Archives of Disease in Childhood, 1982, 57, 301-308

Current topics

Potential for plasma exchange in childrenE ANGELA E ROBINSONNational Blood Transfusion Service, Regional Transfusion Centre, Leeds

Terminology

Plasmapheresis and plasma exchange are terms thatare often used synonomously in today's literature.However plasma exchange has become possible onlysince the introduction of efficient cell separationtechniques. A cell separator machine can removelarge volumes of plasma, necessitating replacementwith whole or fractionated plasma or a plasmasubstitute, to maintain intravascular colloid osmoticpressure. Plasmapheresis is the removal of plasmaonly, with the return of the cellular blood com-ponents, as first described in 1914.1 The originalterm being derived from the Greek apheresismeaning a withdrawal.

Technique

Plasma exchange is the continuous or discontinuousflow of anticoagulated blood into some form ofcentrifugal device which enables plasma separationto occur. Plasma is removed and an equivalentvolume of replacement material is recombined withthe patient's cells and returned to the patient. Anexample of the continuous flow system is the IBM2997, and of the discontinuous flow system is theHaemonetics Model 30 or V50. Each has its ownparticular advantage, but in a discontinuous flowsystem fluid balance requires more careful manage-ment and it takes longer for a set volume because ofthe intermittent nature of the procedure. The volumeof an exchange and the frequency and duration oftreatment depends entirely on the individual disorder.At present treatment programmes vary enormouslybetween different centres and there is a need forcontrolled studies to establish rational protocols andtherapeutic efficacy in the variety of differentdisorders for which therapeutic plasma exchange hasbeen used.

Rationale ofplasma exchangeThe aims of plasma exchange are (1) Removal ofplasma factors responsible for the causation orprogression of disease. (2) Replacement of deficientplasma factors if the deficiency is causing the

disease. (3) Specific enrichment of plasma factorsnecessary for control of the disease.The majority of current usage falls into category

(1); however recent reports suggest that disordersfalling into category (2) are under investigation,2 butas yet there is little information on category (3) usage.Clinical uses

The Table gives a list of diseases together withreferences to cases in which plasma exchange hasbeen used and for which there may be a paediatricapplication. Most of these studies were undertaken inadults, and reports of therapeutic plasma exchangeundertaken in childhood are few.

It is not the purpose of this review to deal in depthwith each disease but rather to select examples of theprinciples concerned from each group, together withany reports of usage in children.

Table List ofdiseases with references to cases inwvhich plasma exchange has been used

Immunological disordersAntibody mediated

Goodpasture's syndrome3Acquired myasthenia gravis4-6Derniatitis herpetiformis7Idiopathic thrombocytopenic purpura8 13Autoimmune haemolytic anaemia9 10Haemophilia with inhibitorsll-13Rh haemolytic disease of the newborn (maternal treatment)4- 16Bone marrow transplantation across an ABO

incompatible barrier17 18Insulin-resistant diabetes with insulin receptor antibodies'9

Immune complex mediatedSystemic lupus erythematosus20 21Immune complex type of rapidly progressive glomerulonephritis22Cutaneous vasculitis23 24

Presumed immunologicalTransplantation rejection25Disseminated cancer with 'blocking factors'26 27Rheumatoid arthritis28 29Dermatomyositis30Guillain-Barr6 syndrome and the Miller-Fisher variant31-33

Miscellaneous disordersFamilial hypercholesteraemia34Poisoning33 36Refsum's disease37Asthma38Uncontrollable hypertension39Haemolytic uraemic syndrome2 40 41Thrombotic thrombocytopenic purpura42 43Hypogammaglobulinaemia44

301

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

302 Robinson

Immunological disorders

Antibody mediated. The rationale for plasmaexchange in these disorders is removal of theantibody implicated in the aetiology of the disease.

Goodpasture's syndrome (nephritis and lunghaemorrhage)The first major application of plasma exchange inautoimmune disorders was the removal of anti-glomerular basement membrane antibodies foundcirculating in patients with Goodpasture'ssyndrome.3 This is a rare form of rapidly progressiveglomerulonephritis in which the underlying patho-genetic mechanism is partly understood. Anti-glomerular basement membrane antibodies havebeen shown to fix on to glomerular basementmembrane and to crossreact with lung basementmembrane; this antibody when eluted from kidneysof patients with the disease can produce a severe

nephritis in experimental animals.45Since the introduction of a treatment regimen with

intensive daily plasma exchange combined withimmunosuppressive drug therapy (azathioprine or

cyclophosphamide, or both, plus prednisolone) themortality for this disease has been reduced from over

