Search

Purpose: To report use trends of plasma exchange (PLEX) as well as sociodemographic and medical comorbidities associated with PLEX in the United States., Design: Retrospective cross-sectional study., Participants: Adult patients (≥ 18 years) admitted for inpatient hospitalization with a primary diagnosis of optic neuritis (ON)., Methods: Data from the National Inpatient Sample database was compiled to assess PLEX use rates between 2000 and 2020. The cohorts of patients receiving PLEX versus not receiving PLEX were analyzed between quarter 4 of 2015 through 2020 (International Classification of Diseases, Tenth Revision [ICD-10], only) for patient sociodemographic variables, medical diagnoses, insurance types, hospital characteristics, cause of disease, time to therapy, length of stay (LOS), and total charges incurred., Main Outcome Measures: Incidence of ON, incidence of PLEX, demographics, diagnoses associated with PLEX therapy, total charges, and LOS., Results: From 2000 through 2020, 11 209 patients hospitalized with a primary diagnosis of ON were identified, with a significant majority managed at urban teaching hospitals. Use of PLEX increased steadily over 2 decades from 0.63% to 5.46%. Use was greatest in the western United States and least in the eastern United States. In the subset of ICD-10 cases, 3215 patients were identified. The median time to therapy of PLEX was 1 day after admission, and PLEX use was highest in patients with neuromyelitis optica spectrum disorder (NMOSD) (21.21%) and lowest in multiple sclerosis-associated ON (3.80%). Use of PLEX was associated with significantly longer LOS and higher total charges incurred. Medical comorbidities associated with PLEX included adverse reaction to glucocorticoids (adjusted odds ratio [aOR], 31.50), hemiplegia (aOR, 28.48), neuralgia (aOR, 4.81), optic atrophy (aOR, 3.74), paralytic strabismus (aOR, 2.36), and psoriasis (aOR, 1.76)., Conclusions: Over the last 2 decades in the United States, PLEX therapy for ON has increased, with the highest use in the western United States and for patients with the diagnosis NMOSD ON., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The goal of therapeutic plasma exchange (TPE) is to remove autoantibodies, pathogenic molecules, immune complexes, toxins, high concentration lipoproteins, and pathological proteins. We aimed to present the most common indication of TPE and rate of admission to the intensive care unit. From 2011 to 2014, our retrospective study was conducted including 1069 inpatients from the Tehran Blood Transfusion Center, which was responsible for performing therapeutic apheresis in all 122 hospitals of Tehran. The patients, based on their TPE indication, were classified into five groups: hematological and oncological, neurological, renal, rheumatological diseases, and all the remaining diseases. We performed 6329 procedures of TPE on 1069 inpatients. Of the patients, 479 (44.8%) were male and 590 (55.2%) female. Their age varied from a minimum of 2 years to the maximum of 93 years. Overall, the mean of TPE sessions for each patient was 5.92 ± 3.9; 415 (38.8%) patients were admitted to the intensive care unit (ICU). ASFA categories I/II indications were considered an appropriate request for TPE, and 82.97% (887) of all TPE were suitable. The most frequent categories of TPE indications are as follows: neurological, hematological, and renal diseases. Class I/II indications in the neurological diseases, myasthenia gravis (21.7%), Guillain-Barré disease (21%), and multiple sclerosis (13.3%), were the most prevalent. In the hematological category, thrombotic thrombocytopenic purpura (TTP) (14.1%) was observed to be greater than the other indications. We observed that the most prevalent illnesses are neurological (myasthenia gravis), hematological (TTP), and renal., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Plasma exchange is a highly efficient technique to remove circulating autoantibodies and other humoral factors rapidly from the vascular compartment. It was the first effective acute treatment for peripheral disorders such as Guillain-Barré syndrome and myasthenia gravis before intravenous immunoglobulin became available. The recent recognition of rapidly progressive severe antibody-mediated central nervous system disorders, such as neuromyelitis optica spectrum disorders and anti-N-methyl-D-aspartate-receptor encephalitis, has renewed interest in using plasma exchange for their acute treatment also. In this review we explain the principles and technical aspects of plasma exchange, review its current indications, and discuss the implications for its provision in the UK., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Multiple mathematical equations inform the practice of transfusion medicine. These equations apply to a wide range of topics: dosage of blood products, calculation of fluid volumes, and even specific treatment decisions (e.g. corrected count increment for determination of platelet refractoriness). The calculation of these equations can be complicated, prone to error, and time-consuming. A trusted source is needed to accurately perform these calculations 24 hours a day without error and without monetary cost. We sought to build internet-enabled calculators relevant to the practice of transfusion medicine. We partnered with MDCalc, an online host of medical calculators with 1 million monthly users in 196 countries, to design and host the calculators. The calculators guide users in the application of transfusion medicine equations by providing indications for use, inputs for the equations variables, error-checking, warnings for bad inputs, and interpretive guidance of the result. The following calculators were built: blood volume, corrected count increment (CCI), plasma dosage, cryoprecipitated antihemophilic factor dosage, approximate number of units for compatibility testing, maternal-fetal hemorrhage Rh(D) immune globulin dosage, intrauterine RBC transfusion dosage, neonatal polycythemia partial exchange, theoretical removal of a substance by plasmapheresis, sickle cell RBC exchange volume, peripheral blood stem cell collection, and a calculator relevant to donor lymphocyte infusion. Clinicians can now utilize this reputable and highly visible online source to access these common transfusion medicine equations at any time with an internet-enabled device (https://www.mdcalc.com/search?filter=transfusion+medicine)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Thrombotic thrombocytopenic purpura (TTP) is fatal in 90% of patients if left untreated and must be diagnosed early to optimize patient outcomes. However, the very low incidence of TTP is an obstacle to the development of evidence-based clinical practice recommendations, and the very wide variability in survival rates across centers may be partly ascribable to differences in management strategies due to insufficient guidance. We therefore developed an expert statement to provide trustworthy guidance about the management of critically ill patients with TTP. As strong evidence was difficult to find in the literature, consensus building among experts could not be reported for most of the items. This expert statement is timely given the recent advances in the treatment of TTP, such as the use of rituximab and of the recently licensed drug caplacizumab, whose benefits will be maximized if the other components of the management strategy follow a standardized pattern. Finally, unanswered questions are identified as topics of future research on TTP.

