Double Filtration Plasmapheresis in Critical Care

Abstract: Many kinds of technologies have been introduced and successfully developed for therapeutic apheresis. Furthermore, several kinds of these technologies have also been applied in critical care. Double filtration plasmapheresis (DFPP), however, is rarely applied in this field in comparison with other treatments such as continuous hemofiltration, continuous hemodiafiltration, single filtration plasmapheresis, and plasma adsorption therapies. In this paper, the characteristics of the DFPP treatments for critical care are summarized. During the DFPP treatments, the patient's blood volume (BV) often decreases with time due to albumin loss induced by inadequate albumin infusion in a supplementation fluid. We examined the change of BV by a continuous hematocrit monitor, Crit‐Line, during an in vivo study for 9 patients. As a result, albumin loss fairly occurred in DFPP treatments. The decrease of patient BV was induced by an oncotic pressure drop due to albumin loss and often resulted in a blood pressure drop. This is a serious problem for DFPP in critical care. We should avoid inadequate albumin infusion if the patient is suffering from these adverse effects. In order to determine the optimal concentration C_S and volume V_S values of a supplemented albumin solution, we introduced a variable blood volume model for albumin transport in DFPP.     

Membranes for Therapeutic Apheresis

Abstract: Kuraray has developed many kinds of apheresis devices, such as plasma separators, plasma fractionators, and apheresis monitors. In this article, apheresis membranes, especially double filtration plasmapheresis (DFPP) and plasma fractionators used in DFPP are introduced. DFPP is both clinically and cost effective apheresis therapy, and it has been used widely for the treatment of many kinds of diseases. Several types of plasma separators with various pore sizes are available. It is important to select the proper plasma separator with suitable pore size, determined by the size of the pathogenic substances to be removed. The Evaflux 5A ethylene‐vinyl alcohol copolymer plasma fractionator efficiently separates low‐density lipoprotein from high‐density lipoprotein. DFPP with the Evaflux 5A is effective for the treatment of familiar hyperlipidemia.     

Successful Delivery in a Pregnant Woman with Lupus Anticoagulant Positive Systemic Lupus Erythematosus Treated with Double Filtration Plasmapheresis

Abstract: The case was a 29 year old female who has suffered from systemic lupus erythematosus (SLE) since 15 years of age. The activity of SLE was low, and she took prednisolone orally. Her first pregnancy failed after 14 weeks. In the second pregnancy, she had thrombocytopenia, prolonged activated partial thromboplastin time (APTT), positive lupus anticoagulant (LAC) and thus was diagnosed with antiphospholipid antibody syndrome (APS). Combination therapy with steroids and aspirin was started, and she underwent treatment of double filtration plasmapheresis (DFPP) in the early stage of pregnancy. Her platelet count increased, and the value of APTT has normalized with DFPP treatment. She delivered successfully on the 32nd week of pregnancy. We think that DFPP is an effective and safe treatment in patients with an LAC positive pregnancy.     

The Six Year Experience of Plasmapheresis in Patients with Myasthenia Gravis

Abstract: Plasmapheresis (PP) effectively removes autoantibodies in various autoimmune diseases. The use of PP in the treatment of myasthenia gravis (MG) has been widely accepted since the 1970s. The treatment protocol, however, has not been standardized. For the last 6 years, we collected a total of 94 MG patients, 38 males and 56 females aged 14–80 years, who received 175 courses of PP treatment for a total of 823 sessions. The methods we used were double filtration plasmapheresis (DF), immunoadsorption plasmapheresis (IA), and plasma exchange (PE). There were 167 courses of DF, 6 courses of IA, and 2 courses of PE. Each course of treatment consists of 4 to 5 sessions of apheresis. The processed volume of plasma is 1 calculated plasma volume. All patients tolerated PP well although 2.3% of them experienced hypotension. Our experiences are summarized as follows. Both DF and IA effectively ameliorate symptoms and signs of MG. IA removes acetylcholine receptor antibody more effectively than DF does, but clinical effects between these 2 methods are similar. A daily schedule seems more effective than an alternate daily schedule. The optimal number of PP sessions for each course is 4. The factors correlating with better clinical response are high MG score, nonthymoma patients, younger age at onset, and higher removal rate for immunoglobulin G.     

Comparative Study of Clinical Effects Between Plasma Adsorption and Double Filtration Plasmapheresis in Patients with Myasthenia Gravis

Abstract: Plasma exchange (PE) has been one of the most powerful treatments for patients with myasthenia gravis (MG) since Pinching et al. reported its clinical usefulness in 1976, despite the need for supplemental human plasma. However, new apheresis techniques, e.g., plasma adsorption (PA) and double filtration plasmapheresis (DFPP), which do not need human plasma, were developed and have been introduced for clinical use in MG. We compared the effects of these plasma purification therapies in patients with MG and found that DFPP improved such subjective symptoms as chest compression and general fatigue better than PA while both of them could decrease the serum level of acetylcholine receptor (AChR) antibodies and relieve objective muscle weakness to a similar degree. It may be that DFPP can remove some circulating pathogenic factors other than AChR antibodies more efficiently than PA.—     

