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Complete remission of post-transplant FSGS recurrence by long-term plasmapheresis.

Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though a putative circulating permeability factor or loss of inhibitory substances is being discussed. Different therapeutic approaches have been used. We report on a 10-year-old Arabian boy with a recurrence of FSGS immediately after transplantation. In addition to intensifying immunosuppressive therapy with high-dose cyclosporin A and cyclophosphamide, plasmapheresis was initiated and remission was achieved after 8 months. Three weeks after cessation of plasmapheresis a relapse occurred. Plasmapheresis was resumed and remission was achieved again after four additional sessions. The interval between plasmapheresis treatments was then gradually increased and fourteen months after transplantation plasmapheresis was stopped again. Since then (1.5 years after cessation of treatment) the patient has been in complete remission without any further episode of proteinuria. In conclusion, complete and sustained remission with stable renal function was achieved in our patient by long-term plasmapheresis in combination with intensified immunosuppression. Therefore, continuation of plasmapheresis treatment should be considered even in the situation of initial non-response.

Administration, Oral↗

Plasmapheresis in a very young infant with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, the pathogenesis of which is unclear. Plasma transfusions and plasmapheresis are widely used modes of therapy for adults with this life-threatening syndrome. There is very limited experience in using plasmapheresis therapy in children and infants with atypical HUS. Plasmapheresis, which is considered a relatively safe procedure in adults and older children, may be hazardous in neonates and very young infants and can result in severe complications. We report a 2-month-old infant with idiopathic atypical HUS, who was successfully treated with a 1-month course of plasmapheresis during the acute phase of the disease. Appropriate preparations as well as several adjustments were made in order to meet the special needs of this very young infant who, to the best of our knowledge, is the youngest reported patient with atypical HUS to undergo plasmapheresis. Plasmapheresis therapy of the infant was not associated with any complications of the procedure and resulted in marked clinical improvement. We conclude that plasmapheresis in neonates and in very small infants is technically feasible, can be performed without major complications, and may be of benefit in individual cases.

Feasibility Studies↗

Guillain-Barré syndrome in childhood: natural course and efficacy of plasmapheresis.

Eight children with Guillain-Barré syndrome were treated with plasmapheresis. Retrospective comparisons were made with 11 historic control patients. Eight children required mechanical ventilation, 4 of whom were in the plasmapheresis group. One week after the last plasmapheresis treatment, patients receiving plasmapheresis within 7 days of symptom onset had improved by one Guillain-Barré syndrome score. Discharge Guillain-Barré syndrome scores were significantly lower for those receiving plasmapheresis (P < .05). Patients in the plasmapheresis group had a decrease in the number of days of mechanical ventilation, time until motor recovery, and overall cost. Our results are consistent with published literature and indicate that plasmapheresis for childhood Guillain-Barré syndrome is a safe and effective treatment to shorten the time to recovery.

Adolescent↗

Effect of plasmapheresis for acute humoral rejection after heart transplantation.

OBJECTIVE: The objective of this study was to report our experience of treating acute humoral rejection with plasmapheresis in heart transplant (HT) recipients. PATIENTS AND METHODS: From May 1996 to December 2005, 238 HTs were performed using therapy with cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil, and prednisolone as well as induction treatment with rabbit anti-human thymocyte globulin. Endomyocardial biopsy for rejection surveillance was performed weekly for the first month, monthly for 3 months, yearly after the first year, and whenever rejection was suspected. Immunofluorescence studies with IgG, IgM, C3, C4, C1q, and HLA-DR were performed routinely on the first month biopsy. After a 2-year trial, immunofluorescence studies were not performed routinely, because no significant findings were observed; thus they were performed only when clinical deterioration, unstable hemodynamic status, or suspicion of rejection occurred on routine echocardiographic examinations. Plasmapheresis with fresh frozen plasma exchanging twice the blood volume of the patients was performed for 5 days. Rescue immunosuppression with methylprednisolone (1 g/d) was delivered for 3 days and the immunosuppressants changed, but no intravenous immunoglobulin was prescribed. RESULTS: Twelve patients suffered biopsy-proven acute humoral rejection at 3 days to 32 months after HT (mean, 9.4 months). Immunofluorescence studies showed positive HLA-DR in 7 patients; IgG in 4 patients; IgM in 1 patient; C3 in 4 patients; C4 in 1 patient; and C1q in 1 patient. One patient who was 3 months after HT showed only C1q positive but was treated with extracorporeal membrane oxygenation and intra-aortic balloon pumping support and died 1-month after plasmapheresis. Another patient who deteriorated on the 3rd postoperative day and died 3 days after plasmapheresis was considered to have vascular rejection by interstitial edema, vacuolated endothelial cells and no pathognomonic clinical features, although there was no positive immunofluorescence result. All other subjects were discharged from the hospital, although 3 required mechanical support during plasmapheresis. Hypotension with hypocalcemia was frequently noted during plasmapheresis. The 1-year survival rate was 75% +/- 11%, and 5-year survival rate, 51% +/- 15%. CONCLUSION: Plasmapheresis with concurrent rescue immunosuppression was an effective treatment for acute humoral rejection in HT even with unstable hemodynamics.

