[Plasma exchange--plasma proteins and their fractionation].
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Blood Proteins↗
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[Extraction of drugs in plasma exchange].
Plasma exchange has been proposed for treating diseases mediated by circulating immune complexes. Removal of drugs during plasma exchange is a complex function of pharmacokinetic characteristics and specifications of the plasma exchange procedure: the time of plasma exchange, the filtered volume of plasma, the number of procedure. The effect of plasma exchange on the kinetics of drugs can be evaluated by different parameters: amount eliminated, extracorporeal clearance, fractional drug removal, extracorporeal elimination rate constant. Knowledge of the impact of plasma on the elimination of drugs is essential to the design of the dosage regimen in patients treated with plasma exchange. The fraction of the estimated amount in body removed by plasma exchange is the best parameter to evaluate the effectiveness of the exchange procedure, but it is necessary to know the proportion of body pool of drug at the start of the plasma exchange. Drug recovery by each exchange may account for 0.5%-30% of the dose. Controlled studies are needed to quantify the effects of plasma exchange on drug therapy. Dosage adjustment is sometimes required.
Humans↗
Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.
BACKGROUND: Thrombotic thrombocytopenic purpura is an uncommon disease with a high mortality rate even with current treatment. The cause of the syndrome and its optimal treatment are unknown. Although both plasma exchange and plasma infusion have been useful treatments, it is not clear which is superior. In this report we describe a prospective randomized trial comparing plasma exchange with plasma infusion for the treatment of thrombotic thrombocytopenic purpura. METHODS: One hundred two patients with thrombotic thrombocytopenic purpura were randomly assigned to receive either plasma exchange or plasma infusion with fresh-frozen plasma on seven of the first nine days after entry into the trial. The total volume of plasma received by patients undergoing plasma exchange was three times that received by patients undergoing plasma infusion. All the patients also received aspirin and dipyridamole. The outcomes in the two groups were compared at the end of the first treatment cycle (day 9) and after six months. RESULTS: At the end of the first treatment cycle patients receiving plasma exchange had a higher rate of response as defined by an increase in the platelet count (24 of 51 patients) than those who received plasma infusion (13 of 51, P = 0.025). Of the 51 patients treated with plasma exchange, 2 died, whereas 8 of the 51 patients who received plasma infusion died (P = 0.035). After six months the outcome in the plasma-exchange group was still superior, with a response observed in 40 of 51 patients, whereas 25 of 51 patients in the plasma-infusion group responded (P = 0.002). Eleven patients in the plasma-exchange group died, as did 19 patients in the plasma-infusion group (P = 0.036). The overall mortality was 29 percent. CONCLUSIONS: Plasma exchange is more effective than plasma infusion in the treatment of thrombotic thrombocytopenic purpura.
Adult↗
Selective plasma component removal: alternatives to plasma exchange.
Plasma exchange, the unselective removal of all plasma constituents, has been applied, with varying degrees of success, to an increasing number of disorders. Because of the high cost of plasma exchange, largely the result of expensive homologous replacement solution, and other reasons, alternatives have been sought. Selective removal of plasma components permits the use of autologous plasma as replacement which is less costly, more physiologic, and in some cases, a more efficient alternative to plasma exchange. The selective removal of plasma components whose presence is associated with a disease process can be accomplished presently by physical or chemical means with either on-line of off-line systems. A state-of-the-art review of currently available alternatives to plasma exchange is described. This includes hemoperfusion and plasmaperfusion over affinity columns or filters with immobilized sorbents. On-line separation of macromolecules by membrane filtration and cryoprecipitation as well as off-line chemical precipitation and cryoprecipitation are also described. The potential and limitations of the techniques are emphasized.
Agglutinins↗
Efficacy of membrane filtration, influence on hemostasis, immunoglobulins and inflammation mediators during daily plasma exchanges.