There has been an increase in the use of therapeutic plasma exchange (TPE) in immune-mediated neurological disorders in recent years. However, accessibility and availability of TPE remains low and costly, especially for a country with limited healthcare funding like Malaysia. With expanding clinical indications in neurological disorders, and increasingly expensive conventional immunomodulatory treatment such as intravenous immunoglobulin and monoclonal antibodies, TPE remains an effective part of first or second-line treatment. In this article, we detailed the historical aspects of the use of TPE in neurological disorders in Malaysia over the last four decades and discussed the challenges behind the establishment of the first in-house neurology-driven TPE service in the country. Local TPE database from a national neurology centre in Kuala Lumpur over the past 20 years was analyzed. We observed a remarkable three folds increase in the use of TPE at our center over the past 10 years (total 131 TPE treatments) compared to a decade prior, with expanding clinical indications predominantly for central nervous system demyelinating disorders. Besides using membrane filtration method, centrifugal technique was adopted, providing new opportunities for other clinical beneficiaries such as a neurologist driven "in-house TPE unit". However, there were real world challenges, especially having to provide services with limited funding, human resources, and space. In addition, much has to be done to improve accessibility, availability, and sustainability of TPE services at our center and nationwide. Nevertheless, even with limited resources and support, it is possible with concerted efforts to work within the confines of these limitations to establish a safe, successful, and sustainable TPE service., (© 2019 Wiley Periodicals, Inc.)

Background: Microangiopathic hemolytic anemias and thrombocytopenias in pregnant or postpartum women constitute an interdisciplinary diagnostic and therapeutic challenge in the evaluation of thrombotic microangiopathies (TMA), where urgent care must be considered., Case Presentation: We here report the case of a 21-year-old Somali woman, who was delivered by emergency caesarean section at 35 weeks of gestational age with acute dyspnea, placental abruption and gross edema due to severe preeclampsia/HELLP syndrome. After delivery, she developed acute kidney failure and thrombotic microangiopathy as revealed by kidney biopsy. The lack of early response to plasma exchange prompted extensive laboratory workup. Ultimately, the patient completely recovered with negative fluid balance and control of severe hypertension., Conclusions: This case report emphasizes the importance to differentiate between primary TMA syndromes and microangiopathic hemolytic anemias due to systemic disorders. Delayed recovery from preeclampsia/HELLP syndrome and malignant hypertension can clinically mimic primary TMA syndromes in the postpartum period.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a potentially disabling health condition., Objective: To assess the effects of different pharmacological interventions used in CIPD., Methods: To summarize and to discuss the rehabilitation perspective on the published Cochrane Overview "Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overviewof systematic reviews" by Anne Louise Oaklander, et al., representing the Cochrane Neuromuscular Group., Results: Five CSRs and 23 RCTs, reporting data on corticosteroids, plasma exchange and intravenous immunoglobulin, were considered in the overview., Conclusions: High quality trials investigating the combined effectiveness of drugs and exercise using ICF based outcomes should be encouraged.

