Therapeutic plasma exchange performed in tandem with hemodialysis without supplemental calcium in the apheresis circuit

Therapeutic plasma exchange (TPE) and hemopoietic progenitor cell (HPC) collection are apheresis procedures that can safely be performed in tandem with hemodialysis. Despite the return of citrate‐anticoagulated blood to the patient during HPC collection, it is not necessary to administer supplemental calcium during these procedures because the ionized calcium concentration is restored as the returning blood passes through the dialyzer. It is not known whether this applies to TPE, in which a mixture of blood and pharmaceutical albumin, an avid binder of plasma ionized calcium, is returned to the patient through the dialyzer. We report on three dialysis‐dependent patients who required TPE and underwent tandem treatments without supplemental calcium in the apheresis circuit. Overall, ionized calcium fell 4–12% (P = 0.0.024) and patients reported no symptoms of hypocalcemic toxicity. Tandem hemodialysis/TPE can be performed without supplemental calcium in the apheresis circuit. J. Clin. Apheresis 32:154–157, 2017. © 2016 Wiley Periodicals, Inc.     

Therapeutic plasma exchange in non-hematooncological disorders in pediatrics: A single center experience

The use of therapeutic plasma exchange in the pediatric age group is mostly based on retrospective, single-center experiences. The decision to implement apheresis in pediatric patients is usually adopted from the results of studies on adult patients. In order to expand the limited data on pediatric TPE in general and non-hematooncological disorders in particular, we retrospectively evaluated TPE experience in pediatric patients who underwent the procedure for reasons other than hematooncological disorders. A total of 160 sessions in 34 patients (21 females and 13 males) with a median age of 7 (1–17) were analyzed. Most of the patients had sepsis and organ failure (12 patients, 35 procedures). In only one patient (2.9%) with methyl malonic aciduria (MMA) and sepsis, the procedure was terminated due to a grade 3 allergic reaction. Among the study cohort, 4 patients passed away. No patient died due to complications of TPE. The relatively low discontinuation rate and the lack of procedure-related mortality indicate that TPE is generally well tolerated in the pediatric age group similar to the adult population. However, since there are very limited evidence-based data on TPE use, especially in the pediatric age group, retrospective case series may also be helpful for clinicians in the decision-making process.     

The single center registry for therapeutic apheresis in Turkey: 11-year activity

Therapeutic apheresis (TA) is used as primary and adjunctive therapy in the treatment of several diseases and syndromes. We retrospectively evaluated the results of therapeutic apheresis (TA) including therapeutic plasma-exchange (TPE), double filtration plasmapheresis (DFPP), therapeutic thrombocytapheresis and leukocytapheresis as 11-year activity during 2000-2011. A total of 845 TA procedures were performed in 114 patients (67 male and 47 female, with mean age 51±17 years). Adverse events (AE) were seen in 8.6% of procedures. None of the patients died from any complication. TA is safely carried out in our center in several diseases which are similar to previous reports.     

Therapeutic plasma exchange and pregnancy: A case report and guidelines for performing plasma exchange in a pregnant patient

Therapeutic plasma exchange (TPE) has been demonstrated to be of significant clinical value in a number of diseases and conditions, with well‐established guidelines and recommendations. However, technical support in providing this procedure for pregnant patients is largely absent from these recommendations, leaving therapeutic apheresis practitioners without guidance to safely and adequately treat appropriate conditions in this important patient population. Here, we describe our experience in treating a 35‐year‐old pregnant patient with relapsing‐remitting multiple sclerosis with TPE. Additionally, we outline the principle considerations when developing her treatment plan, and we provide recommendations for apheresis practitioners when performing TPE in pregnant patients. J. Clin. Apheresis 32:191–195, 2017. © 2016 Wiley Periodicals, Inc.     

