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PubMed1999

Optimal volume of processed plasma and total number of selective plasmapheresis sessions in the treatment of patients with severe generalized myasthenia gravis.

The selection of the technical parameters of plasmapheresis in the treatment of patients with MG varies widely due to the lack of sufficient data from controlled studies to standardize the plasmapheresis procedure. Eight myasthenia gravis (MG) patients (Osserman IIb and III) received either immunoadsorption plasmapheresis (IA) with a IM-TR 350 (Asahi Medical Co., Tokyo, Japan) or double filtration plasmapheresis (DF) with a Cascadeflo AC-1770, with four in each group. A Plasmaflo AP 05 W (Asahi Medical Co., Tokyo, Japan) was used as the plasma separator in both groups. Each course of treatment consisted of five sessions of aphereses on alternate days. Plasma was sampled before and after passing through the column. Samples of plasma were analyzed for acetylcholine receptor antibody (AchRAb) at the start of plasmapheresis and sequentially after every 0.5 L of plasma treated. The IA method cleared significantly more AchRAb during the initial treatment of 1. 5 L of plasma than the DF method, especially in the initial 1 L (P < 0.01). The column saturated after treatment of 1.5 to 2 L of plasma. It is known that over-saturation of column may release the already adsorbed/filtrated antibodies. Longitudinal analysis on the serological changes during the five sessions revealed that the clearance obtained using the IA method was significantly higher and more sustained after the first session of treatment compared to the DF method (P < 0.05). The titers of AchRAb were also noted to rise after the fourth session. These results suggest that 2 L of processed volume is optimal in terms of the functional capacity of a plasmapheresis column in either IA or DF methods, and that a total of four sessions of treatment in one course may provide optimal elimination of AchRAb.

Adult↗
PubMed1998

Severe infections in plasmapheresis-treated systemic lupus erythematosus.

OBJECTIVE: To assess the risk of infection in patients with systemic lupus erythematosus (SLE) treated with plasmapheresis in addition to intravenous (I.V.) pulse cyclophosphamide (CYC). METHODS: We searched the records of all our SLE patients for those who had undergone plasmapheresis plus I.V. CYC treatment (n = 9). Consecutive patients with similarly high SLE activity who underwent I.V. CYC therapy but not plasmapheresis were included as controls (n = 12). We evaluated both groups for severe infections, outcome, and confounding clinical variables. RESULTS: Seven of 9 plasmapheresis-treated patients had serious bacterial or viral infections, including 3 cases of cytomegalovirus infections. Among the 12 patients treated with I.V. CYC alone, only 2 had severe infections (P < 0.01). Three patients in the plasmapheresis group and none in the control group died of infections. Treatment efficacy, however, was similar for both groups. CONCLUSION: Among SLE patients treated with plasmapheresis and I.V. CYC, life-threatening bacterial and viral infections and mortality occur more frequently than among patients with similarly active SLE treated with I.V. CYC alone.

Adult↗
PubMed1981

Plasmapheresis and immunosuppressive drug therapy in scleroderma.

In an uncontrolled clinical trial, plasmapheresis combined with prednisone and cyclophosphamide therapy produced clinical improvement in 14 of 15 scleroderma patients with varying degrees of skin and internal organ involvement. All improved patients showed a gradual loosening of hide-bound skin, relaxation of contractures, and healing cutaneous ulcers, when present. Severe gastrointestinal symptoms were ameliorated in 4 patients, severe polymyositis was largely reversed in 2 patients, and pulmonary and cardiac function was improved in others. After initial improvement, however, 2 patients died during the period of study and another withdrew unimproved. Antinuclear antibody (ANA) titers declined relatively more than total IgG levels with plasmapheresis in 6 of the 9 patients who had elevated titers. Increased levels of endothelial cell cytotoxic activity found in 11 of the 15 patients were significantly reduced by plasmapheresis. Elevated levels of circulating immune complexes were found in only 4 of the 15 patients. Skin biopsies from adjacent sites taken before and after plasmapheresis in 10 patients all showed less swollen dermal collagen with increased ground substance between collagen bundles in the second biopsy. Although the effects of plasmapheresis cannot be dissociated from those of the immunosuppressive drug therapy, our results suggest that plasmapheresis combined with immunosuppressive drug therapy may find a place in the management of patients with moderate to severe scleroderma. This study implicates circulating factors in the pathogenesis of the disease.