ABO Blood-Group System↗

Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis.

To test the hypothesis that a circulating mediator is associated with recurrent idiopathic focal glomerulosclerosis (FGS), we studied the effect of plasmapheresis on reducing proteinuria in patients with the disease. An in vitro assay measured the capacity of sera before and after plasmapheresis to cause increased albumin permeability (P(albumin)++) in isolated rat glomeruli. Nine patients (five males aged 2 to 66 years) who underwent plasmapheresis for recurrent FGS were identified. Study variables included age, sex, time from diagnosis of recurrence to first pheresis, glomerular hyalinosis, complications, outcome, and proteinuria before and after plasmapheresis. Rat glomeruli were isolated in medium containing 4 g/dL bovine serum albumin, and P(albumin) was determined from the change in glomerular volume in response to an albumin gradient after incubation of the glomeruli in a 1:50 dilution of patient serum. Plasmapheresis reduced proteinuria from a mean of 12 +/- 7.46 g/24 hr to 5.1 +/- 7.39 g/24 hr (P = 0.03). Six patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had lasting remissions. Preplasmapheresis biopsies in the patients who did not achieve remissions showed both epithelial foot process effacement and glomerular sclerosis. Serum samples were available from four patients for albumin testing in vitro. P(albumin)++ was reduced from a mean of 0.76 +/- 0.17 before pheresis to 0.18 +/- 0.31 after (P = 0.07). Therefore, the mechanism by which plasmapheresis reduces proteinuria in patients with recurrent FGS involves the decreased capacity of sera from these patients to injure the glomerular permeability barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Automated plasmapheresis compared with other plasma collection methods in the horse.

The purpose of this study was to evaluate plasmapheresis as a method for plasma extraction in comparison with centrifugation or gravity sedimentation. The study was designed as a cross over trial with six Freiberger horses undergoing plasma donation by plasmapheresis followed by whole-blood donation and subsequent plasma production 4 weeks later. Automated plasmapheresis and whole-blood donation were well tolerated in all horses. The plasmapheresis method achieved an almost complete removal of erythrocytes and leucocytes from plasma at all flow rates. After blood bag centrifugation, significantly more erythrocytes (P < 0.01) and leucocytes (P < 0.01) were present in the prepared plasma compared with plasmapheresis plasma. Plasma prepared by gravity sedimentation contained significantly more erythrocytes and leucocytes than plasma prepared with the other techniques (P < 0.01), and platelet aggregation was observed. The coagulation proteins and the total protein content of plasma prepared after plasmapheresis and blood bag centrifugation did not differ significantly from values measured prior to collection (P > 0.05). However, the activity of factor VIII was significantly lower 24 h after gravity sedimentation of blood than activity prior to blood collection (P < 0.01). In conclusion, automated plasmapheresis is the method of choice for the production of high quality equine plasma.

Animals↗

Impact of plasmapheresis on platelet hemostatic capacity in healthy voluntary blood donors detected by the platelet function analyzer PFA-100.