Establishing an institutional therapeutic apheresis registry

Apheresis was first performed as a therapeutic procedure in the 1950s. The first national therapeutic apheresis (TA) registry was established in Canada in 1981 and other national registries followed, including two attempts at establishing an international TA registry. There is no national registry in the United States. Our large, academic, tertiary hospital has a very active TA service. We created a TA database to track all procedures performed by the apheresis service by transferring data from paper appointment logs and the electronic medical records into a Microsoft Access database. Retrospective data from each TA procedure performed at UAB from January 1, 2003 through December 31, 2012 were entered, including the type of procedure, indication, date, and patient demographics. Microsoft Excel was used for data analysis. During the 10‐year period, our TA service treated 1,060 patients and performed 11,718 procedures. Of these patients, 70% received therapeutic plasma exchange (TPE), 21% received extracorporeal photopheresis (ECP), 4.5% received red cell exchange (RCE), 4.2% received leukocytapheresis, and 0.6% underwent platelet depletion. Among the procedures, 54% were TPEs, 44% were ECPs, 1.3% were RCEs, 0.5% were leukocytaphereses, and 0.1% were platelet depletions. According to the current literature, national and international TA use is underreported. We believe that the UAB TA registry provides useful information about TA practices in our region and can serve as a model for other institutions. Furthermore, data from multiple institutional registries can be used for clinical research to increase the available evidence for the role of TA in various conditions. J. Clin. Apheresis 31:516–522, 2016. © 2015 Wiley Periodicals, Inc.     

Complications of therapeutic apheresis in pediatric kidney transplantation

In the setting of kidney transplantation, therapeutic apheresis (TA) is employed both for pre-intervention procedures and during the post-transplant period. In pediatric nephrology units, TA is usually performed as a therapeutic plasma exchange (TPE) with dialysis equipment, and using non-plasma replacement fluids. In children undergoing kidney transplantation, complications of TPE are mainly related to its depletive properties combined with the iatrogenic immunodeficiency status of the patient. Moreover, the use of small central venous catheters and the equipment standardized for adults can increase the risk of adverse events. Focusing on these preconditions, TA in kidney-transplanted children should be performed in specialized centers with specific protocols and a trained staff.     

Apheresis in patients with sepsis: A multicenter retrospective study

Background and objectivesTo consider the effectiveness of apheresis, which is a supportive treatment method, in sepsis.Materials and methodsA hundred and eleven adults with sepsis or septic shock were included in this retrospective study. The demographic characteristics of the patients, the focus and source of infection causing sepsis or septic shock, characteristics of the pathogen, Acute Physiological and Chronic Health Assessment (APACHE) II score, routine laboratory values, which apheresis method was used, the characteristics of the replacement fluids used during the apheresis procedure, the number of apheresis procedures, complications related to the apheresis procedure, the follow-up time after the procedure, and mortality were recorded. The primary outcome was 28-day mortality.ResultsSixty-nine (62.2 %) of the patients were male. The mean age of the patients was 47.7 ± 18.6 years. The most common source of sepsis was hospital-acquired (79.3 %), the most common pathogen causing sepsis was gram-negative bacteria (41.4 %), and the most common infection site was the respiratory tract (58.7 %). The median APACHE II score was 19 (13−24). 92 (82.9 %) of the patients had septic shock. Theropeutic plasma exchange (TPE) was performed in 11.7 % of the patients and immunoabsorbtion IA in 88.3 %. The median number of sessions was 3 (3−5). No procedure-related fatal complication was observed in the study. While 28-day mortality was 61.3 % in all patients, when the mortality according to the apheresis procedures was examined, it was 11.3 % and 88.2 % in the patients who underwent TPE and IA, respectively. The most common cause of mortality was multiorgan failure.ConclusionsApheresis in sepsis can be considered as a salvage treatment. The indication for apheresis in sepsis is still at the level of patient-based individualized decision in line with the studies done so far, including our study. However, there is a need for a multicenter randomized controlled study with a large number of patients in order to give positive or negative recommendations about its effectiveness.     

The use of 50% albumin/plasma replacement fluid in therapeutic plasma exchange for thrombotic thrombocytopenic purpura