Adult↗
PubMed1990

Antibody response to pneumococcal polysaccharide vaccine in myasthenia gravis: effect of therapeutic plasmapheresis.

The removal of specific antibody in experimental animals has been reported to result in a subsequent increase in antibody to levels equal to (rebound) or exceeding those existing prior to removal (overshoot). Anecdotal reports suggest that rebound antibody synthesis after plasmapheresis may occur in humans with autoimmune disorders. We measured the antibody response to 12 pneumococcal polysaccharide antigens in patients with myasthenia gravis (MG) receiving a variety of therapies in order to determine whether the T-cell-independent IgG response to these antigens was augmented by plasmapheresis. MG patients receiving no immunotherapy or receiving prednisone had pre- and post-immunization titers similar to those of control patients. MG patients receiving prednisone and chronic plasmapheresis had higher pre-immunization titers than did other patient groups and had significantly higher post-immunization titers against multiple pneumococcal serogroups. Aggregate post-immunization geometric mean titers were more than three-fold higher in the plasmapheresis group as compared with other MG treatment groups. Enhancement of antibody response by plasmapheresis was abolished by the concomitant administration of azathioprine. Antibody rebound and overshoot after antibody removal may have important implications for the therapy of immune disorders by plasmapheresis.

Adult↗
PubMed1990

Therapeutic plasmapheresis and protein A immunoadsorption in malignancy: a brief review.

Plasmapheresis is being used with considerable frequency in the management of malignant and non-malignant disorders. More recently, staphylococcal Protein A immunoadsorption has been employed in similar clinical situations. In patients with malignancy, plasmapheresis has been shown to produce alterations in plasma proteins, decrease circulating immune complexes, remove "specific" and "non-specific" blocking factors, change immune reactivity, and affect monocyte function. Partial responses have been reported in a small number of patients with carcinoma of lung, colon, and breast following plasmapheresis. In addition, there are reports of favorable responses in patients with melanoma, head and neck tumors, lymphomas, leukemias, and Kaposi's sarcoma in acquired immune deficiency. All these responses were partial and brief, and the treatment did not alter the course of the disease. Plasmapheresis has been useful in the management of hyperviscosity and occasionally of paraneoplastic syndromes. It may also have a role in the treatment of thrombotic thrombocytopenic purpura associated with mitomycin-C therapy. Protein A immunoadsorption, by which circulating immune complexes are selectively removed, can activate the complement system, increase blastogenic responses, and increase the natural killer cell activity. It has been shown to produce partial responses in breast and colon cancer, as well as Kaposi's sarcoma in acquired immune deficiency. It may have a useful role to play in the management of mitomycin-C-associated thrombotic thrombocytopenic purpura. Both plasmapheresis and Protein A immunoadsorption should be considered investigational interventions at this time. Toxicity of plasmapheresis, though uncommon, can be serious and may rarely be fatal. Toxicity of Protein A immunoadsorption is mild, consisting mainly of influenza-like symptoms and rash.

Combined Modality Therapy↗
PubMed1994

Prolonged circulation of activated platelets following plasmapheresis.

The extent and duration of in vivo platelet activation were determined in 12 volunteer donors undergoing automated plasmapheresis. Expression of P-selectin, activated GpIIb/IIIa, and platelet microparticle formation were measured by flow cytometry on peripheral blood samples obtained immediately before and after plasmapheresis and at 24 hour intervals thereafter for up to 3 days. Although no adverse effects were noted in any donor, immediately after apheresis 3-87% of circulating platelets expressed P-selectin; by 48 hours, 0.5-50% expressed P-selectin; and by 72 hours, all donors studied had fewer than 5% P-selectin expression on circulating platelets. Results were similar for the expression of the activated conformation of GpIIb/IIIa. There was a positive correlation with in vitro P-selectin expression in response to ADP in the pre-apheresis sample and the number of platelet microparticles detected in the donor following plasmapheresis. In addition, the percent expression of P-selectin and activated GpIIb/IIIa in response to ADP was reproducible in each individual studied on five separate occasions (CV < or = 8%). Platelets activated during plasmapheresis using an automated device may circulate for at least 48 hours, and pre-plasmapheresis response of platelets to the agonist ADP correlated with platelet microparticle formation post-plasmapheresis.