Background: Therapeutic plasma exchange (TPE) is increasingly used throughout the world. Although the procedure itself is fairly standardized, it is yet unknown how the underlying disease entities influence the key coordinates of the treatment., Methods: Retrospective chart review. The treatment indications were clustered into four categories. Data are presented as median and interquartile (25-75%) range [IQR]., Results: Within 1 year, 912 TPE treatments were performed in 185 patients (90 female, 48.6%). The distribution of the treatment numbers to the pre-specified disease categories were as follows: transplantation (35.7%), neurology (31.9%), vasculitis and immunological disease (17.3%), and others including thrombotic microangiopathy (8.1%), critical care related diseases (5.4%), hematology [multiple myeloma] (1.1%), and endocrine disorders (0.5%). The calculated plasma volume was significantly higher in patients with vasculitis and immunological diseases (3984 [3433-4439] ml) as compared to patients treated for transplant related indications (3194 [2545-3658] ml; p = 0.0003) and neurological diseases (3058 [2533-3359] ml; p < 0.0001). This was mainly due to the differences in the hematocrit which was 30.5 [27.0-33.6] % in the vasculitis/immunological disease patients and 40.2 [37.5-42.9] % in the neurological patients; p < 0.0001. Interestingly, treatment time using a membrane based technology was significantly longer than TPE using a centrifugal device 135.0 [125.0-140.0] min vs. 120.0 [112.5-135.0] min. Furthermore, the relative exchanged plasma volume was significantly lower in the treatment of vasculitis and immunological diseases as compared to treatments of transplant related indications and neurological diseases., Conclusion: Patients with low hematocrit and high body weight do not receive the minimum recommended dose of exchange volume. Centrifugal TPE allowed faster plasma exchange than membrane TPE.

Plasma exchange (PE) therapy is the most commonly used treatment in Japan today. The issue with PE is that it removes coagulation factors and other essential molecules during the treatment process. Fresh frozen plasma (FFP) is used to replace the essential molecules which are lost. However, FFP can be a source of various complications. We have been researching an alternative method, selective PE, consisting of a membrane with smaller pores, which prevents large and essential molecules from being removed while removing waste from the patient's blood., (© 2018 S. Karger AG, Basel.)

Since plasma for direct therapeutic use comprises no cellular fraction, it has long stood for a standardized and rather simple component; meanwhile, rules for its issuing to patients have long been strict. During the very last years, there has been a paradigm shift as novel indications have raised and possible needs for distinct types of plasma depending on the missing clotting factors in the patient. During the same period of time, plasma inactivated by solvent-detergent, which was a labile component in France, has been re-qualified by European authorities as a plasma derived-drug. The French recommendations for use of plasma - though quite recently revised (2012) - are disputed by some experts and would merit a revisit. This state-of-the art manuscript aims at presenting the novel situation of therapeutic plasma and suggesting possible evolution., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: American society for apheresis (ASFA) publishes guidelines for therapeutic apheresis (TA) and physicians ordering TA procedures should be aware of the appropriate indications based on scientific evidence. Transfusion Medicine specialists (apheresis physicians) can steer physicians in right direction through CME on right indications, duration of therapy and replacement fluid. Therefore, authors reviewed, collated, and interpreted effect of formal CME interventions., Materials and Methods: Retrospective study was conducted in a large hospital in India. CME interventions to teach clinical and managerial aspects of TA were conducted in the first quarter of 2012. Sessions involved ASFA guidelines and recommendations for TA. Data was collected and changes in practice related to TA before (March 2010 to December 2011) and after (April 2012 to December 2013) the intervention was analyzed., Results: Seventy-three subjects participated in the interventions. Five hundred and eighty-nine TA procedures were performed during study period; 214 procedures in 49 patients before intervention and 375 procedures in 84 patients after intervention. After intervention there was significant improvement in indications of category I (38.7% vs. 64.3%; P = 0.004), category II (22.5% vs. 16.6%), category III (12.2% vs. 11.9%), and category IV (6.1% vs. 2.4%; P = 0.0001). Significant reduction was seen in procedures not belonging to any category from 20.5% to 4.8% (P = 0.002). Change in practices was also observed in context of duration of therapy and replacement fluid., Conclusion: CME intervention, based on the 2010 edition of ASFA guidelines for therapeutic apheresis appears to have had a positive impact on physicians TA practices., (© 2015 Wiley Periodicals, Inc.)