Plasma exchange (PE) by membrane filtration was performed with the following hollow fibers: cellulose-diacetate (Plasmaflo 01, Plasmaflo 02, Asahi, Japan), polypropylene (Plasmaflux, Fresenius, FRG) and polymethylmethacrylate (Plasmax, Toray, Japan). The elimination-coefficient (EC) for certain plasma proteins was calculated. With all hollow fibers no correlation between the EC for about ten plasma proteins with a molecular weight of 54.000 dalton up to 2.400.000 dalton. The mean EC-values for the fibers studied were: 0.32 (Plasmaflo 01), 0.52 (Plasmaflo 02), 0.52 (Plasmaflux) and 0.58 (Plasmax). Membrane filtration performed with the single needle technique using either Plasmaflo 02 or Plasmaflux resulted in a significantly lower efficiency with mean EC-values of 0.33 and 0.32 respectively. After three or four days of PE treatment using three liters of 3% human albumin solution as replacement fluid several alterations in parameters of hemostasis were altered: Antithrombin III levels dropped to 35% of normal value after each plasma exchange but increased to normal range within 24 hours during the observed period of four consecutive PE, Fibrinogen concentration dropped permanently to a preexchange value of 40% of the initial concentration after three plasma exchanges. A 40-50% decrease was also observed for prothrombin, plasminogen and alpha-2-macroglobulin after plasma exchange. A decrease in the platelet count ranging from 5 to 25% after each plasma exchange was observed but returned to the initial level before the next treatment. The concentrations of IgG IgA and IgM decreased to less than 20% of preexchange values and C 3 and C 4 to 20-30: of preexchange values after three plasma exchanges.(ABSTRACT TRUNCATED AT 250 WORDS)
Filtration↗
Therapeutic plasmapheresis and plasma exchange.
Plasma exchange is a process in which large volumes of plasma, usually equivalent to one plasma volume, are exchanged with donor plasma or a plasma substitute. This permits the removal of antibody, immune complexes, inflammatory mediators, paraproteins, drugs, toxins, and other plasma constituents. Plasma exchange may also have an effect on the immune system by enhancing the function of the reticuloendothelial system, removing blocking antibody, increasing clearance of tumor cells, and making lymphocytes more vulnerable to immunosuppressive drugs. Over 100 diseases have been treated with plasma exchange with variable success. Results of controlled studies are less dramatic than those of earlier uncontrolled case reports. Reports of complications and even death have tempered initial enthusiasm. Now, over a decade since the initial promising reports began to appear in the literature, the role of plasma exchange remains undefined.
Amyotrophic Lateral Sclerosis↗
Phenytoin removal during plasma exchange.
Plasma exchange is currently being used to treat a variety of disorders including immune complex and hematologic disorders. It has been shown that the removal of plasma removes drugs bound to plasma proteins. This case documents the removal of phenytoin during plasma exchange therapy. Total and free phenytoin serum concentrations were obtained before and after each exchange. Aliquots were obtained from each pass, and total phenytoin concentrations were determined. The total phenytoin serum concentration increased during the first exchange, while the total concentration decreased as a result of the second exchange. It was determined that approximately 27.7 mg and 30.4 mg of phenytoin were removed by the first and second plasma exchanges, respectively.
Adolescent↗
Treatment of Guillain-Barré syndrome by plasma exchange.
Plasma exchange has been used for therapy in eight patients with the Guillain-Barré syndrome. All patients were severely ill. They became tetraplegic and showed cranial nerve involvement. Five patients received assisted respiration, but the others were also at risk of ventilatory insufficiency. Recovery was abrupt in all cases after the first plasma exchanges. Improvement was more marked when plasmapheresis was done on three successive days with plasma exchanges of 2.0-3.01 each in the initial progressive stage of the disease. A considerable advantage of this therapy is the avoidance of continued artificial respiration and nutrition, which both carry the risk of further complications.
Adult↗
Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma separation and cascade filtration in patients with immunocytoma of Waldenström's type.
The hyperviscosity syndrome is a common problem in patients suffering from IgM paraproteinemia. In this situation cytotoxic chemotherapy alone is insufficient and additional plasma therapy is required. Until recently, conventional plasma exchange was the only plasma therapy available. While this method has proven its efficacy, it eliminates proteins unselectively. Cascade filtration, on the other hand, has been established to remove proteins as a function of their size offering the prospect of a highly selective withdrawal of macromolecules. In the work presented, the efficacy of conventional plasma exchange and cascade filtration was evaluated performing both techniques at random in cases of hyperviscosity syndrome due to immunocytoma of Waldenström's type (n = 11/group). In these patients, conventional plasma exchange decreased plasma viscosity by 48%; cascade filtration was less effective (26%), correlating with a smaller decrease of IgM (conventional plasma exchange 42% vs cascade filtration 27%). The profile of other plasma proteins studied did not change significantly with either treatment. Furthermore, we observed no differences regarding serious side-effects. In conclusion, we could not demonstrate a superior effect of cascade filtration as compared to conventional plasma exchange in the treatment of hyperviscosity syndrome.