90 to 25 %.46 Immunosuppressive therapy must beused to inhibit further antibody synthesis and tosuppress inflammation. Further suppression ofinflammation is thought to result from using plasmaprotein fraction as the replacement fluid, as this isdevoid of non-specific inflammatory mediators suchas fibrinogen and complement.3 The clinical responseto this regimen appears to correlate well with changesin anti-glomerular basement membrane antibodyconcentration2' and it is recommended that any

patient with this disease showing rapid deteriorationof renal function accompanied by pulmonaryhaemorrhage should have immediate plasmaexchange, for the prognosis worsens once anuria hasoccurred. Although the disease is rare in childhood,cases do occur and a combination ofplasma exchangeand immunosuppression can be successful.47

Idiopathic thrombocytopenicpurpuraSeveral workers have claimed remission of diseaseafter plasma exchange in fulminant idiopathicthrombocytopenic purpura with demonstrable anti-platelet antibodies. A prompt rise in platelets hasbeen achieved after a minimum of one and a

maximum of four plasma exchanges. Novak andWilliams48 described an 8-year-old girl whoseplatelet count responded to one exchange but whodied 48 hours later. In contrast Weir et al.49 reporteda patient who failed to respond; they suggested that acontrolled trial should be carried out. However

fulminant idiopathic thrombocytopenic purpura isfairly rare and if a child presents with catastrophiccomplications, unresponsive to conventional treat-ment, and with demonstrable anti-platelet antibodies,a trial of plasma exchange is not unreasonable.

Haemophilia with circulating inhibitorsThe development of autoantibodies to factor VIII orIX in haemophiliacs can present a major problem inmanagement, particularly if operative proceduresare necessary. Cobcroft et al.'2 showed that pre-operative plasma exchange for the removal ofantibody and replacement with fresh frozen plasmaand factor VIII concentrate enabled restoration ofnormal factor VIII levels, thus permitting anoperative procedure to be undertaken safely. This isan example not only of the removal of the offendingmaterial but also of specific enrichment of theneeded plasma factor. A new approach to thisproblem has been developed by Nilsson et al.50 whichmay have much broader applications. Factor IXantibodies were removed by extracorporeal adsorp-tion of plasma (separated intermittently in aHaemonetics Model 30) on columns of sterileprotein-A-Sepharose, with retransfusion of thetreated plasma. A total of 6 litres of the patient'splasma was depleted of antibodies in this mannerenabling adequate factor IX substitution therapy andsubsequent surgery to be undertaken safely. Thepatient's total immunoglobulin content and specificantibody level decreased to one-fifth of the originalvalues, and in principle this form of treatment couldbe used in patients with other forms of antibodies.

Rh haemolytic disease ofthe newbornIn this situation it is the maternal circulation whichmust be cleared ofthe causative IgG red cell antibodyto protect the fetus from haemolysis. It was Graham-Pole et al.1 who first demonstrated that an intensiveplasma exchange regimen could reduce the maternalanti-D level and the degree of fetal haemolysis,thereby saving affected infants without resort tointrauterine transfusion even if the mother had hadprevious stillbirths. This work has been extended inother centres and has produced a success rate of75% in a series in which the expected stillbirth ratewas 62%.16 As a result plasma exchange startedearly in pregnancy can be recommended as anon-hazardous form of treatment in the managementof severe Rh haemolytic disease.As no concomitant immunosuppressive therapy is

advisable to help control further antibody pro-duction, plasma exchange has to be done about twicea week for a mean period of 131 weeks to maintainlow antibody levels.16 However, should restimulationof the antibody occur by release of fetal Rh

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

D-positive cells into the maternal circulation, andshould the rise in anti-D become impossible tocontrol by plasma exchange alone, the only alter-native is to use intrauterine transfusion. Thisproblem may soon be overcome by the developmentof immunoadsorption columns in which specificremoval of anti-D51 may prove possible.

Immune complex mediated. The logic of using plasmaexchange for the treatment of immune complexdisease is based on the following concepts: removalof the immune complex load, removal of antigen orantibody or both of these, alteration of the size andlattice formation of the immune complex and therebypossibly its pathogenicity, unblocking of thereticuloendothelial system, and the removal ofnon-specific inflammatory mediators.Although the potential role of plasma exchange in

immune complex disease appears greater than inantibody-mediated disease, the results are difficult toassess as many of these diseases are known to havespontaneous fluctuations in activity and mostpatients have been subjected to treatment withmultiple drugs before the use of plasma exchange.