Background: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by a deficiency of von Willebrand factor‐cleaving protease (ADAMTS13) and is often associated with the presence of an antibody inhibiting the activity of the protease. Typically, 1–1.5 plasma volume exchanges are performed daily until symptoms have resolved and the platelet count exceeds 150,000/µl. Plasma is the usual replacement fluid as it provides a source of functional ADAMTS13, thus exposing patients to large volumes of plasma. Historically, Puget Sound Blood Center (PSBC) has performed therapeutic plasma exchange (TPEs) for TTP using 5% albumin for the first half of the procedure followed by plasma for the remainder. We sought to assess the efficacy of this approach. Study Design and Methods: All TPEs performed for the diagnosis of TTP by the PSBC apheresis service from January 1, 2004 through December 31, 2011 were reviewed. Response time, remission rates, relapses, and adverse events were evaluated for those patients with documented ADAMTS13 levels ≤10%. Comparisons were made with published data on TTP patients treated using 100% plasma replacement. Results: Twenty‐one patients required a median of 11 TPEs. Median time to response was 14 days. Ninety percent of patients responded to TPE. Among patients achieving remission, 53% relapsed. Out of 283 total procedures, there were 74 procedures with a documented adverse event (26%), mostly mild allergic reactions. Conclusions: TPE with an albumin/plasma replacement is safe and well‐tolerated. Remission and relapse rates were comparable to those reported using 100% plasma replacement. J. Clin. Apheresis, 28:416–421, 2013. © 2013 Wiley Periodicals, Inc.     

Predictability and efficacy of therapeutic plasma exchange for hypertriglyceridemia induced acute pancreatitis

BackgroundHypertriglyceridemia induced acute pancreatitis is associated with more severe clinical course than acute pancreatitis caused by other etiologies. Therapeutic plasma exchange (TPE) is a potential treatment for patients with severe hypertriglyceridemia induced acute pancreatitis due to its rapid effect in lowering triglycerides (TG) levels and reducing inflammatory cytokines. However, clinical data regarding the effectiveness and safety of TPE is limited.MethodsWe retrospectively reviewed eight cases of hypertriglyceridemia induced acute pancreatitis and treated with TPE. Patients' demographic data, personal history, clinical course, laboratory results, apheresis data and clinical outcome were collected and analyzed.ResultsAt initial presentation, the average TG levels for the eight patients was 3381.6 mg/dl (SD: 1491.6 mg/dl). Twelve procedures were performed on the eight patients in the study, and TG levels decreased by an average of 2673.2 mg/dl (SD: 2306.3 mg/dl) with a corresponding average reduction rate of 60.3 % (SD:21.1 %), ranging from 14.6%–84.9%. A 60 % or greater reduction was achieved in 66.7 % of all the procedures; however, the degree of reduction for each procedure was not predictable, even among repeat procedures on the same patient.ConclusionsOur study indicates that TPE is an effective and safe treatment option for patients with hypertriglyceridemia induced acute pancreatitis. However, due to the unpredictability of TG removal, repeat procedures may be necessary for some patients.     

Plasma exchange for heparin-induced thrombocytopenia in patients on extracorporeal circuits: A challenging case and a survey of the field

Current management of heparin-induced thrombocytopenia (HIT) involves prompt discontinuation of all heparin products and concomitant initiation of a direct thrombin or anti-Xa inhibitor for anticoagulation. In the setting of HIT complicated by an urgent need for cardiopulmonary bypass (CPB), the safety and the efficacy of short-term heparin-based anticoagulation after therapeutic plasma exchange (TPE) have been previously demonstrated. Patients with HIT requiring TPE are frequently on extracorporeal circuits (either CPB, extracorporeal membrane oxygenation [ECMO] or external ventricular assist devices [VADs]). Performing TPE in parallel with these circuits involves additional consideration for circuit size, anticoagulant/citrate management, as well as flow rates, and risk of air embolus. We report a case of a patient with HIT on external biventricular assist device (BiVAD) requiring urgent CPB who experienced thrombotic and hemolytic complications related to anticoagulation management around apheresis line placement for TPE. We also present results from a national survey of academic apheresis services regarding specific practices in managing patients with HIT on extracorporeal circuits who require TPE. In addition, we demonstrate the utility of TPE in patients with HIT on extracorporeal circuits and the risks of this procedure and the need to develop practice guidelines.     