Aged↗
[Treatment of emergency situations in autoimmune diseases with plasma exchange].
Plasma exchange has been applied successfully to treat severely ill patients with autoimmune diseases in recent years. We report on 12 patients with systemic lupus erythematosus (SLE), myasthenia gravis (MG), and Goodpasturés syndrome (GS), that have been treated with membrane plasma separation. Two to three liters of plasma were exchanged per session. Three to nine treatments were done within 1--4 weeks. Human albumin solution was used for replacement of the discarded plasma. Improvement was seen in 3 out of 5 SLE patients, in all 5 myasthenic patients and in one of the two patients with GS. Plasma exchange in combination with immunosuppressive therapy is indicated in states of active autoimmune diseases, not controllable by routine immunosuppression. For long-term treatment, however, immunosuppressive medication should be used.
Adolescent↗
Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange.
Plasma exchange was undertaken in five patients with homozygous familial hypercholesterolaemia at intervals of two weeks for a mean of 8.4 years. These patients had survived an average of 5.5 years longer than their five respective homozygous siblings (p = 0.3), each of whom must have had a matching genetic defect but who died untreated. The 37% decrease in peak serum cholesterol concentrations maintained by plasma exchange presumably reduced progression of atherosclerosis in the treated patients and thus lessened their risk of premature death.
Adolescent↗
[Which patients should be treated with plasma exchange? Indications for plasma exchange therapy].
What is the current opinion on therapeutic plasma exchange, after 20 years of clinical use for numerous patients and disease states? Principles of rational therapy have broken through into the field of therapeutic plasmapheresis during the last decade. Efficacy proven by controlled clinical trials is the prerequisite for determining indications. Superiority of plasma exchange over other therapeutic modalities has been established for only a limited number of rare diseases. Plasma exchange treatment is still actual for plasmatic hyperviscosity syndromes in the course of haematological and rheumatological diseases. Indications for therapeutic plasma exchange in nephrology are narrowed to some forms of Goodpasture's syndrome, rapidly progressive glomerulonephritis with antineutrophil cytoplasmic antibodies and renal insufficiency, and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome. Plasma exchange therapy is indicated for severe forms of Guillain-Barré syndrome and myasthenia gravis. Therapeutic benefit of plasma exchange was not found by controlled clinical trials in patients with rheumatoid arthritis, systemic lupus erythematosus, polymyositis, dermatomyositis, multiple sclerosis and rejection of kidney allotransplant.
Humans↗
Assessment of the combined effect of plasma exchange and plasma perfusion on patients with severe hepatitis awaiting orthotopic liver transplantation.
To determine if plasma exchange combined with plasma perfusion is a reliable and effective temporary liver support treatment for patients on the waiting list for OLT, we tested this method in 5 patients with end-stage and 3 patients with middle-stage severe hepatitis. Four patients were successfully controlled until a donor liver was available 4 to 13 days later. In contrast, the remaining 4 patients were not adequately controlled by this treatment and experienced aggravated disease progression, dying 3 to 8 days after treatment while still awaiting OLT. Of those 4 patients who received OLT, 2 patients died from multi-organ failure caused by hepatic failure, while the other 2 survived. These findings show that plasma exchange combined with plasma perfusion provides temporary support for some patients on the waiting list for OLT. The ability of patients to successfully bridge to OLT is closely associated with the degree of liver failure, complications, multi-organ failure, and the length of the waiting period for a donor liver.
Adult↗
Soluble adhesion molecules and cytokines in patients with myasthenia gravis treated by plasma exchange.
Plasma exchange (PE) is an effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except for acetylcholine receptor antibodies (AChRAbs), some other inflammatory mediators possibly activated in MG may also be removed during PE. Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL-6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 MG patients assigned to treatment with PE. On the basis of the serum levels of AChRAb the patients were subdivided into 2 groups (8 patients with low AChRAb, 12 patients with high AChRAb). Soluble adhesion molecules and cytokines were measured before the first and last PE, at the end of the first PE and in the samples of plasma filtrate obtained during the first PE. Before the first PE patients with MG had higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both after the first PE and during the course of PE, a substantial decrease in serum levels of AChRAb, sICAM-1 and sVCAM-1 was recorded. However, serum levels of sIL-2R and sTNF-R II were not significantly influenced by either a single treatment or during the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrates too. Patients with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than patients with low AChRAb. Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in patients with MG suggest some systemic activation of the immune response which is more pronounced in patients with high circulating AChRAb. PE led to the decrease in serum AChRAb and soluble adhesion molecules due to their effective filtration but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with the synthetic membrane.