Adenosine Diphosphate↗
PubMedDate not supplied

Effect of plasmapheresis and steroid treatment on thyrotropin binding inhibitory immunoglobulins in a patient with exophthalmos and a patient with pretibial myxedema.

The effect of prednisone treatment and plasmapheresis was studied in two patients with Graves' disease complicated by severe exophthalmos and/or pretibial myxedema. Titers of Thyrotropin Binding Inhibitory Immunoglobulins (TBII), Long Acting Thyroid Stimulator (LATS), antithyroid antibodies, and serum gammaglobulin concentrations, as well as clinical changes in exophthalmos and pretibial myxedema, were observed during the course of treatment. Steroid treatment lowered all of the abnormal antibody titers. Plasmapheresis did not change the TBII activity when determined using a fixed amount of immunoglobulin G fraction. However, serum gammaglobulin concentration was reduced by plasmapheresis, and therefore, total TBII activity in a unit of serum was reduced. Plasmapheresis also partially and temporarily resolved the pretibial myxedema, whereas no significant change in exophthalmos was observed. These results suggest that both steroid and plasmapheresis treatment are useful for lowering abnormal antibody titers in sera of patients with Graves' disease, and that plasmapheresis can be of some value in the treatment of pretibial myxedema.

Adult↗
PubMed2001

Long-term plasmapheresis and protein A column treatment of recurrent FSGS.

Transient or intermittent plasmapheresis with concurrent immunosuppressive therapy is thought to be beneficial in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the early post-transplant period. The results of long-term (6-year) plasmapheresis therapy, in a 9-year-old female with an immediate recurrence of FSGS [urinary protein/urinary creatinine (UP/UC)=17.7] after cadaveric renal transplant, are presented. A 4-week plasmapheresis course induced a decline in the proteinuria, but a relapse occurred after cessation of plasmapheresis. Addition of protein A column therapy led to a further decrease in the proteinuria, to a non-nephrotic range. Long-term control of the nephrotic syndrome was established using a chronic treatment regimen consisting of a single-volume plasmapheresis, followed by a protein A column treatment, performed on sequential days every 3-4 weeks. Mean UP/UC values decreased to 1.15+/-0.9. A course of cyclophosphamide was successfully used to control a worsening of proteinuria 4 years post transplant. Although sequential renal biopsies demonstrated progressive glomerular sclerosis, the patient's mean calculated creatinine clearance only modestly declined from 78.3 ml/min per 1.73 m2, at the time of transplantation, to 62.7 ml/min per 1.73 m2, 6 years later. This patient demonstrated dependence on plasmapheresis/protein A column therapy to maintain a clinical remission of her FSGS recurrence. While long-term plasmapheresis and protein A column therapy in combination with immunosuppressive therapy reversed the effects of uncontrolled nephrosis and possibly facilitated long-term renal allograft survival, the glomerular sclerosis continued to progress.

Child↗
PubMed1990

RETRACTED: Acute preoperative plasmapheresis and established blood conservation techniques.

