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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

Plasma exchange with plasma protein fraction and lactated Ringer's solution using the continuous flow cell separator.

Ten patients underwent 50-70 percent plasma exchanges using the continuous flow cell separator. The exchange material consisted of Plasma Protein Fraction (PPF) and Lactated Ringer's Solution (LRS) instead of fresh frozen, modified or lyophilized plasma. No bleeding or other complications were encountered. The coagulation factor activity after exchange was above that required for hemostasis. The procedure is safe, expeditious and efficient.

Blood Proteins

The hemostatic imbalance of plasma-exchange transfusion.

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.

Amyotrophic Lateral Sclerosis

Plasma exchange for cold agglutinin hemolytic anemia.

Two patients with advanced lymphoma, chronic cold agglutinin disease refractory to conventional therapy and severe, progressive anemia were treated with exchange plasma transfusion. Both experienced significant reduction in titers. The first patient, in whom the procedure was done manually, died with widespread lymphoma without achieving apparent clinical benefit. The second patient was exchanged using the Aminco Celltrifuge, with improvement in in vitro compatibility tests and transfusion tolerance. The technical details of continuous-flow centrifugation exchange plasma transfusion are described.

Aged

Plasma exchange in Guillain-Barré syndrome: one-year follow-up. French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome.

We report the one-year assessment of plasma exchange (PE) versus control in Guillain-Barré syndrome (GBS), based on a randomized multicenter clinical trial of 220 patients with GBS. Treated patients received four PEs, with either albumin or fresh frozen plasma (FFP) as replacement fluid. This study completes the short-term analysis previously published (Ann Neurol 1987;22: 753-761). Long-term benefit from PE was observed, as demonstrated by full muscular strength recovery at one year: 71% in the PE group versus 52% in the control group (p = 0.007), confirmed after adjustment for four prognostic factors. FFP showed no additional benefit compared with albumin (77% full recovery in the FFP group versus 65% in the albumin group; p = 0.22). PE did not affect the incidence of severe motor disability (11% in both groups).

Adolescent

Long-term effects of repeated plasma exchange in myasthenia gravis.

Plasma exchange produces a short-term clinical improvement in myasthenia gravis (M.G.) which may be attributable to removal of acetylcholine receptor (AChR) antibody. The possibility that repeated plasma exchanges might confer cumulative long-term benefits was investigated. Serum-AChR-antibody and clinical response were followed for 4--12 months (mean 8 months) in six M.G. patients receiving 4--25 plasma exchanges of 2--4 1 together with immunosuppressive drugs (azathioprine [2.5 mg/kg] with or without alternate-day prednisone therapy), and in seven M.G. patients on immunosuppressive drugs alone. Percentage decrease in AChR antibody was not significantly different in the two treatment groups. Decline in antibody titre was associated with clinical improvement. Eight patients with previous thymoma showed significantly greater decline in antibody than the remaining five patients, irrespective of plasma exchange. Since repeated plasma exchange had no cumulative long-term benefit, the value of this treatment as used here lies only in short-term control of severe M.G. symptoms.

Acetylcholine

Reduction of blood viscosity following plasma exchange.

The effect of plasma exchange with plasma protein fraction on blood viscosity was determined in seven hyperlipoproteinaemic patients with coronary or peripheral vascular disease. This resulted in decreases in whole blood viscosity of 83% and 30% respectively at the lowest and highest shear rates studied, and decreases of 21% and 59% in plasma viscosity and fibrinogen. Serum cholesterol and triglyceride were reduced by 66% and 48% respectively. Sequential studies in two patients showed that blood viscosity returned to near-basal values by the 6th day. These findings suggest that plasma exchange may result in short-term enhancement of blood flow in vessels where low shear rates predominate.

Adolescent

Plasma exchange therapy in pediatric patients. Plasma filtration with a unipuncture technique.

Therapeutic apheresis in children is limited by technical considerations, such as circuit blood volume, venous access and hemodynamic instability. Here we report our experience with 310 plasma-filtration sessions in 44 children (aged 9 months-17 years). We used a miniaturized circuit with a unipuncture technique and a "balancing system" which assured a permanent fluid equilibrium. This procedure is well adapted to children and always made pediatric plasma exchange therapy easier and safer. The more common indications remain Guillain-Barré syndrome and acute severe glomerular diseases.

Adolescent

Intensive plasma exchange in rhesus isoimmunisation.

Intensive plasma exchanges were carried out in a 34-year-old pregnant woman to lower the level of circulating anti-D. The patient proved interesting from a number of serological aspects. The possible protective effect of coexistent ABO incompatibility is discussed. The effect of plasma exchanges on cytotoxic HLA antibodies is also demonstrated.

Adult

Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance.

BACKGROUND: Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain. METHODS: We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial. RESULTS: In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy. CONCLUSIONS: Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.

Action Potentials

Plasma exchange in immune complex disease.

The effect of plasma exchange on CIC, anti-dsDNA and complement levels and clinical activity was studied in eight patients with SLE, one with idiopathic anaphylactoid purpura and one with mixed cryoglobulinaemia. No association existed between different tests for immune complex detection. Plasma exchange as sole therapy was effective in patients with idiopathic anaphylactoid purpura and mixed cryoglobulinaemia, but not in one SLE patient with CIC. Five SLE patients with CIC treated with corticosteroids showed improvement on plasma exchange but in two patients with and two with CIC plasma exchange was not effective.