Adult↗
Function of circulating antibody to acetylcholine receptor in myasthenia gravis: investigation by plasma exchange.
Plasma exchange has been used to investigate the function fo anti-acetylcholine receptor (anti-AChR) antibody in seven patients with acquired myasthenia gravis (MG) who had elevated antibody titers and in one patient with congenital MG who had normal titers. There was an inverse association between clinical indices of muscle strength and anti-AChR titers, with a minimum time lag of 2 days for the clinical response. The inverse association of the clinical state with anti-AChR antibody titers was closer than that with total immunoglobulin G or other immunoglobulins, and is consistent with the view that the anti-AChR antibody is the principal factor interfering with neuromuscular transmission in acquired MG.
Adult↗
[Immunoglobulins or plasma exchange? Synchronization of plasma exchange and intravenous polyvalent immunoglobulins. A consecutive study of 11 patients].
Synchronization is defined as a prescription sequence aimed at obtaining synergic response or potentialization. THEORETICAL BASIS--The concept of synchronization is based on clinical and biological observations such as similar indications and transient effectiveness. Certain mechanisms of action such as reduction of pathological autoantibodies and accelerated elimination of immune complexes are common to both methods. Inversely, long-term effects differ. Plasma exchange cannot control the synthesis (or could aggravate) of autoantibodies while gammaglobulins have a suppressor effect on autoreactive clones. The aim is to obtain a summation effect by eliminating immediately cytotoxic factors. The potentializing effect of gammaglobulin anti-idiotypes on the modification of the immunologic repertory is favoured by prior reduction in the level of circulating pathogenic antibodies. RESULTS--It is difficult to evaluate the efficacy of this therapeutic association. Only a few trials have been conducted in refractory autoimmune thrombopenic purpura (n = 8), in intra-uterine Rhesus disease (n = 3), and HIV associated pathologies. We report our experience in 11 patients in a situation of therapeutic failure including three cases of renal transplantation, two cases each of chronic polyradiculoneuritis and neurological paraneoplastic syndromes, and one case each of Wegener's syndrome, polymyositis, sclerokeratitis, and antiphospholipid antibodies during pregnancy. Immunoglobulins were injected at an initial dose of 2 g/kg following at least 3 plasma exchanges. Consolidation cures were then administered every 3 weeks at a dose of 1 g/kg. Two major complications occurred and required interruption of the treatment: acute regressive oligo-anuric renal failure (Wegener) and exacerbation of sclerokeratitis inflammatory lesions. The disease process was controlled in 7 patients. CONCLUSIONS--Despite these promising preliminary results, the proposed combination therapy is not devoid of complications and its cost is high (cost of PE for 500 mg/kg Ig is about 5,000 FF). The next step should be the study of experimental models and prospective trials on pathologies with well characterized immunological features.
Adult↗
Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura.
Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P <.00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% ( approximately 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P <.02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.
ADAM Proteins↗
Time course of improved neuromuscular function following plasma exchange alone and plasma exchange with prednisone/azathioprine in myasthenia gravis.
Ten patients with myasthenia gravis (MG) were treated with weekly plasma exchange (PE) in combination with prednisone and azathioprine; 4 of the patients were treated with 3-6 PE alone, before instituting prednisone/azathioprine. Four clinico-physiological parameters of neuromuscular function as well as the anti-acetylcholine receptor antibody (anti-AChRAb) titers were measured 1-3 times per week. Evidence of improved neuromuscular function (NMF) was based on: (1) reduced % decrement of the maximum muscle compound potential following 2/s supramaximal nerve stimulation; (2) increased maximum force; (3) increased outstretched arm time, and (4) increased vital capacity. An early improvement in NMF occurred within the first 2 weeks (sometimes as early as 1-2 days), which was quantitatively comparable in patients treated with PE alone and PE plus prednisone/azathioprine. This early improvement reached a plateau, and was subsequently maintained for 3-4 weeks, followed by a later substantial improvement after 8-12 weeks of combined PE plus prednisone/azathioprine.
Adult↗