Plasmapheresis performed weeks before an operation producing autologous plasma has proved to be of benefit in elective operations. First experiences in acute plasmapheresis, which is performed immediately before the operation, have been reported recently. When acute plasmapheresis is used in cardiac operations, however, it must be viewed in connection with other techniques for reducing blood consumption such as the Cell Saver (CS) and ultrafiltration devices. In 60 patients undergoing elective aortocoronary bypass grafting, acute plasmapheresis was performed, producing either platelet-poor plasma or platelet-rich plasma, in combination with either the Cell Saver or hemofiltration. Fluid balance during cardiopulmonary bypass was significantly lower in the hemofiltration patients. Postoperatively, none of these patients received donor blood, whereas 4 patients of the Cell-Saver groups needed packed red blood cells. AT-III, fibrinogen, the number of platelets, albumin, total protein, and colloid osmotic pressure were less compromised when hemofiltration was used in combination with acute plasmapheresis in contrast to combination with the Cell-Saver technique. Plasma hemoglobin was without differences during the investigation period, and polymorphonuclear elastase was less increased when platelet-rich plasma was produced preoperatively. On the first postoperative day, most of the differences between the groups had already disappeared. We conclude that when acute plasmapheresis is used in cardiac operations, discarding of plasma by the Cell Saver should be avoided and ultrafiltration devices should replace centrifugation techniques for blood conservation.

Blood Coagulation Factors↗
PubMedDate not supplied

Plasmapheresis in the treatment of the Guillain-Barré syndrome in childhood.

Four patients (two boys and two girls, 6 to 13 years of age) with the Guillain-Barré syndrome (GBS) exhibiting such pronounced symptoms as dyspnea and dysphagia were treated with plasmapheresis using an intermittent flow system or double filtration plasmapheresis. The duration of the disease before plasmapheresis varied between 4 and 11 days. Three of the four patients experienced marked improvement during the course of plasmapheresis, but one patient had only partial improvement. No serious complications occurred. Good clinical and electrophysiologic recovery enjoyed by most patients treated with plasmapheresis appears to confirm the efficacy of plasmapheresis in children with severe GBS.

Adolescent↗
PubMedDate not supplied

Value of plasmapheresis in hepatic encephalopathy.

Plasmapheresis is used for treating the complications of liver failure. We performed plasmapheresis on 6 children with hepatic encephalopathy resulting from acute hepatic failure and prospectively assessed its effects on neurologic and electrophysiologic (electroencephalography and evoked potentials) function. Clinical improvement was observed in 3 of 6 patients; changes in the serum ammonia value or the results of initial electrophysiologic tests did not predict the patient response. Two patients underwent transplantation after neurologic improvement was produced by plasmapheresis; however, despite plasmapheresis, 4 patients progressed to brain death. Our data demonstrate that plasmapheresis may transiently improve the encephalopathy of acute hepatic failure but is not curative alone. Therefore, plasmapheresis may be a useful adjunct in the treatment of liver failure, potentially improving the pretransplantation status of the patient.

Brain Stem↗
PubMedDate not supplied

Plasmapheresis with acute inflammatory polyneuropathy.

Eleven children with acute inflammatory polyneuropathy were treated with a short course of intensive plasmapheresis. The 5 males and 6 females ranged in aged from 19 months to 16 years (mean: 7.8 years). The interval from disease onset to the initiation of plasmapheresis therapy was less than 7 days in 5 patients and less than 2 weeks in the others. At the time of the first plasmapheresis, 3 patients were on respirators (Grade 5 on the Guillain-Barré syndrome scale 0-6); 7 were bedridden (Grade 4); and 1 required assisted ambulation (Grade 3). One week after the last plasmapheresis, all but 1 patient had improved by 1 or more grades on the Guillain-Barré syndrome scale. At subsequent examination 6 months later, all patients were ambulatory and 9 of 11 had no significant neurologic findings. Electrophysiologic studies performed shortly before treatment initiation revealed predominant demyelinating neuropathy in 9 and axonal changes in 2. During the 76 plasmapheresis procedures, no severe complications were encountered. Although the number of patients treated is small, the clinical response observed would indicate plasmapheresis to be a safe and effective therapy in children with acute inflammatory polyneuropathy.

Adolescent↗
PubMed2005

Capillary electrophoresis for monitoring the effects of plasmapheresis: a feasibility study.