Impact of the hematocrit value of the blood prime unit on patient hematocrit values after therapeutic plasma exchange in children weighing 10 kg or less

We report the impact of measuring the hematocrit (HCT) of blood prime units (BPUs) on postprocedure patient HCT values in a small child with transverse myelitis undergoing therapeutic plasma exchange (TPE). Initially, the BPU HCT values were not measured, according to our apheresis policy of using our blood center's estimated HCT value. This approach resulted in unexpected increasing elevations of our patient's post-TPE HCT after the first two TPE procedures. Subsequent measurement of the BPU HCT prior to use stabilized the patient's post-TPE HCT. To our knowledge, this is the first case report describing the impact of using the measured BPU HCT vs the estimated HCT for very small children undergoing therapeutic apheresis. Our standard operating procedure for very small children has been updated after this patient's case to include measurements of the HCT values of BPUs for children who weigh 10 kg or less.     

National survey of hemapheresis practice in Turkey (1998)

The Turkish Apheresis Group has maintained a national registry for apheresis activities since 1997. The hemapheresis practice of Turkey in 1998 is summarized in brief detail in this article. A total of 30, 136 apheresis procedures were performed at 31 different apheresis centers. At 10 centers, 145 peripheral blood stem cell (PBSC) apheresis were performed on 82 patients in allogeneic setting and at 17 centers, 981 PBSC apheresis were performed on 271 patients in autologous setting. Frequently observed adverse effects during PBSC apheresis were mild tremor and chills, paresthesia and nausea in 15% of the patients and donors. Vascular access complications, particularly observed in autologous setting due to central venous catheters were encountered in 10% of the procedures. Eight hundred and sixty-nine therapeutic plasma exchange procedures were performed at 21 centers on 172 patients, most commonly for neurological disorders and thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Therapeutic cytapheresis procedures like leukapheresis, plateletapheresis and erythrocyte apheresis were performed especially for cytoreduction in myeloproliferative disorders. A total of 204 cytapheresis procedures (66% leukapheresis, 33% plateletapheresis and 1% erythrocytapheresis) were performed on 134 patients in 15 centers. Donor plateletapheresis was the most used apheresis procedure, reaching a total of 28.016 in 1998. Many university hospitals and a few state hospitals are performing above-mentioned apheresis procedures with great success and acceptable side effects. According to these data we are planning prospective trials and will establish National Standards of Practice.     

Comparison of plasma exchange performances between Spectra Optia and COBE Spectra apheresis systems in repeated procedures considering variability and using specific statistical models

Repeated therapeutic plasma exchange (TPE) procedures using centrifugation techniques became a standard therapy in some diseases. As the new device Spectra Optia (SPO; Terumo BCT) was available, we studied its performances in repeated procedures in 20 patients in three apheresis units. First we analysed the performance results obtained by SPO. Second we compared the performances of the SPO device to a standard device, COBE Spectra (CSP; Terumo BCT) in the same patients using statistical method of mixed effects linear regression that considers variability between patients, centres and apheresis procedures.The performances analysed were classified according to plasma removal performances and their consequences on patients whose blood disturbances were assessed. Primary outcome was plasma removal efficiency (PRE) and PRE-anticoagulant corrected which was a more accurate parameter. Secondary outcomes corresponded to the volume of ACD-A consumed, platelets content in waste bag, procedure duration and status of coagulation system observed after TPE sessions.Before comparing the performances of both devices we compared the plasma volumes (PVs) processed in both techniques which showed that the PVs processed in SPO procedures were lower than in CSP procedures. In these conditions the statistical analysis revealed similar performances in both apheresis devices in PRE (p = ns) but better performances with SPO when considering higher PRE corrected by anticoagulant volume used (p < 0.05). Comparison of secondary outcomes showed no difference after SPO and CSP. After verifying that pre-apheresis patients' coagulation blood levels were identical before SPO and CSP, we showed identical haemostasis disturbances after SPO and CSP but lower platelet losses and higher fibrinogen post-apheresis blood levels after SPO (p < 0.05).No side effects or technical complications occurred during and after SPO and CSP. This study demonstrated that the Spectra Optia device is an alternative device to today's standard, the COBE Spectra device.     

Scope and application of therapeutic apheresis: Experience from a tertiary care hospital in North India

Background

We present here our experience with therapeutic apheresis (TA) performed for various indications, clinical response and complications in a tertiary care center over last 10 years.