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA). In 2009, the Australian TTP/TMA registry was established to collect data on patients presenting with TTP/TMA throughout Australia., Aim: To summarise information on the diagnosis and management of patients with TTP collected in the first 5 years (2009-2014) of the Australian TTP registry., Methods: Registry data from June 2009 to October 2014 were reviewed., Results: Fifty-seven patients were identified with TTP (defined as ADAMTS13 activity <10%), accounting for 72 clinical episodes. ADAMTS13 inhibitor testing was performed in nine out of 57 patients (16%), reflecting the limited availability of accredited testing facilities. Sixty-seven out of 72 episodes were treated with therapeutic plasma exchange (PEx) using cryodepleted plasma (40% of episodes), fresh frozen plasma (36%) or a mixture (22%). Median exposure to plasma products was 55.9 L. PEx was commenced ≥2 days from stated diagnosis in 15% of episodes. Adverse reactions to PEx were common with documented allergic reactions (including life threatening) in 21% of episodes. Adjunctive immunosuppression was documented in 76% of episodes (corticosteroid 71% and rituximab 39%). Platelet transfusion was administered in 15% of episodes., Conclusions: Data from the Australian TTP/TMA registry suggest a heterogenous approach to the diagnosis and management of TTP in Australia over the assessed period. These observations highlight areas for improvement and standardisation of practice, including comprehensive diagnostic testing, more immediate access to PEx and a more uniform approach to adjunctive immunosuppression and supportive care., (© 2015 Royal Australasian College of Physicians.)

While clinical recognition of thrombotic thrombocytopenia purpura (TTP) has been evident for almost 90 years, the pathological basis of this disorder has only, relatively, recently been elucidated. Consequently, options for treating TTP had evolved rather slowly for many years. Despite this, current treatment practices of intensive plasma exchange often with immune modulation have seen survival rates increase dramatically. Nevertheless, the current understanding of TTP may witness the cusp of a new era for this disorder, with new and emerging treatments nearing clinical practice that specifically target the root cause of TTP. Some of these targeted approaches may even see the beginning of plasma-free treatments for TTP, with potentially faster recoveries and fewer long-term adverse effects., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: The quality of evidence supporting the use of therapeutic plasma exchange (TPE) in the treatment of individual diseases and disorders is often limited. Since we have experienced a growing variety of indications in our center we decided to make an inventory of our TPE population., Methods: Single-center retrospective inventory of adult TPE-patients during a 7-year period to determine the evolution of indications for TPE, the response to treatment, and the existing evidence supporting TPE in specified settings., Results: During a period of 84 months, 72 patients underwent 638 sessions of TPE in 91 episodes. There was no shift in frequency of TPE or level of indication. Our population consisted of 69 patients. A level I indication was seen in 41 patients (59.4%), while 14 (20.3%) had a level II indication, 8 (11.6%) had a level III indication, one had a level IV indication (1.4%) and 5 patients suffered from a condition not mentioned in the guidelines (7.2%). The response rate was inversely correlated with the level of evidence after exclusion of these 5 patients (category I 97.6%, category II 71.4%, category III 50%, category IV 0% response, p<0.01)., Conclusions: There was no shift in frequency of TPE or level of indication in our center. Controversial indications should be carefully evaluated on an individual basis and a trial of TPE cannot be solely ruled out because of lack of evidence.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease. Incomplete understanding of its pathogenesis has hindered development of targeted therapies that might alter the natural course of disease. Smoking cessation and maintenance of euthyroidism appear to reduce the rate of onset and severity of TED. Recent evidence suggests that selenium may lessen the inflammatory symptoms in mild disease. Corticosteroids remain the primary treatment for patients with moderate to severe active TED. Surgical decompression is commonly undertaken in the chronic stable phase, and only rarely in the active phase when vision is threatened by compressive optic neuropathy. Orbital radiotherapy remains an adjunctive strategy during active disease. Targeted immunotherapies have the potential to alter disease progression, but further evidence is needed to establish safety and efficacy. In this article, we review evidence from prospective therapeutic trials of several treatment modalities. We focus on moderate to severe active TED.