Double Filtration Plasmapheresis for the Treatment of Bullous Pemphigoid: A Three Case Report

Abstract: Bullous pemphigoid (BP) is an autoimmune disease caused by an antidermal basal lamina antibody. In recent years double filtration plasmapheresis (DFPP) has been reported to be an effective therapy for BP. We experienced 3 cases of BP treated by DFPP. DFPP resulted in an improvement in clinical symptoms and remission allowing a decrease in the required dose of corticosteroid. DFPP was found to be an effective treatment for all 3 patients without noticeable adverse events resulting from DFPP. From these results it is concluded that DFPP is worth considering as an option as treatment for BP patients who were unresponsive to conventional steroid therapy, those in whom corticosteroids should be reduced or discontinued because of complications such as diabetes mellitus and/or osteoporosis.     

Rheopheresis: Rheologic,Functional, and Structural Aspects

Abstract: Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis for extracorporeal hemorheotherapy, eliminating an exactly defined spectrum of high molecular weight proteins from human plasma (e.g.: fibrinogen, α‐2‐macroglobulin, low‐density lipoprotein cholesterol, IgM). This results in the improvement of blood flow and microcirculation initiated by lowering blood and plasma viscosity, and erythrocyte aggregation. In this context, microcirculation stands not only for the patency of small blood vessels, but for the complete interactive network between plasma, blood cells, the vessel wall, and cellular and extracellular compartments of the surrounding tissue. Insufficient tissue oxygenation leads to tissue damage, e.g., a microcirculatory disorder develops, creating acute as well as chronic symptoms. Therefore, impaired microcirculation has a rheologic, functional, and structural dimension with respect to involved organs or tissues. Rheopheresis represents a specific therapeutic approach with an acute rheologic as well as chronic functional and structural effects, which was confirmed in pilot and controlled clinical studies for several organ systems. Data from 2 controlled clinical trials are available for the safe and effective treatment in patients with age‐related macular degeneration.     

Removal of Anti‐A/B Antibodies with Plasmapheresis in ABO‐Incompatible Kidney Transplantation

Abstract: Because of a shortage of cadaver donors in Japan, ABO‐incompatible living kidney transplantation has been carried out. Sixty‐seven ABO‐incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long‐term results of ABO‐incompatible LKT, graft survival of ABO‐incompatible LKT up to 3 years was significantly lower than that of ABO‐compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti‐A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti‐A/B antibody titers before and after plasmapheresis. The anti‐A/B antibody titers also were well suppressed over the long term after transplantation.     

Ability to Remove Immunoglobulins and Antiganglioside Antibodies by Double Filtration Plasmapheresis in Guillain-Barré Syndrome: Is It Equivalent to Plasma Exchange?

Abstract: The value of plasma exchange (PE) in Guillain-Barré syndrome (GBS) is well established. In Japan, patients with GBS and related diseases often receive double filtration plasmapheresis (DFPP) as well as PE. No comparative trials between PE and DFPP, however, have been conducted. We compared their abilities to remove immunoglobulins and antiganglioside antibodies to find out whether DFPP is equivalent to PE. The ability to remove immunoglobulins and antiganglioside antibodies was compared between PE and DFPP using plasma samples from 41 patients with GBS and related diseases before and after each treatment session. The ability of DFPP to remove both IgGs and antiganglioside IgG antibodies were significantly inferior to those of PE. There is a less theoretical basis for selecting DFPP as the first choice of plasmapheresis for GBS and related disorders.—     

Plasma Exchange Versus Double Filtration Plasmapheresis in the Treatment of Guillain‐Barré Syndrome

Abstract: Previous studies have shown that both plasma exchange (PE) and double filtration plasmapheresis (DFPP) are effective treatments in Guillain‐Barré syndrome (GBS). Whether PE and DFPP have similar effects in GBS is not clear. This report compares the therapeutic effectiveness of PE and DFPP in GBS patients treated in 3 major hospitals in northern Taiwan. A total of 102 patients were included in this survey, including 39 with PE (hereafter PE group) and 63 with DFPP (hereafter DFPP group). Both groups showed significant improvement of disability scores after treatment. However, time to onset of effect was shorter (5.6 ± 3.5 versus 7 ± 3.4 days, p < 0.05), and changes of disability scores were more prominent (1.3 ± 0.8 versus 0.8 ± 0.8, p < 0.05) in the PE group than the DFPP group. Mortality and outcome after 6 months were not different between the 2 groups. In conclusion, both PE and DFPP are effective treatments in GBS. PE was superior to DFPP in short‐term effectiveness. The long‐term effectiveness was not different.     