Study design and methods

Present study is a retrospective analysis of 492 TA procedures performed for 125 patients from January 2000 to December 2009. For each patient: age, gender, weight, clinical indication, pre-procedure hematological profile and ionized calcium levels were recorded. For every procedure following parameters were analyzed: type of venous access (central/peripheral), volume of blood and plasma processed, amount of anticoagulant used, procedure duration, blood flow rate, type of replacement fluid given, response to therapy and adverse reactions.

Results

Of 492 TA procedures, 68.8% were performed for neurology, 20.8% hematology–oncology, 9.6% renal and 0.8% for rheumatology patients. Therapeutic plasma exchanges (n = 464; 94.3%) and therapeutic cytapheresis (n = 28; 6.7%) were performed in 113 and 12 patients, respectively. Majority of patients belonged to ASFA category I and II (n = 124; 99.2%). The overall response rate was 84%, with encouraging response in TTP (100%), aHUS (81.8%) and in neurological disorders (88.4%). Adverse events were reported in 52.8% of patients in 14.83% of procedures.

Conclusion

Our results of TPE in neurological disorders and in atypical hemolytic uremic syndrome are encouraging and it is a cost effective alternative to IvIg in neurological disorders. Currently, there is a need for establishment of an Indian apheresis registry to understand the scenario of TA across the country and in the expansion of appropriate and applicable indications for TA in our setting.     

Adverse reactions associated with mobile therapeutic apheresis:Analysis of 17,940 procedures

In order to evaluate the nature and frequency of adverse reactions associated with Therapeutic Apheresis (TA), database information from two large mobile apheresis services was analyzed. A total of 17,940 procedures performed on 3,583 patients were studied using an Access Database. Seventy percent (12,558) of the procedures were performed on a Fresenius AS104 blood cell separator and 30% (5,382) were performed on a COBE Spectra. The five most commonly treated diseases were Guillain‐Barre Syndrome (25%), thrombotic thrombocytopenic purpura (20%), myasthenia gravis (18%), the hyperviscosity syndrome (12%), and chronic inflammatory demyelinating polyneuropathy (9%). All patients received calcium gluconate supplement during the procedures. Cardiac monitoring was used during 80% of the procedures and blood pressure monitoring was used during all procedures. All procedures were supervised by a physician. Both apheresis services fully comply with the ASFA Guidelines for Therapeutic Apheresis Providers. Adverse reactions occurred in 3.9% of all procedures. The following adverse reactions were documented: reactions related to ACD toxicity (3%), vasovagal reactions (0.5%), vascular access related complications (0.15%), reactions related to FFP (0.12%), hepatitis B from FFP (0.06%), arrhythmias (0.01%), hemolysis due to inappropriate dilution of 25% albumin (0.01%), and one death (from underlying disease) during a TA procedure (0.006%). These data demonstrate that therapeutic apheresis is associated with a low rate of side effects when performed by well‐trained and certified nurses under the direction of experienced physicians, even in the diverse setting of large mobile therapeutic apheresis programs. J Clin Apheresis 16:130–133, 2001. © 2001 Wiley‐Liss, Inc.     

Plasma extraction rate and collection efficiency during therapeutic plasma exchange with Spectra Optia in comparison with Haemonetics MCS+

For therapeutic plasma exchange (TPE), continuous and intermittent flow separators are known to be efficient. This study was undertaken to compare the performances of the Spectra Optia, a continuous flow centrifugal apheresis system recently developed by CaridianBCT, with the Haemonetics Multicomponents System (MCS)+ apheresis system based on intermittent flow centrifugation. The primary objective of the study was to compare the time required to exchange one total plasma volume with both separators. The secondary objectives were to determine the plasma exchange efficiency, the plasma extraction rate, the percentage of target exchange volume achieved, and the loss of cellular components. The study involved prospectively paired comparison of 16 TPE on each device performed in patients with chronic diseases treated with TPE. The time required to exchange 1 total plasma volume was 182 ± 36 minutes for MCS+ procedures and 100 ± 20 minutes for the Spectra Optia procedures (P < 0.05, all results presented as mean ± standard deviation). A significantly higher plasma extraction rate was achieved (30.2 ± 4.3 vs 16.8 ± 3.4 mL/min, respectively, P < 0.05), and the plasma exchange efficiency was slightly better with the Spectra Optia compared with the MCS+ procedures (83.4 ± 7.0 vs 80.0 ± 8.5%, P < 0.05). The platelet loss was significantly lower with the Spectra Optia compared with the MCS+ procedures (1.6 ± 2.3 vs 7.5 ± 4.2%, respectively, P < 0.05), whereas the red blood cells loss was comparable. In conclusion, the Spectra Optia has significantly higher extraction rate and exchange efficiency than the MCS+ allowing to remove the same amount of plasma in less time, by processing less blood. It also removes significantly less platelets than the MCS+ separator.     