Extracorporeal blood purification using various techniques and hardware is a major part of the modern day practice of clinical nephrology. Although the various modalities of hemodialysis and hemofiltration are the most commonly used extracorporeal therapies in clinical nephrology, blood purification using other techniques have become necessary to remove pathogenic, toxic, or waste substances not easily cleared by hemodialysis or hemofiltration due to factors such as molecular size, protein binding, and lipid solubility. The following review is an up to date summary of extracorporeal therapies, beyond hemodialysis and hemofiltration, in current clinical use as practiced by nephrologists and others in the United States and beyond. This comprises therapeutic apheresis (plasma exchange and cytapheresis), plasma adsorption, hemoperfusion, and the bio-artificial devices., (© 2012 Wiley Periodicals, Inc.)

Over the past 37 year the role of plasma exchange in the treatment of patients with renal disease has undergone several changes. The majority of the changes for the use of plasma exchange relied on randomized control trials and delineations of mechanisms that potentially would benefit from the use of plasma exchange. Over the past 11 years plasma exchange indications for renal disease, the absolute numbers have been relatively unchanged but the indications are quite different. The Canadian Apheresis Group indicated in 2010 that TTP/HUS is still the number 1 indication at 63% of the total plasma exchange activity for renal disease but P and C ANCA Vasculitis had risen to 14% followed by renal transplant at 10%, Goodpasture's Syndrome at 6% and transplant FSGS at 5% with Cryoglobulinemia 2% and Myeloma Nephropathy had dropped dramatically to less than 1% with no cases of SLE reported. This report describes the most common indications for plasma exchange in patient's with renal disease and the evidence that supports it's use in 2011., (Copyright © 2012 Wiley Periodicals, Inc.)

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review examines the most common neurologic indications for TPE. It focuses on Guillain-Barre' syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy (PML). As with any treatment, the proven efficacy, cost, side effects, and availability must be considered before initiation of therapy., (Copyright © 2012 Wiley Periodicals, Inc.)

Therapeutic Apheresis procedures are associated with multiple and unique challenges in children. The procedures are often performed using evidence or experience extrapolated from adult clinical practice, which may not be evidenced based. In addition to the clinical challenges, relevant psychological issues, modification of protocols and technical hardware are often necessary for safe and effective treatment in children. The following review addresses these aspects of therapeutic apheresis in children as presented at the Therapeutic Apheresis Academy in September 2011. Because of the variety of therapeutic apheresis procedures that can be performed in children, for the purposes of this review, an emphasis will be on the performance of plasma exchange in children., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Therapeutic plasma exchange (TPE) has been increasingly used over the past decade as a first-line and lifesaving treatment for various conditions classified by the American society for apheresis (ASFA). To date, the degree to which utilization of TPE in pediatrics mirrors recommendations is unknown., Methods: Using inpatient administrative data from 42 children's hospitals we conducted an 8-year retrospective cohort study of children (≤18 years) with an international classification of diseases-9-clinical modification (ICD-9-CM) discharge diagnosis indicating an ASFA Category I or II condition, or a procedure code indicating receipt of TPE during hospitalization., Results: TPE was performed during 4,190 hospitalizations of 3,449 patients, of whom 310 (9.0%) and 77 (2.2%) had a primary discharge diagnosis of an ASFA Category I or II condition, respectively. Rates of TPE use for Category I conditions were highest for children with thrombotic thrombocytopenic purpura (TTP), Goodpasture's syndrome, and myasthenia gravis. TPE use in children's hospitals significantly increased from 2003 to 2010, but TPE was performed during only 13.4 and 9.3% of hospitalizations for ASFA Category I and II conditions, respectively. There was significant between-hospital variation in the use of TPE for Category I conditions as a group and individual Category I conditions including TTP., Conclusion: We found low levels of TPE use across hospitals for key indications, including TTP, a condition for which TPE is considered a first-line and life-saving procedure. The variation identified may contribute to varying clinical outcomes between hospitals, warrants further investigation, and represents an important opportunity to improve quality of care., (Copyright © 2012 Wiley Periodicals, Inc.)