Previous flow cytometry studies showed that platelet activation may occur during cytapheresis, cardiopulmonary bypass and hemodialysis. The aim of this pilot study was to determine if the impact of plasmapheresis leads to alterations in platelet hemostatic capacity. Plasmapheresis was carried out in 30 volunteers using an Autopherese C (Baxter) and an MCS3p (Haemonetics). Blood samples were collected and analyzed immediately before and after plasmapheresis. As a result of the plasmapheresis on the Autopherese C, the mean closure time (CT) for collagen/epinephrine (Col/Epi) increased from 118.2 +/- 25.1 to 149.9 +/- 35.0 s and from 88.7 +/- 16.9 to 98.5 +/- 26.3 s for collagen/ADP (Col/ADP), respectively. Seven subjects showed impaired CTs after plasmapheresis for Col/Epi. For Col/ADP, five subjects showed impaired CTs after apheresis. Statistical analysis (McNemar test) showed a significant difference before and after apheresis for Col/Epi (P = 0.024) but not for Col/ADP (P = 0.088). Similar results were shown for plasmapheresis carried out with the MCS3p. These findings show that plasmapheresis can cause an impairment of platelet function in healthy volunteers as measured by the PFA-100, an effect of so far unknown clinical significance.

Adult↗

A prospective trial on the safety of long-term intensive plasmapheresis in donors.

BACKGROUND AND OBJECTIVES: There are still concerns about the safety of long-term intensive donor plasmapheresis, because the reasons that donors drop out of plasmapheresis programmes have not been determined in prospective studies. MATERIALS AND METHODS: Seventy-two donors were switched from a moderate plasmapheresis programme to an intensive plasmapheresis programme and observed over a 3-year period. In addition to measuring total serum protein (TSP), albumin, immunoglobulin G (IgG) and haemoglobin (Hb) levels, parameters of iron metabolism and blood coagulation, and biochemical cardiovascular risk markers, were determined at baseline and at every 15th donation. We also collected statements from donors who dropped out of the plasmapheresis programme about their reasons for withdrawal. RESULTS: Dropouts were predominantly related to socioeconomic (n = 34) or medical reasons not related to plasma donations (n = 8). Three donors had to drop out when their TSP levels fell below threshold for the third time within a 5-week period. At baseline, donors had significantly lower TSP, albumin, IgG, Hb and ferritin levels than gender-matched and age-matched non-donor controls. However, subsequent intensive plasmapheresis over 3 years did not impair the individuals' ability to donate plasma. TSP, IgG, Hb, ferritin, transferrin, cardiovascular risk markers and parameters of blood coagulation did not change significantly during the observation period. CONCLUSIONS: The reasons why donors cease to participate in intensive plasmapheresis programmes are predominantly not directly related to the plasma donation itself.

Adult↗

Plasmapheresis in Goodpasture's syndrome with renal failure.

Four patients who presented with severe proliferative glomerulonephritis associated with linear deposition of IgG on the basement membrane have been treated by intermittent massive plasmapheresis. Two patients had all the features of Goodpasture's syndrome. In the other two cases, the characteristic renal lesion was present but there was no pulmonary involvement. In all cases, renal function improved after plasmapheresis while in two, renal function deteriorated after plasmapheresis was stopped. On of these patients responded to a second course of plasmapheresis but failed to respond to a third. This study supports previous reports of the value of plasmapheresis in patients with Goodpasture's syndrome and renal failure in whom recovery without plasmapheresis has not been recorded. The present study emphasizes the importance of continuing treatment for a period of weeks to permit prolonged remission. If treatment is withdrawn too early, rapid deterioration in renal function may result, and unless plasmapheresis is recommenced at once the renal failure may then prove irreversible.

Adolescent↗

Plasmapheresis does not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. The Lupus Nephritis Collaborative Study Group.

