Plasma exchange in neurological disease.

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.

Transfusion Medicine Equations Made Internet Accessible.

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).

Therapeutic Plasma Exchange in Tehran Between 2011 and 2014.

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.

Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura.

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.

Are the treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) effective and safe? - A Cochrane Overview summary with commentary.

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.

The establishment of in-house neurology driven therapeutic plasma exchange infrastructure in a resource-limited public hospital in Malaysia: Adopting and integrating evidenced-based health care technology through time.

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.

The conundrum of postpartum thrombotic Microangiopathy: case report and considerations for management.

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.

Our Approaches to Selective Plasma Exchange.

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.

Therapeutic plasma exchange in a tertiary care center: 185 patients undergoing 912 treatments - a one-year retrospective analysis.

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.

[The delivery of therapeutic plasma: Therapeutic plasma of today and tomorrow]. / La délivrance des plasmas. Les plasmas d'aujourd'hui et de demain.

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.

Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry.

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.

Change in therapeutic apheresis practices: Role of continuing medical education (CME).

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.

Therapy for thrombotic thrombocytopenia purpura: past, present, and future.

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.

Trends in therapeutic plasma exchange: a single-center evaluation.

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.

Pediatric therapeutic plasma exchange indications and patterns of use in US children's hospitals.

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.

Neurologic indications for therapeutic plasma exchange: 2011 update.

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.

Therapeutic apheresis in pediatrics: technique adjustments, indications and nonindications, a plasma exchange focus.

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.

Plasma exchange for renal disease: evidence and use 2011.

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.

Beyond dialysis: current and emerging blood purification techniques.

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.