Results from recent trials and advances in the fields of medicine and technology have altered the spectrum of indications for use of therapeutic plasma exchange. In this article we analyze changes in indications for therapeutic plasma exchange that have occurred during 27 years in Croatia. We retrospectively analyzed the database of the Department of Dialysis at the University Hospital Center, Zagreb (678 patients; 6596 procedures), for changes in indications for therapeutic plasma exchange from 1982 to 2008. The number of patients and procedures increased several-fold during the follow-up period, but the mean number of procedures per patient per year did not change significantly. Neurological disorders constituted the largest group of indications for therapeutic plasma exchange (66% of all indications), followed by hematological (16%), nephrological (6%), and rheumatological disorders (6%). Myasthenia gravis was the most frequent indication during the entire follow-up period, but the pattern of other indications changed, with the most frequent at the beginning of follow-up becoming the least frequent at the end of follow-up. The five most frequent indications represented 62.2% of all indications at the beginning of follow-up, whereas during the 1990s, this percentage increased to more than 90% of all indications. Since the year 2000, the spectrum of indications has grown, and the percentage of the five most common indications decreased to 79.9%. Despite changes in indications for therapeutic plasma exchange, this procedure is still applicable in various medical fields, either traditional or newly created with the development of medicine and technology., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

Objective: Both IV immunoglobulin (IVIg) and plasma exchange (PLEX) are immunomodulatory treatments used to treat patients with myasthenia gravis (MG), but the choice of which treatment to administer to patients is limited due to lack of evidence from adequately powered, masked, randomized, standardized trials., Methods: We randomized 84 patients with moderate to severe MG defined as a Quantitative Myasthenia Gravis Score for disease severity (QMGS) of >10.5 and worsening weakness to IVIg (Gamunex®, Talecris Biotherapeutics) 1 g/kg/day for 2 consecutive days or PLEX (Caridian Spectra) 1.0 plasma volume exchanges for 5 exchanges. The patients were evaluated at day 14 after treatment for the primary efficacy parameter of change in QMGS and secondary clinical and electrophysiologic parameters and were followed for a total of 60 days., Results: Both IVIg and PLEX reduced the QMGS, and IVIg was comparable to PLEX in efficacy. The dropout rate was the same for both treatment arms and both treatments were well-tolerated. The presence of acetylcholine receptor antibodies and greater baseline disease severity predicted a better response to therapy. The postintervention status revealed that the same proportion of patients improved with treatment: 69% on IVIg and 65% on PLEX. The duration of improvement was similar with both treatments., Conclusions: IVIg has comparable efficacy to PLEX in the treatment of patients with moderate to severe MG. Both treatments are well-tolerated, and the duration of effect is comparable. Either treatment may be offered to patients depending on availability of resources., Classification of Evidence: This study provides Class I evidence that IVIg and PLEX have comparable efficacy and are equally tolerated in adult patients with moderate to severe MG within 2 weeks of treatment., (Copyright © 2011 by AAN Enterprises, Inc.)

Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation., (Copyright 2010 S. Karger AG, Basel.)

Massive transfusion (MT) is used for the treatment of uncontrolled hemorrhage. Earlier definitive control of life-threatening hemorrhage has significantly improved patient outcomes, but MT is still required. A number of recent advances in the area of MT have emerged, including the use of "hypotensive" or "delayed" resuscitation for victims of penetrating trauma before hemorrhage is controlled and "hemostatic resuscitation" with increased use of plasma and platelet transfusions in an attempt to maintain coagulation. These advances include the earlier use of hemostatic blood products (plasma, platelets, and cryoprecipitate), recombinant factor VIIa as an adjunct to the treatment of dilutional and consumptive coagulopathy, and a reduction in the use of isotonic crystalloid resuscitation. MT protocols have been developed to simplify and standardize transfusion practices. The authors of recent studies have advocated a 1:1:1 ratio of packed RBCs to fresh frozen plasma to platelet transfusions in patients requiring MT to avoid dilutional and consumptive coagulopathy and thrombocytopenia, and this has been associated with decreased mortality in recent reports from combat and civilian trauma. Earlier assessment of the exact nature of abnormalities in hemostasis has also been advocated to direct specific component and pharmacologic therapy to restore hemostasis, particularly in the determination of ongoing fibrinolysis.

Plasma exchange is a therapeutic procedure commonly used in various neurological disorders. Here we review its current role as a treatment option in diseases of the central and peripheral nervous system.

This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B-cell surface-membrane-marker CD20.