OBJECTIVE: To determine whether plasmapheresis increases the risk for infection in immunosuppressed patients. DESIGN: Randomized, controlled trial. SETTING: Multicenter. PATIENTS: Eighty-six patients enrolled in a trial of plasmapheresis for severe diffuse proliferative lupus nephritis. INTERVENTIONS: Forty-six of the patients received high-dose steroid therapy plus cyclophosphamide therapy for 8 weeks. Thereafter, cyclophosphamide therapy was discontinued, and steroid therapy was tapered (standard treatment group). Forty patients received identical treatment and had 12 plasmapheresis procedures during the first 4 weeks of the treatment. MEASUREMENTS: Patients were examined for the development of infection. MAIN RESULTS: No statistical difference in age, sex, race, serum creatinine level, proteinuria, or complement levels was found between the two groups. Over a follow-up period of 5376 patient-weeks, 74% of patients in the standard treatment group had 62 infections, yielding an aggregate infection rate of 1.15 infections per 100 weeks (median individual infection rate, 1.08; 25th and 75th percentiles, 0.0 and 2.44). This rate was comparable to that seen in the plasmapheresis-treated patients who were followed for 4187 patient-weeks: 68% had 51 infections, for an aggregate infection rate of 1.22 infections per 100 weeks (median individual infection rate, 0.94; 25th and 75th percentiles, 0.0 and 2.32). The infection rate was also comparable in the initial acute phase of the study, despite the fact that patients who received plasmapheresis then had significantly lower immunoglobulin (IgG) levels (P less than 0.001). Neither the site (superficial compared with systemic) nor the nature (conventional compared with unconventional) of infection differed statistically between the two groups. Of 14 patient deaths, 7 were from infection (4 in control group and 3 in the plasmapheresis group). CONCLUSION: Plasmapheresis did not increase the risk for infection in immunosuppressed patients with severe lupus nephritis.

Adult↗

Removal of basiliximab by plasmapheresis.

Basiliximab is a chimeric monoclonal antibody directed against the alpha chain of interleukin-2 (IL-2) receptors. Given its expected volume of distribution (plasma volume), therapeutic plasmapheresis may be expected to lower serum Basiliximab levels. A 20-mg dose of Basiliximab was given before plasmapheresis. Blood and pheresis fluid samples were obtained to monitor Basiliximab levels. A total of three blood samples were drawn: the first was obtained 4 hours before, the second sample immediately before commencement, and the third 2 hours after cessation of plasmapheresis. A fourth sample was obtained from the removed plasma. There was an appreciable reduction in Basiliximab concentration levels after plasmapheresis. From the change in serum concentration after plasmapheresis, approximately 64.6% of circulating Basiliximab was removed. Plasmapheresis removes substantial amounts of Basiliximab. Therefore, supplemental Basiliximab should be given after plasmapheresis to maintain the desired duration of IL-2R saturation.

Antibodies, Monoclonal↗

[Does therapeutic membrane plasmapheresis increase protein synthesis?].

The objective of the investigation was to assess whether therapeutic membrane plasmapheresis accelerates protein synthesis. To this end pseudouridine (PSI), a modified nucleoside was investigated which provides information on the tRNA turnover and thus indirectly also on protein synthesis. The authors made 10 plasmapheresis on a A 2008 PF monitor with Plasmaflux P2 filters which they use to exchange 1 plasma volume of the patients. Laboratory indicators were investigated one day before plasmapheresis, on the day of plasmapheresis and during its course, and on the 1st, 2nd and possibly 3rd day after plasmapheresis. They revealed that the clearance of the plasma filter for PSI (0.41 +/- 0.04 ml/s, arithmetical mean +/- SEM) did not differ significantly from the filtration rate (0.49 +/- 0.01 ml/s, p = 0.15). As compared with the initial examination (0.49 +/- 0.06 ml/s) on the first day after plasmapheresis as a result of reduced glomerular filtration rate the renal clearance of PSI was reduced (0.33 +/- 0.05, p less than 0.01). PSI serum concentrations were therefore expressed as the serum PSI/serum creatinine ratio. This ratio was, as compared with the initial examination (80.4 +/- 4.8 nmol/mumol), raised midway during the procedure (100.8 +/- 8.6, p much less than 0.05) and after its termination (132.3 +/- 6.1, p much less than 0.01). The increase was not due to disintegration of cells or dietary factors. The rise of the serum PSI/serum creatinine ratio was due to a more rapid tRNA turnover and thus provided evidence that therapeutic membrane plasmapheresis accelerates protein synthesis.