Systemic lupus erythematosus

The removal of immune complexes by plasmaexchange in severe unresponsive systemic lupuserythematosus has been shown to be beneficial.2021Furthermore, studies on the levels of immune com-

plexes in such cases have shown significant reductionsin concentrations after plasma exchange. Theselevels continue to fall beyond the end of the plasmaexchange period, supporting the concept thatclearance of the reticuloendothelial system blockadeis also achieved.5253 Most workers have usedplasma protein fraction as the replacement fluid butMoran et al.54 suggested that patients with systemiclupus erythematosus respond better if fresh frozenplasma is used. They argue that in their 2 patients a

more prolonged relief of symptoms and a betterclearance of immune complexes was achieved byspecific enrichment of complement present in freshfrozen plasma and often deficient in systemic lupuserythematosus. Further data are necessary beforeproper evaluation can be made, particularly asfresh frozen plasma carries the risk of furtherenhancing the inflammatory response by enrichmentwith non-specific inflammatory mediators. Fewcases in children have been reported as systemiclupus erythematosus is rare in them. However,plasma exchange certainly has a place in rapidlyprogressive disease states that are not controlled byconventional drugs, and a course of plasma exchangecombined with immunosuppressive therapy is a

Potential for plasma exchange in children 303

logical step to take in the management of childhoodsystemic lupus erythematosus.

Presumed immunological. The problem with thisgroup of disorders is that the underlying pathogenesisis poorly understood and the use of plasma exchangeis often empirical. Plasma exchange should beregarded as a research procedure until properlycontrolled studies have shown a benefit.

Transplantation rejectionIt is thought that acute vascular rejection may bemediated by humoral antibodies and the removal ofsuch antibodies and other humoral factors by plasmaexchange may help to prevent graft failure. Uncon-trolled studies have been reported recently suggestinga favourable response to plasma exchange but noneshows a statistically significant improvement in theoverall graft survival.5>57 However, two recentlyreported controlled studies58 59 suggest that plasmaexchange exerts no beneficial effect in transplanta-tion rejection episodes and as a result of negativefindings, it is no longer used in one unit.

Juvenile rheumatoid arthritisAs a result of earlier successes in 2 children withsevere connective tissue disease30 60 Brewer et al.6'used plasma exchange to treat 4 children with severejuvenile rheumatoid arthritis, based on the beliefthat circulatory immune complexes and reticulo-endothelial system blockade may be the pathogeneticfactors in this disorder. Plasma exchange wasassociated with partial remission in 2 patients, and acorticosteroid sparing effect permitted normalpubertal growth in one patient who was steroiddependent and dwarfed.There was no improvement in the characteristic

eye lesions and no evidence that progression oferosive arthritis was prevented. One sudden deathoccurred during plasma exchange with fresh frozenplasma, the cause of death appeared related tomicroemboli of unknown nature found in the lungsat necropsy. In view of this episode these workersconclude that plasma exchange in children shouldbe treated as a research procedure and should beperformed only under conditions of intensive care.

Miscellaneous disordersThis group of disorders includes those in whichknown noxious agents are present in excess-forexample cholesterol, poisons, phytanic acid; orthose in which unknown noxious agents may beresponsible for rapid disease progression-forexample asthma and hypertension; or those in whichcertain specific factors are lacking-for example the

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

304 Robinson

haemolytic uraemic syndrome, thrombotic thrombo-cytopenic purpura, or hypogammaglobulinaemia.The aim of plasma exchange is therefore removal ofexcess components or specific enrichment, or both.

HypercholesteraemiaRepeated plasma exchange at weekly or monthyintervals for periods of up to five years in 22 patientswith severe hypercholesteraemia has been shownsafely and effectively to control cholesterol levelsinducing regression of xanthomata and arrest orretardation of atheroma.34Although these results are striking the cost of the

plasma protein fraction used in commercial terms isabout £150 000 (1000 litres). Recently Borberg hasdescribed the use of specific sepharose adsorptioncolumns for the removal of low density lipoproteinsin plasma.62 This new technology could considerablyreduce the cost and may well be more efficient thanthe present method ofmanagement.

PoisoningPlasma exchange can be of benefit in the managementof poisoning if the ingested material is proteinbound and hence non-dialysable-for examplemethyl parathion (a pesticide)35 or mushroompoisoning.36 It has also been used effectively insodium chlorate poisoning (weedkiller) for theremoval of methaemoglobin and the degenerate celldebris produced by this powerful oxidant.63

Mild accidental poisoning in children is common;however severe poisoning is rare and accounts foronly about 15 deaths a year in England and Wales.Many of these fatal cases are due to the tricyclicantidepressants (for example amitriptyline andimipramine), iron, and digoxin, for which thepotential use of plasma exchange in management hasyet to be exploited.