Plasma exchange can remove putative pathogenic autoantibodies and circulating immune complexes from the blood of patients with systemic lupus erythematosus (SLE). However, their efficacy has only been supported by noncontrolled and/or retrospective studies. Nonetheless, PE may still be of relevance in some selected SLE patients and as adjunctive therapy, in combination with corticosteroids (CS) and other immunosuppressant(s). We review herein the principal historical steps of the use of plasma exchange to treat SLE, based upon the main trials and case reports that have highlighted its most pertinent indications. Acute life-threatening manifestations and severe therapy-resistant manifestations, like refractory SLE renal disease, diffuse alveolar hemorrhage, neuropsychiatric SLE, thrombotic thrombocytopenic purpura, catastrophic antiphospholipid syndrome, hyperviscosity syndrome and cryoglobulinemia, are the indications for which plasma exchange might have a beneficial therapeutic role. Although few SLE patients undergo plasma exchange each year nowadays (10-20 per year in France), adverse events are very rare and recent advances in plasma exchange technologies, like immunoadsorption, might, in the future, counterbalance their cost and broaden their place in the therapeutic armamentarium for SLE.

This paper reviews recent treatment strategies of immune mediated neuropathies, in particular it includes data regarding Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), neuropathy with IgM monoclonal gammopathy and other dysglobulinemic neuropathies. In the treatment of Guillain- Barré syndrome, there is no significant difference between IVIg, plasma exchange or plasma exchange followed by IVIg. However, for reasons of convenience and safety, IVIg is used as standard treatment in most centers. There is so far insufficient evidence for the use of corticosteroids in the therapy of GBS. In treating CIDP corticosteroids, intravenous immunoglobulin and plasma exchange seem to be equally effective. However, the high costs and relative lack of availability of IVIg, the only short-term benefit and the invasive nature of the plasma exchange procedure, and on the other hand serious long-term side effects of corticosteroids are the most important disadvantages of these treatments and have to be taken into consideration before a decision about therapy can be made. In multifocal motor neuropathy the intravenous immunoglobulin therapy is the only treatment that has been shown to be effective in controlled trials. However, inadequate response in a proportion of patients, high cost and variable availability of IVIg show the need for the search of adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may improve after treatment with chemotherapeutic agents, though the long-term effects are not known. In addition, such treatment modalities may be associated with serious side effect and even severe toxicity. Recent data support the use of a new promising drug: Rituximab, a monoclonal antibody directed against the B cell surface membrane marker CD 20.

Purpose of Review: This review examines the literature published on therapeutic plasma exchange during 2002. The review was performed by searching Medline for pertinent articles., Recent Findings: One hundred thirty articles were identified, of which 11 are reviewed. During the period, reviews of the use of therapeutic plasma exchange for managing Guillain-Barré syndrome and myasthenia gravis were published. A large randomized trial of the use of plasma exchange to treat sepsis also appeared. Finally, a large case series of the use of plasma exchange in Wegener granulomatosis was published., Summary: The literature confirms the use of plasma exchange for Guillain-Barré syndrome but suggests that inadequate evidence exists to support its use for long-term improvement in myasthenia gravis. The study of patients with severe sepsis suggests that plasma exchange may benefit a subset of patients, those with abdominal infections. Finally, plasma exchange for Wegener granulomatosis with severe renal dysfunction appears not to offer any benefit over immunosuppressive therapy.

The French plasma exchange registry created in 1985 lists the indications, techniques and complications of the French therapeutic haemapheresis. In 2001 it contains the data of more than 16,700 patients for a total of 153,641 sessions. The indications concern five groups of pathologies (neurology, haematology, nephrology, vasculitis, and endocrinology). Until 2000, the neurology represented the most important group but the use of the high dose IgIV for Guillain-Barre and myasthenia gravis decreased the indications. The haematology became most important group treated because of the increase of the TTP and HUS number treated. The endocrinology (familial hypercholesterolemia) represents at present 10% of the patients treated for 18.7% of the sessions. The vascular access little changed since 1985, the peripheral venous access being the most used. The plasma substitution initially based on the albumin alone was gradually replaced by an association albumin macromolecules, in particular hydroxyethylstarch since 1990. After the observation of the side effects due to starches we observed an increase of the albumin alone use. The immediate complications decreased in half in 15 years. The French plasma exchange registry is the largest world database of haemapheresis with the cooperation of about 80 centres, allowing numerous scientific studies.