Humans↗

Evidence for a therapeutic effect of plasmapheresis in patients with systemic lupus erythematosus.

Fourteen patients with active systemic lupus erythematosus (SLE) have been treated with plasmapheresis at a rate of two litres daily on three to four days per week, over a period of two to three weeks. Plasma was replaced isovolemically with either fresh frozen plasma or with human plasma protein fractions. Ten patients were receiving treatment with prednisone at the time of plasmapheresis, and four had received no prior treatment. Eight patients showed evidence of either clinical improvement or clinical and immunochemical improvement, at the time of plasmapheresis. In the three patients who showed high levels of circulating complexes before treatment, there was a sudden fall in the level of circulating immune complexes, which was quantitatively greater than could be explained by the amount removed. This suggests that in some patients with SLE, clearance of complexes by the mononuclear phagocytic system is initially blocked by high levels of circulating complexes and that one effect of plasmapheresis may be to relieve this blockade. Five patients showed a clinical response to plasmapheresis despite the fact that tests for immune complexes were negative. Three patients showed no response to plasmapheresis, and three were regarded as unevaluable. In a limited number of patients, who show a high level of circulating immune complexes, and whose condition is deteriorating despite treatment with corticosteroids, there may be an important therapeutic role for plasmapheresis.

Adolescent↗

Parameters for indication of plasmapheresis and the interpretation of results.

Plasmapheresis has been employed in the treatment of various immunological disorders, and its efficacy has mainly been attributed to the removal of humoral factors. Besides these effects, plasmapheresis may induce some modifications to the cellular immunological status, contributing to the restoration of altered immunological function. In immunological renal diseases various parameters may be followed to decide the use of plasmapheresis, and to judge the effect of treatment. They include clinical, functional, and morphological investigations. In patients with lupus nephritis the main indications for plasmapheresis are the presence of impaired renal function and histological signs of activity in renal biopsy. In these patients plasmapheresis is able to modify humoral and cellular immunological abnormalities. Renal function and clinical course may improve in most cases. In patients with arteritis and acute renal failure the response to plasmapheresis combined with immunosuppressive drugs is better than the response to drug therapy alone. In acute renal transplant rejection plasmapheresis may be of value in improving the graft prognosis, when humoral factors are demonstrable in the pathogenesis of graft damage and vascular lesions are present in the kidney.

Autoantibodies↗

Plasmapheresis in myasthenia gravis.

The discovery of pathogenic autoantibody of acetylcholine receptor (AChR) in the sera of patients with myasthenia gravis (MG) laid the foundation for attempting to control the disease process by removing anti-AChR antibody with plasmapheresis and reducing its rate of reaccumulation with immunosuppressive drug therapy. Plasmapheresis alone may have a favorable short-term impact in MG, and has been successfully used as a temporary measure prethymectomy, in MG crisis, and while awaiting another therapy to produce benefit. Used as a primary therapy in MG, plasmapheresis has been effective in producing stable clinical improvement and reduction of anti-AChR antibody titers only when combined with immunosuppressive drugs and administered ina protracted series of weekly, large-volume exchanges. Prednisone combined with azathioprine has been a generally effective immunosuppressive drug regimen with plasmapheresis, but neither drug by itself appears to be capable of producing stable improvement in conjunction with plasmapheresis. Cyclophosphamide, chlorambucil and vincristine also show therapeutic promise when used with plasmapheresis is selected patients. The long-term reductions in titer of antibody to AChR in MG patients attaining stable improvement indicates that cytotoxic chemotherapeutic agents may act together with prednisone under the conditions of plasmapheresis to reduce the populations of lymphoid clones with specificity for AChR.

Adult↗

[Clinical experience of automated double filtration plasmapheresis].