Plasmapheresis is an established method to treat patients with large monoclonal gammopathies (M-components) that increases the blood viscosity. During plasmapheresis the patient plasma is substituted with a mixture of saline, albumin and normal plasma. The treatment results in a reduction of the M-component in the circulation. Plasmapheresis causes changes in several proteins, which makes monitoring by nephelometric or turbidimetric analysis of specific proteins less suitable. Quantification of paraproteins by nephelometric assays are also known to be associated with technical problems. An alternative could be agarose gel electrophoresis but this method is too slow to permit monitoring during the plasmapheresis. Capillary electrophoresis of plasma proteins can be performed in less than 10 min. We have used the CAPILLARYS capillary electrophoresis system (Sebia, Paris, France) to monitor the effect of plasmapheresis treatment on 22 occasions. The mean reduction in M-component size was 51%, range 33-61%. Capillary electrophoresis is a rapid and inexpensive method that could be used to monitor the effect of plasmapheresis during the actual treatment.

Blood Protein Electrophoresis↗
PubMed2005

The effects of automated plasmapheresis on clinical, haematological, biochemical and coagulation variables in horses.

The goal of this study was to determine the effects of plasmapheresis on the behaviour, general condition, haematological, biochemical and coagulation variables of donor horses for 32 days following the procedure. Twenty millilitres of plasma/kg body weight were collected via plasmapheresis in six clinically healthy horses. The general behaviour and condition of the horses was not affected by the procedure. During plasmapheresis, there was a mild increase in the haematocrit, haemoglobin concentration and total erythrocyte and leucocyte counts (P < 0.01). The mean concentrations of total protein and albumin decreased significantly (P < 0.01) and total protein did not normalise for about three weeks. Several other biochemical variables also decreased significantly during plasmapheresis, but mostly remained within reference ranges. After plasmapheresis, the mean value of the activated partial thromboplastin time and the thrombin time were mildly but significantly increased (P < 0.01), and the mean activities of factor V, factor VIII and antithrombin decreased significantly (P < 0.01), although all coagulation values remained within reference ranges. Our results indicate that, in horses, the collection of 20 mL of plasma/kg body weight via plasmapheresis results in mild changes in several haematological, biochemical and coagulation variables, although these were of no clinical relevance for the donors.

Analysis of Variance↗
PubMed1998

Plasmapheresis in treatment of acute oligoanuria in crescentic glomerulonephritis.

Plasmapheresis therapy can provide an approach in the treatment of crescentic glomerulonephritis by mechanically removing nephritogenic factors from the circulation, both antiglomerular basement membrane antibodies and circulating immune complexes as well as antineutrophil cytoplasmic antibodies (ANCAs). We present our experience with plasmapheresis treatment in patients with acute oligoanuria caused by crescentic glomerulonephritis. We used membrane plasmapheresis to treat 11 patients with crescentic glomerulonephritis with more than 80% crescent formation on biopsy and with acute onset of the disease and acute oligoanuria. The immune complex form of the disease was documented in 7, the antiglomerular basement membrane antibodies mediated (anti-GBM) form in 2, the ANCA-associated form in 1 case, and the recurrent anti-GBM form in 1 patient. Plasmapheresis was performed 2-3 times weekly using Bellco BL 500 and Gambro 2000 PF plasma filters. The total number of plasma exchanges (2,000-2,200 ml each) for each patient was 5-9. The treatment was associated with steroids and cyclophosphamide. The improvement of renal function with the start of diuresis and significant decrease of creatinine from the range of 786-1,301 microM at the start of the treatment was noted in 5 of the 11 patients. The duration of remission without hemodialysis was 6-12 months. Treatment with plasmapheresis in cases with recurrent anuria was without benefit. We can conclude that plasmapheresis can delay end-stage renal failure in cases with acute onset of crescentic glomerulonephritis.

Acute Disease↗
PubMed1999

Plasmapheresis and paraproteinemia: cryoprotein-induced diseases, monoclonal gammopathy, Waldenström's macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis.