Ninety-six per cent of circulating amitriptyline isreversibly bound to plasma protein and its half-life isbetween 44 and 75 hours; both these facts suggestthat provided plasma exchange is technicallyfeasible, it could prove invaluable in the managementof this type of poisoning. The half-life of imipramineis much shorter (3 j hours), hence plasma exchangewould be of benefit only if used within 3 hours ofingestion.The problems of iron intoxication are created by

the direct toxic effect of iron on the gastrointestinaltract leading to direct access to the portal circulationwithout transport across the intestinal mucosa.

This results in toxic levels of unbound serum iron,and although this is chelatable, continued release offree iron from its protein bound state necessitatesrepeated doses of desferrioxamine. If a combinedtherapeutic approach of chelation therapy and

plasma exchange were used, more rapid controlmight be achieved and previously unsalvagable casesbe rescued.The potential use of plasma exchange in digoxin

intoxication is more difficult to predict as it israpidly distributed to the tissues and is preferentiallybound to the myocardium at a ratio of 200:1compared with the amount circulating. Althoughonly 25% of circulating digoxin is protein bound, itshalf-life is between 34 and 51 hours and plasmaexchange could therefore provide a useful means ofremoving any remaining circulating digoxin before itbecomes irreversibly tissue bound and thereby serveas a useful adjunct to more conventional therapy.

Refsum's disease (heredopathia atactica polyneuriti-formis)This is an autosomal recessive lipid storage disordercharacterised by chronic polyneuropathy, retinitispigmentosa, and icthyosis with raised blood levels ofphytanic acid due to failure of or-oxidation of thisfatty acid. Exacerbation of the disease correlateswith a rise in blood level of phytanic acid, andimprovement with a fall. Treatment in the past hasbeen mainly by diet, but Gibberd et al.37 recentlyachieved a good response in one patient by usinglarge volume plasma exchange combined with a dietlow in phytanic acid but of a high calorific value,thereby preventing mobilisation of phytanic acidfrom fat stores.

Early diagnosis and treatment of this disease bydiet, and if necessary by plasma exchange, could leadto good long-term survival provided retinitispigmentosa has not developed as this is irreversible.

Haemolytic utraemic syndromeRecent hypotheses concerning the pathogenesis ofhaemolytic uraemic syndrome and thromboticthrombocytopenic purpura suggest the absence of aplasma factor needed for prostacyclin production byvascular endothelium, or the presence of a circulatinginhibitor to its production, or both of these.2 64 Thebelief being that defective prostacyclin activityfavours the formation of platelet thrombi in themicrocirculation, a finding typical of haemolyticuraemic syndrome and allied disorders. Tworecently reported cases in which therapeutic plasmaexchange with fresh frozen plasma as the replacementfluid was used in the management of childhoodhaeTnolytic uraemic syndrome appear to support thishypothesis.40 41 However the use of therapeuticplasma exchange for haemolytic uraemic syndromeshould be reserved for children in whom theprognosis is poor, as our experience in the Leedspaediatric nephrology unit during the last 10 years

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

Potential for plasma exchange in children 305

has been a mortality rate of less than 5% for childrenaged under 5 years. In both cases reported, plasmaexchange was used during a recurrent phase of thedisease, a recognised poor prognostic factor, althoughboth children were under 5 at their initial pre-sentation.4041 If conventional forms of treatmentfail to resolve the life threatening situation of severethrombocytopenia, haemolytic anaemia, and hyper-tension, rapid resort to therapeutic plasma exchangemay prove to be a rational and life-saving alternativein the management of severe haemolytic uraemicsyndrome.

Problems

Plasma exchange is a fairly safe procedure with fewadverse effects provided it is undertaken in anexperienced unit. The most commonly encounteredproblems are citrate toxicity, management of fluidand electrolyte balance, hazards associated with thereplacement fluids, and vascular access.

Anticoagulant. Citrate is the most commonly usedanticoagulant in all cell separation techniques andtemporary hypocalcaemia can be a recurringproblem unless measures are taken to avoid it.65

Fluid and electrolyte balance. If there is impairedrenal function exact fluid and electrolyte balance areof paramount importance. As most of these patientsare incapable of responding to any fluid or electrolyteimbalance during plasma exchange, care must betaken to ensure that the colloid osmotic pressure andthe electrolyte content of any replacement fluid arewithin physiological limits. In childhood, volumechanges pose a particular problem as the extra-corporeal circulatory volume must be kept withinthe toleration limits of the child-that is less than15% of the total blood volume to avoid hypotensiveepisodes. To minimise blood volume changes specialpaediatric equipment or the addition of red cell andfluid supplements to the extracorporeal circuit maybe necessary.