The French Registry for plasma exchange (PE) was set up in 1985. For 14 years it has allowed analysis of the techniques used along with the indications and complications. Recent analysis shows a slight fall in activity as some studies have ended, while the neurological disorders remain the most frequent indications for PE. The important changes observed over the years are the increased use of the centrifugation technique, the development of plasma and whole blood treatment and plasma substitution using a mixture of albumin and pentastarch. The French Registry for PE is the largest such database which, along with the Canadian Registry for therapeutic hemapheresis, allows both retrospective and prospective studies.

The concept of removal of blood "blood letting" was practised in ancient times. In the last four decades plasmapheresis, plasma exchange, or apheresis as the modality of treatment of certain specific disorders has become available. This article is a review of the principles of plasmapheresis. The equipment needed, the technique of plasmapheresis and guidelines for its use are discussed.

In 1997, the Canadian Apheresis Group reviewed data on 103,416 plasma exchange procedures that had been collected since 1980. Although the number of plasma exchanges gradually increased (from 3189 to 8208 per year), the pattern changed. In 1981, the five most frequent indications for plasma exchange resulted in 55% of all such procedures; by 1997, the five most frequent indications for plasma exchange resulted in 81.1% of all such procedures. During this period, three conditions that were originally among the most frequent indications for plasma exchange became among the least frequent. This paper reviews the published evidence that supports or refutes the use of plasma exchange in the category of the five most frequent indications from 1981 to 1997: thrombotic thrombocytopenic purpura, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Waldenstrom macroglobulinemia, the Guillain-Barre syndrome, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. For most disorders, use of plasma exchange procedures is correlated with published evidence, and the changing patterns of plasma exchange use by members of the Canadian Apheresis Group reflect published evidence. Annual center-by-center reviews of use of plasma exchange may also have influenced practice patterns.

Today, clinicians can choose from a variety of extracorporeal immunomodulatory procedures such as plasma exchange, double filtration, immunoadsorption, chemoadsorption, photopheresis, and cytoapheresis. The mechanisms underlying extracorporeal immunomodulation (ECIM) comprise removal of pathogenic antibodies and circulating immune complexes as well as reticuloendothelial system deblockage; modification of immune complex structure and processing can be induced by changing the antigen/antibody ratio and by modulation of immune complex solubility via complement activation. Finally, cellular components like lymphocyte subsets, can be modified. Clinical examples of ECIM include lupus erythematosus, Goodpasture's syndrome, anti-neutrophil cytoplasmatic antibodies-mediated systemic vasculitis, myasthenia gravis, and, hypothetically, sepsis.

The French Registry for Haemapheresis created in 1985 allows an analysis of the changing indications and techniques of plasma exchange. The data collection system has been improved since 1991 with the development of a telematic network which greatly shortens the delay to data analysis. The 8-year report shows an increase in the use of the centrifugation technique, with citrate anticoagulation alone, a very sharp decline in the use of plasma substitution with albumin alone largely replaced by combined albumin, and no change in vascular access. Indications are now dominated by the constant increase in the use of plasma exchange for neurological diseases, a relative stability in the field of haematology and a drop in the number of indications for connective tissue diseases and nephrology. Advances in the technique have led to a decline in complications observed earlier. The French Registry for Haemapheresis is the world's largest data base on plasma phoresis. Participation via telematic access is essential for further extension of the registry.

In conclusion, the development of the cell separator which can isovolumetrically remove specific components from the blood has opened a new avenue of research and therapy for patients with a variety of disorders. The techniques are relatively safe and rapid, but still exceedingly expensive. The indications and efficacy of cytapheresis appear relatively clear. The role of lymphocytapheresis in various disease states is still under investigation. Plasma exchange currently must be considered a palliative procedure, but clear and prolonged benefit has resulted in a few instances. The expense will not make this a practical approach in many instances. A combination of immunosuppressive therapy with plasma exchange will evolve as a more appropriate treatment in many instances. Finally, the removal of specific substances from the plasma by immunoadsorption columns should have the advantage of less side effects, less depletion of normal elements of the plasma, and more specifically targeted therapy.

The development of the therapeutic plasmapheresis reaches from the beginnings of the centrifugation technique in the early fifties and the appearance of membrane plasma filters in the late seventies up to numbers of treatment of about a quarter of a million a year all over the world. Instead of the former uncritical euphoria in the selection of patients nowadays a strict indication occupied the position. Efforts all over the world to confirm scientifically the efficacy of the plasmapheresis have not been finished up to now. Geographical differences in the diagnosis are in most cases the sequels of subjective factors of locally dominating working teams, which is demonstrated on the basis of international statistics. Specific modifications such as cascade filtration and plasma absorption are described.