Therapeutic plasmapheresis has been in widespread use as either a primary or adjunctive therapy in the United States since the 1960s. There are several types of plasmapheresis procedures used to treat various diseases. Plasma exchange with a centrifugal plasma separator using replacement fluid such as human albumin solution is the most widely used method in the United States. Other forms of plasmapheresis include membrane plasma separation, membrane fractionation, cryofiltration apheresis, immunoadsorption, and chemical affinity column pheresis. Therapeutic plasmapheresis has been used for the treatment of paraproteinemia to remove harmful paraproteins. Paraproteinemia is a disease classification in which abnormal or large amounts of plasma proteins such as cryoproteins or immunoglobulins are produced. In most cases, plasmapheresis is used in combination with corticosteroids and immunosuppressive drugs to prevent production of abnormal proteins or to treat the underlying disease. Cryoprotein-induced diseases, which include cryoglobulinemia, cryofibrinogenemia, and cold IgM antibody agglutinin with cryoglobulin properties, are a subclass of paraproteinemia. Other categories of paraproteinemia include monoclonal gammopathy, Waldenström's macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis. Some of these diseases may be interrelated, and they may be associated with one another. In this review paper, we discuss the role of plasmapheresis in the specific classes of paraproteinemia in the United States, including our own experience.

Amyloidosis↗
PubMedDate not supplied

Short-term and long-term effects of plasmapheresis on serum proteins and immunoglobulins.

In order to evaluate the short-term and long-term effects of plasmaapheresis on serum proteins and immunoglobulins, the levels of alpha1, alpha2, beta, and gamma globulins, and IgG, IgA, and IgM were measured and statistically evaluated in 41 active plasmapheresis donors donating 500 to 1,000 ml of plasma weekly for up to three years. During the initial four months of plasmapheresis, the percentage of alpha1 and alpha2 globulins manifested a statistically significant rise and the IgG, IgA, and IgM concentrations declined. By the end of ten months, only the IgM continued to be depressed. Although the concentration of IgM continued to show a statistically significant decline for three years, it remained well within the normal range of values for our laboratory. Although no statistically significant difference existed between the baseline value of albumin and the level reached at the end of the third year, a gradual rise was followed by a decline in this interval. Most of the statistically significant alterations of serum protein and immunoglobulins occurring in plasmapheresis donors are seen in the initial six months of plasmapheresis. A falling serum protein in this time period is most likely an indication of declining immunoglobulins. It is feasible and appropriate to measure the donor's total serum protein at the time of each plasmapheresis. Any untoward reduction in this value necessitates quantification of the serum immunoglobulins. Routine measurement of the immunoglobulins in the face of normal total serum protein can be performed on a less frequent basis as is presently recommended by accrediting agencies, although this study should be performed more often during the first six months of a serial plasmapheresis program.

Alpha-Globulins↗
PubMed2003

Extracorporeal blood volume of donors during automated intermittent-flow plasmapheresis and its relevance to the prevention of circulatory reactions.

BACKGROUND: Intermittent-flow plasmapheresis often involves a large extracorporeal blood volume of the donor during the procedure with the concomitant risk of circulatory reactions. Guidelines governing donor recruitment often apply an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures. No data demonstrating the suitability of this approach exist. STUDY DESIGN AND METHODS: The blood volumes of 1204 plasmapheresis donors were calculated with different formulae that utilized either body weight or body surface area. Extracorporeal blood volumes of these donors were determined for a commonly used intermittent-flow plasmapheresis machine known to result in a large extracorporeal blood volume. A validated model was employed that calculated the fluid volume shifts occurring during the procedure. The records of all plasmapheresis procedures of these donors were retrospectively reviewed for circulatory reactions. RESULTS: The median extracorporeal volumes ranged from 14 to 17 percent of the blood volume at a donor Hct level of 0.40 to 0.48 L per L for men and from 17 to 20 percent at a Hct level of 0.36 to 0.44 L per L for women. In more than 60 percent of male and more than 90 percent of female donors, extracorporeal volumes exceeded 15 percent of the blood volume during plasmapheresis. In this subgroup, 65 percent of male and 75 percent of female donors never presented with any signs of circulatory reactions. CONCLUSION: Application of an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures is expected to lead to an unjustified deferral rate in plasmapheresis donors.

Automation↗