Replacement fluids. Plasma protein fraction andfresh frozen plasma are the main replacement fluidsused. Fresh frozen plasma has the advantage ofbeing cheap; it is readily obtainable and helps tomaintain normal immunoglobulins, coagulationfactors, and complement components but it has thedisadvantage that it can cause allergic reactions,citrate load, and can transmit hepatitis andsensitisation to proteins. Allergic reactions to freshfrozen plasma are not uncommon and other workersas well as ourselves have found a higher incidence inalloimmunised individuals and in patients with

autoimmune disorders than in the general hospitalpopulation.26

Anaphylaxis is a serious hazard and unless freshfrozen plasma has been shown to have a therapeuticadvantage over plasma protein fraction its use is notrecommended. Plasma protein fraction does notappear to be allergenic and is free from the risk oftransmitting hepatitis and sensitisation to protein; itis also devoid of inflammatory mediators. It has thedisadvantage of being expensive and in short supplyand when used in large volume exchanges it can giverise to a transient coagulopathy. It is also deficient inpseudocholinesterase which could give rise to aprolonged episode of suxamethonium-inducedapnoea during anaesthesia unless fresh frozenplasma replacement is used before any anaestheticprocedure.66 Hypotension in response to the rapidinfusion of plasma protein fraction is seenoccasionally in the USA and Australia, but this hasnot been reported in Europe and slight variations inmethods of production must be responsible for thesedifferences.

Occasionally combinations of commercial plasmaexpanders and plasma protein fraction or freshfrozen plasma have been used, but this generallygives rise to protein depletion and transient coagulo-pathy; some allergic reactions have also beenreported.

Vascular access. A major problem encountered inchildhood is adequate vascular access. This isessential to ensure a reasonable blood flow into thecell separator machine, otherwise plasma exchangecannot be undertaken. In the majority of cases intra-arterial or central venous lines or arteriovenousshunts have to be inserted with all their attendantrisks.From the foregoing list of problems it can be seen

that plasma exchange in childhood is a more difficultand hazardous procedure than in adults. This mayaccount for its fairly limited usage to date inpaediatric practice. However its potential is excitingprovided a rational approach is taken and itslimitations are realised.

Limitations

Transient effect. Unless plasma exchange is used toremove short-lived non-recurring specific noxiousagents-for example poisons-it can be regardedonly as an emergency therapeutic measure used tointerrupt a disease process whether mediated byantibodies, immune complexes, non-specific inflam-matory mediators, or by other as yet unspecifiedhumoral agents-either a lack of them or an excess.The rationale being the prevention of further

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

306 Robinson

irreversible tissue damage occurring before moreconventional treatment-such as drug im.muno-suppression-has become effective or before thedamaged tissue or organ has had time to recover.Occasionally long-term treatment is indicated-forexample in hypercholesteraemia-but this is apracticable proposition only if the interval betweenexchanges can be lengthened while still maintainingtherapeutic benefit. At present plasma exchange is afairly crude form of treatment, but with the advent ofadsorption columns future prospects are brightermaking the method more specific and obviating theneed for any substitution fluid. The whole procedurethen becomes cheaper, safer, and more satisfactory.

Cost

As therapeutic effectiveness is difficult to ascertain,the cost of the procedure must be taken into con-sideration. The current cost of undertaking oneplasma exchange in childhood in terms of disposableequipment and plasma protein fraction used, is in theregion of £150. This figure does not take into accountthe capital and revenue expenditure incurred bythe running of an efficient cell separator unit;without experienced staff the procedure is impossibleto carry out. It is foolhardy and potentially hazardousto attempt therapeutic cell separation proceduresonly occasionally with an inexperienced team, butthe costs ofrunning such units are high.

Conclusion

Plasma exchange is an exciting field which has givena new therapeutic approach to a variety of differentdisorders. Furthermore it has opened up thepossibility of a combined approach using adsorptioncolumns for the removal of the specific unwantedsubstance. By enabling the enrichment or depletionof a particular substance in the circulation it can beused as an investigative tool in the study of thatsubstance's role in the disease process.

It is important that such studies are undertaken inunits in which full laboratory assessment is possibleand that controlled trials are undertaken in diseaseswhere the therapeutic efficacy of plasma exchange isin doubt. To quote from a recently written article onplasma exchange, 'Its excessive use beyond itsnatural limitations could overshadow its intrinsicmerits and hasten its decline.'"

References

Abel J J, Rowntree L G, Turner B B. Plasma removalwith return of corpuscles (plasmapheresis). J PharmacolExp Ther 1914; 5: 625-41.

2 Remuzzi G, Marchesi D, Mecca G, et al. Haemolyticuraemic syndrome: deficiency of plasma factor(s)regulating prostacyclin activity? Lancet 1978; ii: 871-2.

3 Lockwood C M, Rees A J, Pearson T A, Evans D J,Peters D K, Wilson C B. Immunosuppression and plasmaexchange in the treatment of Goodpasture's syndrome.Lancet 1976; i: 711-5.

