy (heparin for instance), other treatments. If you experience present infectious symptom, warn the doctor. If you feel stressed or anxious, the doctor may propose some relaxing medication before session.; No need to be fasting, a light meal is even recommended. If you are treated for blood pressure or heart disease, take your drugs as usual the days of session.; For a first session, plan to be accompanied returning home and plan the whole day free in case you need rest.; If sessions are well tolerated and not too frequent, you may keep up with your occupational activities.