Adolescent

Thrombotic thrombocytopenic purpura and dose of plasma exchange.

Four patients with thrombotic thrombocytopenic purpura (TTP) were treated by plasma-exchange transfusion, three of whom recovered completely. Because previous reports in the literature describing exchange transfusion as treatment for TTP have demonstrated variable success rates, particular attention was given to "dose" and frequency of plasma exchange. Evans blue dye studies established a measure of "dose" under conditions of varying efficiency. Serum LDH activity was found to be diminished by plasma exchange, and the rate of return of serum LDH activity reflected residual disease activity. The magnitude of LDH activity reduction correlated with the adequacy of dose of plasma exchange and was an indicator for the need of repeated daily exchanges. Failure to obtain a spontaneous increment in platelet count also suggested the need for additional exchanges and/or larger dose of exchange. There is a need for a standard expression of dose of plasma exchange. Utilizing these markers (LDH, platelet count), it may be possible to improve the survival in TTP if adequate dose and frequency of plasma exchange are used.

Adolescent

Plasma exchange in the treatment of immune disease.

Plasma exchange was investigated as an alternative to the use of toxic drugs to remove unwanted antibody. Studies in rabbits immunized with bovine serum albumin demonstrate that exchange transfusion after a primary immunization results in a rebound of antibody to above preexchange levels. However, exchange transfusion seven, 11, or 18 days after secondary immunization results in permanent lowering of antibody levels. Plasma exchange with the continuous flow centrifuge was used in four patients with hematologic diseases. White cell isoantibodies were removed in a septic leukopenic patient, permitting white cell transfusions. Two patients with immune thrombocytopenia were exchanges; one showed prompt and permanent elevation of platelet count, while the other did not improve. A patient with immune hemolytic anemia had stabilization of hemoglobin levels and decreased Coombs reactivity following plasma exchange.

Adult

The effects of plasma exchange on cholesterol metabolism.

Four patients heterozygous for familial hypercholesterolaemia were treated by repeated plasma exchange with or without lipid-lowering drugs. Repeated plasma exchange without drug therapy in 3 patients was associated with a significant 18--28% decrement in plasma cholesterol level, comparing control with plateau values observed 3 weeks after exchange. Further decrements in plateau values followed the addition of lipid-lowering drugs used in combination, clofibrate--nicotinic acid or clofibrate--nicotinic acid--cholestyramine (range of total decrement 39--50%). Plasma exchange was associated with an increased excretion of endogenous faecal steroids, but this increase was completely abolished by the subsequent administration of clofibrate--nicotinic acid. This therapy prevented any increase in bile acid excretion with concomitant use of cholestyramine resin. Plasma exchange with drug therapy was associated with a sustained rise in plasma cholesterol specific radioactivity. In a fourth patient, clofibrate--nicotinic acid was administered prior to plasma exchange and led to a 24% fall in plasma cholesterol. Subsequent plasma exchange in this patient produced no sustained change in plasma cholesterol plateau level. In two patients, withdrawal of drugs allowed plasma cholesterol to return to pre-exchange control levels. These observations suggest that plasma exchange probably produced an increase in endogenous cholesterol synthesis and a mobilisation of tissue cholesterol. In relation to plateau cholesterol values 3 weeks after an exchange, the data suggested that the reduction in plasma cholesterol level with plasma exchange and drug therapy could have been achieved by intensive drug therapy alone.

Adult

Response to plasma exchange and splenectomy in thrombotic thrombocytopenic purpura. A 10-year experience at a single institution.

BACKGROUND: This study was designed to assess the response of patients with thrombotic thrombocytopenic purpura to plasma exchange and to evaluate the role of splenectomy after relapse. METHODS: The records of all patients with thrombotic thrombocytopenic purpura who had plasma exchange as primary treatment at a single center during a 10-year period were retrospectively reviewed. Response to the initial course of plasma exchange was determined, and the clinical outcome was evaluated in patients whose conditions were either refractory to exchange, responded without relapse, or relapsed after initial response. The outcome of patients treated during relapse with splenectomy was evaluated. A literature review was conducted to determine the clinical outcome in patients treated similarly. RESULTS: Twenty-seven patients for whom data could be evaluated had been treated in the 10-year period. Twenty-one (78%) responded to the plasma exchange, but the conditions of six (22%) were refractory and these patients died. Eight patients (30%) had one or multiple relapses after initial response but had prolonged remissions after additional plasma exchange alone (two patients) or splenectomy (six patients). A review of 19 reports, including 224 patients with thrombotic thrombocytopenic purpura initially treated with plasma exchange, revealed similar findings, with initial response in 81%, refractoriness in 19%, and relapse after initial response in 27% of patients. CONCLUSION: Response to plasma exchange in thrombotic thrombocytopenic purpura is associated with an excellent prognosis, and most deaths occur in patients whose conditions are refractory. Relapses after initial response are frequent but can be managed successfully with additional plasma exchange or with splenectomy, which often induces long-term remissions.

Adult

High volume plasma exchange in fulminant hepatic failure.

We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure > 110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Acetaminophen