4Pinching A J, Peters D K, Newsom Davis J. Remission ofmyasthenia gravis following plasma exchange. Lancet1976; ii: 1373-6.

5 Dau P C, Lindstrom J M, Cassel C K, Denys E H,Shev E E, Spitler L E. Plasmapheresis and immuno-suppressive drug therapy in myasthenia gravis. N Engl JMed 1977; 297: 1134-40.

6 Newsom Davis J, Wilson S G, Vincent A, Ward C D.Long term effects of repeated plasma exchange inmyasthenia gravis. Lancet 1979; i: 464-8.

7Carruthers J A, Ewins A R. Herpes gestationis: studies onthe binding characteristics, activity, and pathogeneticsignificance of the complement fixing factor. Clin ExpImmunol 1978; 31: 38-44.

8 Branda R F, Tate D Y, McCullough J J, Jacob H S.Plasma exchange in the treatment of fulminant idiopathic(autoimmune) thrombocytopenic purpura. Lancet 1978;i: 688-90.

9Branda R F, Moldow C F, McCullough J J, Jacob H S.Plasma exchange in the treatment of immune disease.Transfusion 1975; 15: 570-6.

10 Patten E, Reuter F P. Evans' syndrome: possible benefitfrom plasma exchange. Transfusion 1980; 20: 589-93.

11 Pintado T, Taswell H F, Bowie E J W. Treatment of lifethreatening hemorrhage due to acquired factor VIIIinhibitor. Blood 1975; 46: 535-41.

12 Cobcroft R, Tamagnini G, Dormandy K M. Serialplasmapheresis in a haemophiliac with antibodies F VIII.J Clin Pathol 1977; 30: 763-5.

13 Isbister J P, Biggs J C, Penny R. Experience with largevolume plasmapheresis in malignant paraproteinaemiaand immune disorders. Aust NZJ Med 1978; 8: 154-64.

14 Clarke C A, Bradley J, Elson C J, Donohoe W T A,Lehane D, Hughes-Jones N C. Intensive plasmapheresisas a therapeutic measure in rhesus-immunised women.Lancet 1970; i: 793-8.

15 Graham-Pole J, Barr W, Willoughby M L N. Continuousflow plasmapheresis in management of severe rhesusdisease. Br MedJ 1977; i: 1185-8.

16 Robinson E A E, Tovey L A D. Intensive plasma exchangein the management of severe Rh disease. Br J Haematol1980; 45: 621-31.

17 Gale R P, Feig S, Ho W, Falk P, Rippee C, Sparkes R.ABO blood group system and bone marrow transplan-tation. Blood 1977; 50: 185-94.

18 West N C, Clink H M, Powles R. Plasma exchange beforemarrow transplant. In the proceedings of the IBMSymposium on the Clinical Aspects of Cell Separation,London 1981.

19 Muggeo M, Flier J S, Abrams R A, Harrison L C,Deisserroth A B, Kahn C R. Treatment by plasmaexchange of a patient with auto-antibodies to the insulinreceptor. N EnglJ Med 1979; 300: 477-80.

20 Verrier Jones J, Cumming R H, Bucknall R C, et al.Plasmapheresis in the management of acute systemiclupus erythematosus?Lancet 1976; i: 709-11.

21 Lockwood C M, Pussell B, Wilson C B, Peters D K.Plasma exchange in nephritis. Adv Nephrology 1979; 8:383-418.

22 Lockwood C M, Rees A J, Pussell B A, Peters D K.Experience of the use of plasma exchange in the manage-ment of potentially fulminating glomerulonephritis andSLE. Exp Hematol 1977; 5: Supplement, 117-36.

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

Potential for plasma exchange in children 307

23 Pussell B A, Lockwood C M, Scott D M, Pinching A J,Peters D K. Value of immune complex assays in diagnosisand management. Lancet 1978; ii: 359-65.

24 Valbonesi M, Garelli S, Mosconi L, Camerone G,Bedarida G, Di Guardo G. Plasma exchange in themanagement of a patient with diffuse necrotizingcutaneous vasculitis. Vox Sang 1980; 39: 241-5.

25 Cardella C J, Sutton D M C, Falk J A, Katz A, UldallP R, de Veber G A. Effect of intensive plasma-exchangeon renal transplant rejection and serum cytotoxic anti-body. Transplant Proc 1978; 10: 617-9.

26 Israel L, Edelstein R, Mannoni P, Radot E, GreenspanE M. Plasmapheresis in patients with disseminatedcancer: clinical results and correlation with changes inserum protein. The concept of 'non-specific' blockingfactors. Cancer 1977; 40: 3146-54.