A Case Report of Double‐Filtration Plasmapheresis for the Treatment of Age‐related Macular Degeneration

An 85‐year‐old man with dry type age‐related macular degeneration (AMD) in his right eye and a disciform scar in his left eye received double‐filtration plasmapheresis (DFPP) for the treatment of his right eye. The protocol for plasmapheresis followed the Multicenter Investigation of Rheopheresis for AMD (MIRA) trial and consisted of four pulses of paired sessions of plasmapheresis with a two‐day interval within 10 weeks. The pre‐DFPP best corrected visual acuity (BCVA) for the right eye was 6/15 (0.4). Six months after DFPP treatment, the BCVA of the right eye was 6/10 (0.6) and remained unchanged at the 12th month; however, comparison of the right eye fundus picture, fluorescein angiogram, and optical coherence tomography of the macular area before and 6 and 12 months after plasmapheresis revealed no discernable changes. The per‐session and per‐course clearance rates were highest for IgM (63.8% and 90.8%) and lowest for albumin (11% and 15.4%). No plasmapheresis‐related complications, such as hypotension, hemolysis or infection, occurred. Thus, DFPP treatment can provide effective treatment for dry type AMD with minimal side‐effects.     

Apheresis Treatment in Lambert‐Eaton Myasthenic Syndrome

Abstract: The Lambert‐Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q‐type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti‐P/Q‐type voltage‐gated calcium channel (P/Q‐VGCC) antibody. The first case, a 72‐year‐old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q‐VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti‐P/Q‐VGCC antibody titers. The second case, a 73‐year‐old male presenting with leg weakness, was treated by PE and double‐filtration plasmapheresis. The P/Q‐VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q‐VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.     

More Selective Removal of Myeloperoxidase‐Anti‐Neutrophil Cytoplasmic Antibody From the Circulation of Patients With Vasculitides Using a Novel Double‐Filtration Plasmapheresis Therapy

Our aim was to investigate the removal of myeloperoxidase‐anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) from the circulation of patients with vasculitides by double‐filtration plasmapheresis (DFPP) using various primary separator and secondary separator combinations. Nineteen patients diagnosed with vasculitides positive for serum MPO‐ANCA were enrolled and received 56 sessions of DFPP. One patient received three sessions of DFPP using MPS07 (the primary filter)/EC50W (the secondary filter), nine patients received 27 sessions of DFPP using MPS07/EC20W, and the other nine patients received 26 sessions of DFPP using EC50W/EC20W. The sieving coefficients (SC) of albumin, immunoglobulin (Ig)A, IgG and IgM were measured, as well as the reduction ratio in plasma protein concentrations and MPO‐ANCA titer after a single session of DFPP. The MPS07 filter was well permeable for all the above‐mentioned plasma proteins; the EC50W and EC20W filters were permeable for albumin and IgG, less for IgA and IgM. During DFPP using MPS07/EC50W, the reduction ratio of IgG was much lower than IgM and IgA (30.5 ± 9.0% vs. 89.7 ± 5.4% and 61.7 ± 14.8%). During DFPP using MPS07/EC20W, the decline in IgM, IgA, and IgG was 94.2 ± 3.1%, 96.2 ± 2.3%, and 64.7 ± 21.0%, respectively. During DFPP using EC50W/EC20W, the decline in IgM, IgA, and IgG was 2.8 ± 12.9%, 90.9 ± 4.4%, and 43.5 ± 13.8%, respectively. The percentage reduction in MPO‐ANCA titer after a single session of DFPP using EC50W/EC20W was 34.6 ± 14.3%. DFPP using EC50W/EC20W filters may be more selective for the removal of pathogens such as IgG, with subsequently effective reduction of serum ANCA titer.     

Therapeutic Apheresis in Myasthenia Gravis

Abstract: Plasma exchange (PE) is an easily applicable technique for rapid and massive removal of antibodies, and its beneficial role is well established in the management of myasthenia gravis (MG), an antibody‐mediated disorder of the neuromuscular junction. PE is useful in myasthenic crisis, in most severe forms of MG before thymectomy, in the early postoperative period, and in cases of symptom worsening during tapering or initiation of immunosuppressive therapy. Clinical efficacy varies from 55% to 100%, and improvement rarely persists for more than 4–10 weeks; thus immunosuppressive therapy has to be associated. New apheretic techniques (double filtration plasmapheresis, immunoadsorption systems with staphylococcal protein A columns or thryptophan‐polyvinyl alcohol gel columns) that allow the selective removal of IgG and anti‐AChR antibody were recently used in the management of MG with positive effects. Whether their therapeutic effect and cost effect prove more favorable than those obtained by PE still must be demonstrated.     

Outcome of Patients on Long Term Low‐Density Lipoprotein Apheresis with Membrane Differential Filtration: A Case Study in Three Patients 14 Years on Treatment

Abstract: Membrane differential filtration (MDF) 1 , 2 is a variety of cascade filtration. Three patients with primary hyperlipoproteinemia and coronary heart disease (2 patients with foregoing myocardial infarction) were treated with MDF for a period of 14 years. The mean treatment interval was 21 days. The basic level of low‐density lipoprotein (LDL) cholesterol was about 450 mg/dl, and the level on LDL apheresis with comedication of statins was 180 to 200 mg/dl before treatment. Atherosclerosis progressed slowly during this period, and myocardial infarctions were avoided. However, in all 3 patients angiologic interventions became necessary. MDF is a well tolerated method that can be conducted without allergic hazards. The clinical results compare with those of other apheretic techniques.