Therapeutic plasma exchange performed in parallel with extra corporeal membrane oxygenation for antibody mediated rejection after heart transplantation

We report on the feasibility, safety, and efficacy of performing therapeutic plasmapheresis (TPE) in parallel with extracorporeal membrane oxygenation (ECMO) to alleviate antibody mediated rejection (AMR) after heart transplantation. Two pediatric and one adult patient presented with severe congestive heart failure and respiratory distress after heart transplantation and required ECMO support. TPE was initiated to treat AMR while patients remained on ECMO. Each patient received three to five procedures either every day or every other day. One equivalent total plasma volume (TPV) was processed for each procedure (patient TPV + ECMO extracorporeal TPV). A total of 13 TPE procedures were performed with 12 procedures completed without complications or adverse events; one procedure was terminated before completion because of cardiac arrhythmia. Anti-HLA antibody titers decreased after TPE in all three patients. Ventricular function improved and ECMO was discontinued in 2 of 3 patients. Performing large volume TPE with a processed volume up to 2.5 times the patient's TPV is well tolerated in both pediatric (< or = 10 kg) and adult patients. TPE in parallel with ECMO is feasible, safe, and may be measurably effective at reducing anti-HLA antibodies and should be considered as part of the treatment for patients with early AMR after heart transplantation.     

United States thrombotic thrombocytopenic purpura apheresis study group (US TTP ASG): Multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) remains enigmatic from the perspective of its etiology, pathophysiology, and treatment. Once recognized, the accepted standard of care for TTP is daily therapeutic plasma exchange (TPE). However, the diversity in TPE treatment protocols has made comparisons of clinical research between institutions difficult. This study strived to assess the current practice of TPE in order to provide direction for prospective controlled clinical trials. Twenty large apheresis centers within the United States comprising the US TTP ASG responded to a survey to establish the current status of TPE in TTP. A retrospective analysis from data provided by 14 of 20 centers included 115 initial presentations of primary TTP with an overall mortality rate of 10% and relapse rate of 37%. The majority of deaths (58%) occurred within 48 hours of presentation. Variation in therapeutic targets (platelet count [plt] and serum LDH) and the number of plasma volumes exchanged per procedure did not affect the relapse rate. Initial plt and LDH were not predictive of mortality. Response, relapse, and mortality rates with the combination of 5% albumin for the initial 50% of TPE followed by plasma for the final 50% of TPE as replacement were comparable or possibly better than plasma-only replacement strategies. Forty percent of centers routinely used a TPE taper; however, there was no statistical difference in relapse rates comparing the taper and non-taper sub-groups. By controlling for adjunctive modalities such as steroids and anti-platelet agents, it is hoped that future prospective clinical trials may optimize the role of TPE in TTP, minimize patient exposure to blood products and procedures, shorten the clinical course of TTP, and reduce mortality. J. Clin. Apheresis 13:133–141, 1998. © 1998 Wiley-Liss, Inc.     

The mechanisms of rejection in solid organ transplantation

Organ transplantation represents the preferred treatment option for many patients in terminal organ failure. The half-life of transplanted organs, however, is still far from being satisfactory with the vast majority of the organs failing within the first two decades following transplantation. At this stage, it has become apparent that rejection (prevalently mediated by humoral events) remains the primary cause of graft loss after the first year. In this light, studies are underway to better comprehend the immune events underlying graft rejection and novel immunosuppressive strategies are being explored. In this context, therapeutic apheresis techniques, that include therapeutic plasma exchange (TPE), immunoadsorption (IA) and extracorporeal photochemotherapy (ECP), represent an important adjunct in the current immunosuppressive armamentarium. This article briefly reviews our current understanding of the immune process underlying rejection of a solid organ transplant and describes the principal areas of application of therapeutic apheresis techniques in transplantation.