27 Hobbs J R, Byrom N, Elliot P, Oon C J, Retsas S. Cellseparators in cancer immunotherapy. Exp Hematol1977; 5: Supplement, 95-103.

28 Wallace D J, Goldfinger D, Gatti R, et al. Plasmapheresisand lymphoplasmapheresis in the management ofrheumatoid arthritis. Arthritis Rheum 1979; 22: 703-10.

29 Rothwell R S, Davis P, Gordon P A, et al. A controlledstudy of plasma exchange in the treatment of severerheumatoid arthritis. Arthritis Rheum 1980; 23: 785-90.

30 Brewer E J, Jr, Giannini E H, Rossen R D, Patten B,Barkley E. Plasma exchange therapy of a childhood onsetdermatomyositis patient. Arthritis Rheum 1980; 23:509-13.

31 Brettle R P, Gross M, Legg N J, Lockwood M, Pallis C.Letter: Treatment of acute polyneuropathy by plasmaexchange. Lancet 1978; ii: 1100.

32 Littlewood R, Bajada S. Successful plasmapheresis in theMiller Fisher syndrome. Br MedJ 1981; 282: 778.

33 Valbonesi M, Garelli S, Mosconi L, Zerbi D, Celano I.Plasma exchange as a therapy for Guillain-Barr6 syndromewith immune complexes. Vox Sang 1981; 41: 74-8.

34 Thompson G R. Plasma exchange for hypercholesterae-mia. Lancet 1981; i: 1246-8.

35 Luzhnikov E A, Yaroslavsky A A, Molodenkov M N,Shurkalin B K, Evseev N G, Barsukov U F. Letter:Plasma perfusion through charcoal in methylparathionpoisoning. Lancet 1977; i: 38-9.

36 Lembeck F, Beubler E, Lepuschutz H J, Stolze A.Plasmaphorese zur Elimination toxischer Stoffe mit hoherPlasmaproteinbindung. Wien Klin Wochenschr 1976; 89:257-60.

37 Gibberd F B, Page N G R, Billimoria J D, Retsas S.Heredopathia atactica polyneuritiformis (Refsum'sdisease) treated by diet and plasma exchange. Lancet1979; i: 575-8.

38 Gartmann J, Grob P, Frey M. Letter: Plasmapheresis insevere asthma. Lancet 1978; ii: 40.

39 Whitworth I A, d'Apice A J F, Kincaid-Smith P, ShulkesA A, Skinner S L. Letter: Antihypertensive effect ofplasma exchange. Lancet 1978; i: 1205.

40 Beattie T J, Murphy A V, Willoughby M L N, MachinS J, Defreyn G. Plasmapheresis in the haemolytic-uraemic syndrome in children. Br Med J 1981; 282:1667-8.

41 Sweny P, Winning A, Gross M L P, Moorhead J F.Letter: Plasmapheresis in the haemolytic-uraemicsyndrome in children. Br MedJ 1981 ; 282: 2137.

42 Bukowski R M, King I W, Hewlett J S. Plasmapheresisin the treatment of thrombotic thrombocytopenicpurpura. Blood 1977; 50: 413-7.

43 Okuno T. Letter: Plasmapheresis for thrombocytopenia.Lancet 1978; i: 1095.

44 Pussell B A, Lockwood C M. Plasma exchange in

immunological disorders. IBM Medical Review 1980; 2:22-9.

45 Dixon F J, Feldman J D, Vazquez J J. Experimentalglomerulonephritis: the pathogenesis of a laboratorymodel resembling the spectrum of human glomerulo-nephritis. J Exp Med 1961; 113: 899-920.

46 Kincaid-Smith P, d'Apice A J F. Plasmapheresis inrapidly progressive glomerulonephritis. Am J Med 1978;65: 564-6.

47 Siegler R L, Bond R E, Morris A H. Treatment ofGoodpasture's syndrome with plasma exchange andimmunosuppression. Clin Pediatr (Phila) 1980; 19:488-91.

48 Novak R, Williams J. Plasmapheresis in catastrophiccomplications of idiopathic thrombocytopenic purpura.JPediatr 1978; 92: 434-6.

49 Weir A B, Poon M C, McGowan E I. Letter: Plasmaexchange for idiopathic thrombocytopenic purpura.Lancet 1978; ii: 689.

50 Nilsson Inga M, Jonsson S, Sundqvist S-B, Ahlberg A,Bergentz S-E. A procedure for removing high titer anti-bodies by extracorporeal protein-A-Sepharose adsorptionin hemophilia: substitutiontherapy and surgeryin apatientwith hemophilia B and antibodies. Blood 1981; 58: 38-44.