Double filtration plasmapheresis, one kind of fractionation plasmapheresis, was developed from membrane type plasmapheresis to remove only the pathogen and return the normal protein back to the patient. We started our automated double filtration plasmapheresis since December 1993. There were 13 patients who received one hundred treatments totally during one year period. And they are myasthenia gravis (8 patients); acute inflammatory demyelinating polyneuropathy (1 patient), multiple myeloma (1 patient); acquired factor VIII inhibitor (1 patient); autoimmune hemolytic anemia (1 patient); systemic lupus erythematous (1 patient). Technically double filtration plasmapheresis is easy to perform and time-saving. It also makes necessity of replacement fluid less frequent. Incidence of complication is rare, and this includes hypotension 2%, palpitation 1%, headache 1%, hemolysis 4%, air emboli 1%, high secondary pressure 2%, and no motality during our treatment. Clinical response is documented in cases of myasthenia gravis; acute inflammatory demyelinating polyneuropathy and acquired factor VIII inhibitor in our study. In conclusion, double filtration plasmapheresis is a time-saving, convenient, and safe therapeutic modality with rare complication. Because its effectiveness on limited kinds of diseases and costs relatively high price, thus plasmapheresis should be used in selected cases and treat aggressively if indicated.

Adolescent↗

Platelet-rich plasmapheresis in cardiac surgery: a meta-analysis of the effect on transfusion requirements.

OBJECTIVE: Our purpose was to determine whether intraoperative platelet-rich plasmapheresis in cardiac surgery is effective in reducing the proportion of patients exposed to allogeneic red cell transfusions. METHODS: A systematic search for prospective, randomized trials of platelet-rich plasmapheresis in cardiac surgery, using MEDLINE, HEALTHSTAR, Current Contents, "Biological Abstracts," and EMBASE/Excerpta Medica up to August 1997, was completed. Trials were included if they reported either the proportion of patients exposed to allogeneic red cells or the units of allogeneic red cells transfused. Trials were abstracted by 2 independent investigators and the quality of trial design was assessed with the use of a validated scale. RESULTS: Seventeen references met the inclusion criteria (1369 patients [675 control: 694 platelet-rich plasmapheresis]). Platelet-rich plasmapheresis reduced the likelihood of exposure to allogeneic red cells in cardiac surgery (odds ratio 0.44; 95% confidence interval 0.27, 0.72, P = .001). Platelet-rich plasmapheresis had a small but statistically significant effect on both the volume of blood lost in the first 24 hours (weighted mean difference -102 mL; 95% confidence interval -148, -55 mL, P < .0001) and the mean units transfused (weighted mean difference -0.33 units; 95% confidence interval -0.43, -0.23, P < .0001). However, platelet-rich plasmapheresis was only marginally effective (odds ratio 0.83, 95% confidence interval 0.34, 2.01, P = .68) for "good" quality trials, whereas it appeared very effective in trials with poor methodologic quality (odds ratio 0.33, 95% confidence interval 0.17, 0.62, P = .0007). CONCLUSIONS: Although platelet-rich plasmapheresis appeared effective in decreasing the proportion of patients receiving transfusions after cardiac operations, the quality of most of the supporting trials was low and the benefit was small in trials of good quality. Further clinical trials should be completed.

Blood Loss, Surgical↗

Kinetics of anti-peripheral nerve myelin antibody in patients with Guillain-Barré syndrome treated and not treated with plasmapheresis.

Serial anti-peripheral nerve myelin antibody titers were determined in 28 consecutive patients with Guillain-Barré syndrome during the course of their illness. Eighteen patients were treated with plasmapheresis and 10 were not. Anti-peripheral nerve myelin antibody titers in the group treated with plasmapheresis declined significantly more rapidly than in the group not treated with plasmapheresis. Five patients treated with plasmapheresis who showed initial clinical improvement, with a concurrent decline in anti-peripheral nerve myelin antibody titer, had one or two recurrences of clinical symptoms during a 2- to 8-week period associated with an increase in anti-peripheral nerve myelin antibody titer. Recurrent weakness was severe enough to prompt additional courses of plasmapheresis. The data suggest that serial determinations of antiperipheral nerve myelin antibody in patients with Guillain-Barré syndrome may identify patients with antibody rebound associated with recurrence of clinical symptoms and prolonged recovery in whom further plasmapheresis should be considered.

Adolescent↗