Course Of Therapeutic Plasma Exchange Research Articles

Successful Use of Therapeutic Plasma Exchange Following Red Blood Cell Exchange for Severe Acute Chest Syndrome: A Single Institution Experience

Introduction: Severe acute chest syndrome (ACS) is a potentially fatal complication of sickle cell disease (SCD) that can progress to multiorgan failure. Treatment includes red blood cell (RBC) exchange to improve oxygenation and reduce vaso-occlusion by decreasing the proportion of hemoglobin (Hb) S. Patients with poor response to RBC exchange are at high risk for mortality. Therapeutic plasma exchange (TPE) may be beneficial in cases of severe organ dysfunction refractory to RBC exchange. TPE is postulated to remove pro-inflammatory cytokines, reduce circulating free hemoglobin, and decrease complement products that contributes to vaso-occlusion and inflammation. The use of TPE for severe ACS and multiorgan failure has been rarely described in adult patients and is even less commonly described for pediatric patients. Aim: To describe use of TPE for the management of severe ACS with multiorgan failure in two pediatric patients and one young-adult patient who did not respond to standard medical management with RBC exchange transfusion. Methods: Case reports Case 1: A six-year-old male with homozygous SCD (HbSS) and moderate persistent asthma was admitted for ACS. His course was complicated by hypoxemia requiring intubation, oliguria, and hypotension. On hospital day 3, he underwent RBC exchange with four units of RBCs. Despite decrease of Hb S to 15%, he remained hypoxic on high ventilatory support and developed acute respiratory distress syndrome. After multidisciplinary discussion, TPE was trialed in hopes of improving oxygenation and reversing multiorgan dysfunction. He underwent 3 TPEs, each with 1.5 total plasma volume (TPV) using 5% albumin (days 4, 5 and 7). After a single session of TPE, his oxygenation saturations improved to the 90s, and his ventilator support was weaned. He was extubated on day 8 and was discharged on day 13 in stable condition. Case 2: A sixteen-year-old male with HbSS, recurrent hyper-hemolytic syndrome, and sickle cell hepatopathy was admitted for medical optimization before scheduled cholecystectomy. His Hb was raised pre-operatively with erythropoietin, in lieu of RBC transfusion, due to history of severe refractory hyper-hemolysis with transfusions. He underwent uncomplicated cholecystectomy on hospital day 2. On day 3, he developed ACS, septic shock, and an exacerbation of known hepatopathy. He was intubated and underwent RBC exchange with 8 units of RBCs. His Hb S decreased to 20% but he had no improvement in clinical status. High-dose steroids and TPE were then trialed. The use of TPE was dual purposed to reduce inflammatory cytokines contributing to systemic dysfunction and to prevent hyper-hemolysis following exchange transfusion. He underwent 3 TPEs each with 1.5 TPV using 5% albumin for three days (days 5, 6, and 7). Throughout his course of TPE, he was extubated (day 6), weaned off pressor support (day 6), and his liver dysfunction began to improve (day 7). He was discharged home on day 16. Case 3: A thirty-five-year-old female with HbSS without chronic complications was transferred from an outside hospital where she presented 3 days prior with ACS and progressive neurologic deterioration with minimal responsiveness. Imaging revealed diffuse pulmonary infiltrates and extensive cerebral micro emboli consistent with fat embolism syndrome. She underwent RBC exchange on the day of arrival to our facility (hospital day 4) with 5 units of RBCs. Her Hb S decreased to 20% but she had no improvement in neurologic function. After multidisciplinary evaluation, TPE was trialed alongside high-dose steroids. She underwent 5 TPEs each with 1.0 TPV using 5% albumin (days 5, 6, 8, 9, and 12). Shortly after initiating TPE, she began recovering neurologically with eye-opening, response to noxious stimuli, and tracking (day 6). After 3 days of TPE, CRP fell from 21 to 5 and ESR from 49 to 23 (day 8). She followed commands on day 10 and was taken off oxygen on day 15. She was discharged to a rehabilitation facility on day 30 with significant improvements in mental status, cognition, and functional abilities. Conclusions: TPE for three to five days should be considered in patients with severe ACS and multiorgan failure with high risk of mortality when standard management fails. The early initiation of TPE likely contributed to the successful recoveries of these three cases. Further studies are needed to delineate the role of TPE in the management of acute complications of SCD.

Analysis of Prognosis and Therapeutic Effect of Patients with Thrombotic Thrombocytopenic Purpura