51 Jonsson S, Hakansson L. Extracorporeal affinity chroma-tography of blood plasma over agarose beads. In theproceedings of the Fourth International Conference onApplied Affinity Chromatography and Allied Techniques,Sweden 1981.

52 Verrier Jones J. Plasmapheresis: great economy in the useof horses. N EnglJ Med 1977; 297: 1173-5.

53 Pussell B A, Lockwood C M, Bartolotti S R, Peters D K.Plasma exchange in immune-complex disease andGoodpasture's syndrome. In the proceedings of a Work-shop on Plasma Cytapheresis, Mayo Clinic, April 1979.

54 Moran C J, Parry H F, Mowbray J, Richards J D M,Goldstone A H. Plasmapheresis in systemic lupuserythematosus. Br MedJ 1977; i: 1573-4.

55 Rifle G, Chalopin J M, Turc J H, et al. Plasmapheresis inthe treatment of renal allograft rejections. TransplantProc 1979; 11: 20-6.

56 Adams M B, Kauffman H M, Herbert L A, Hussey C V,Duquesnoy R J, Tomasulo P A. Plasmapheresis in thetreatment of renal allograft rejection. Proc Clin DialTransplant Forum 1979; 9: 252-3.

57 Cardella C J, Sutton D M C, Falk J A, Katz A, UldallP R, deVeber G A. Intensive plasma exchange, comple-ment dependent microcytotoxicity, and renal transplantrejection. Proc Eur Dial Transplant Assoc 1977; 14:328-35.

58 Kirubakaran M G, Disney A P S, Norman J, Pugsley D J,Mathew T H. A controlled trial of plasmapheresis in thetreatment of renal allograft rejection. Transplantation1981; 32: 164-5.

59 Power D, Nicholls A, Muirhead N, et al. Plasma exchangein acute renal allograft rejection: is a controlled trialreally necessary? Transplantation 1981; 32: 162-3.

60 Birdsall H H, Brewer E J, Rossen R D, Moake J L.Clinical improvement associated with hypocomple-mentemia following plasmapheresis. In: Dau P C, ed.Plasmapheresis and the immunobiology of myastheniagravis. Boston: Houghton Mifflin, 1978: 191-8.

61 Brewer E J, Jr, Nickeson R W, Jr, Rossen R D, PersonD A, Giannini E H, Milam J D. Plasma exchange inselected patients with juvenile rheumatoid arthritis.JPediatr 1981; 98: 194-200.

62 Borberg H. New perspectives in plasma exchange therapy.In the proceedings of the Advanced Blood ComponentSeminar. Haemonetics Research Institute EuropeanMeeting, Montreux, July 1981.

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from

308 Robinson

63 Davison A M, Mascie-Taylor B H, Robinson A, BarnardD L. The use of plasma exchange, transfusion, andhaemodialysis in the management of sodium chlorateintoxication. In: Sieberth H G, ed. Proceedings of theInternational Symposium on Plasma Exchange, Cologne,June 1980. Stuttgart: Schattauer, 1980: 373-4.

64 Anonymous. Platelets, endothelium, and renal disease.Lancet 1979; ii: 890-1.

65 Watson D K, Penny A F, Marshall R W, Robinson E A E.Citrate induced hypocalcaemia during cell separation.Br J Haematol 1980; 44: 503-7.

66 Evans R T, Macdonald Rosemary, Robinson Angela.Suxamethonium apnoea associated with plasmapheresis.Anaesthesia 1980; 35: 198-201.

Correspondence to Dr E A E Robinson, NationalBlood Transfusion Service, Regional TransfusionCentre, Bridle Path, Leeds LS15 7TW.

Received 17 November 1981

The following articles will appear in future issues of this journal:

Early rise in 'pitted' red cell count as a guide to susceptibility to infection in childhood sickle cell anaemiaD W Rogers, B E Serjeant, and G R Serjeant

Milk antigen absorption in the preterm and term neonateD M Roberton, R Paganelli, R Dinwiddie, and R J Levinsky

IgE screening in 1701 newborn infants and the development of atopic disease during infancyS Croner, N-I M Kjellman, B Eriksson, and A Roth

Outcome for newborn babies declined admission to a regional neonatal intensive care unitD G Sims, J Wynn, andML Chiswick

Value of computerised tomography in children with non-specific mental subnormalityS Lingam, S Read, IM Holland, J Wilson, EM Brett, and R D Hoare

Defective yeast opsonisation and functional deficiency of complement in sickle cell diseaseV F Larcher, R J Wyke, L R Davis, C E Stroud, and R Williams

Cigarette smoking among secondary schoolchildren 1975-79R G Rawbone and A Guz

on March 22, 2020 by guest. P

rotected by copyright.http://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.57.4.301 on 1 A

pril 1982. Dow

nloaded from