To summarize the features of clinical and laboratory parameters of thrombotic thrombocytopenic purpura (TTP), and to analyze the factors affecting the prognosis and therapeutic effect during the acute phase of the disease. The etiology, clinical features, laboratory parameters, treatment regimens and other data of 59 TTP patients admitted to Hunan Provincial People's Hospital were retrospectively analyzed. And the differences of each variable between the death group and the survival group were compared, the correlations between each variable and prognosis, as well as the therapeutic effect of the acute phase patients were analyzed. Among the 59 cases of TTP, one 4-year-old boy was inherited TTP, the other 58 cases were acquired TTP (39 cases were idiopathic TTP and 19 were secondary TTP), including 27 males and 31 females, with a median age of 54 (11-84) years old. 36 patients were tested for von Willebrand factor cleaving protease (ADAMTS13) activity, and 34 patients (94.44%) had decreased ADAMTS13 activity. There was a statistical difference in the activity of ADAMTS13 between idiopathic and secondary TTP patients (P<0.001). There were statistical differences in factors such as age (64 vs 51 years), ALT/AST ratio (0.61 vs 0.36), therapeutic plasma exchange (TPE) times (3 times vs 8 times), and TPE duration (3 d vs 9 d) between the death and survival groups. Multivariate analysis showed that total times of TPE (OR=5.175,95%CI: 1.169-22.914, P=0.030), ALT/AST ratio (OR=4.387, 95%CI: 1.019-18.891, P=0.047) were associated with mortality. COX regression analysis showed that degree of neuropsychiatric disorder (HR=0.200, 95%CI: 0.084-0.474, P<0.001), days from onset to initiation of TPE (HR=0.288, 95%CI: 0.114-0.726, P=0.008), treatment regimen (HR=0.336, 95%CI: 0.125-0.902, P=0.030) were associated with platelet recovery and therapeutic effect in the acute phase of the patients. TTP patients with high ALT/AST ratio have a higher mortality rate. Patients with enough times and full course of TPE have lower mortality rate. Poor therapeutic effect were found in TTP patients with severe neuropsychiatric disorders, delayed diagnosis and treatment, and who added rituximab when TPE was ineffective.

Therapeutic Plasma Exchange in a Patient With Acute Motor Axonal Neuropathy Subtype of Guillain-Barre Syndrome and Systemic Lupus Erythematosus

Objective To highlight treatment resistance of concurrent Guillain-Barre syndrome (GBS) and active systemic lupus erythematosus (SLE). Background Coincidence of SLE and GBS is an uncommon and complicated course of autoimmune disease. Treatment is further complicated by pregnancy exacerbation of SLE. Design/Methods We report a case of acute motor axonal neuropathy (AMAN) subtype of GBS in a young pregnant woman in her early 20s presenting with SLE. Patient was 10 weeks pregnant at presentation. Lumbar puncture study and electrical muscle stimulation (EMS) were consistent with acute motor axonal neuropathy subtype of GBS. Patient also had increased proteinuria and renal biopsy performed that was consistent with lupus nephritis. Despite treatment with IVIG and pulse dose corticosteroids, the patient had minimal neurological improvement with respiratory decline requiring intubation. Her pregnancy was terminated at this point and a course of therapeutic plasma exchange (TPE) was started followed by cyclophosphamide. Results The patient responded to the combination of therapy and had slow but gradual neurologic recovery as well as improvement of proteinuria. Conclusions Concurrent GBS and active SLE in the setting of pregnancy may be more treatment resistant, and combination therapy including TPE, immunosuppression, and termination of pregnancy may be indicated. For patients with concurrent GBS and SLE, especially axonal subtype of GBS and during pregnancy, TPE should be considered as a primary treatment option with respect to both efficacy and safety.

A clinical case of using therapeutic plasma exchange for the treatment of recurrent focal segmental glomerulosclerosis in a child after kidney transplantation

Background. Focal segmental glomerulosclerosis (FSGS) of the graft in kidney recipients is a rare and difficultto-diagnose post-kidney transplant complication, which can lead to graft loss and death of the recipient. A unified protocol is required for the treatment of this disease.Materials and methods. A 15-year-old female patient C. diagnosed with stage 5 chronic kidney disease as a result of steroid-resistant nephrotic syndrome with hematuria underwent a living related-donor kidney transplantation. On the third day after the operation, laboratory and imaging data showed kidney graft dysfunction. Patient examinations established the cause of the graft dysfunction – idiopathic nephrotic syndrome in FSGS.Results. For the treatment of recurrent FSGS, the patient had her immunosuppressive therapy converted from tacrolimus to cyclosporin A, and received two 500 mg rituximab injections. Ten sessions of therapeutic plasma exchange (Plasauto Sigma) were performed to remove antibodies to podocytes. During the therapy, diuresis was restored, creatinine and urea levels decreased. Six months after the kidney transplant, graft function was fully restored. Conclusion. The absence of recurrent FSGS within six months during a single course of therapeutic plasma exchange with its subsequent cancellation after restoration of graft function allows to recommend the developed method for the treatment of FSGS in pediatric patients after kidney transplantation.

Retrospective analysis of outcomes in patients with acute hypertriglyceridemic pancreatitis treated without therapeutic plasma exchange.

Therapeutic plasma exchange (TPE) is often used to decrease serum triglyceride levels in hypertriglyceridemic pancreatitis (HTGP), although there is a lack of high-quality data directly attributing improved clinical outcomes to TPE. There are currently no large studies evaluating the treatment of HTGP without TPE. This study retrospectively analyzes clinical and laboratory outcomes of 115 encounters at Massachusetts General Hospital (MGH) wherein a HTGP patient was treated without TPE and compares these outcomes to those of HTGP patients in the literature treated with TPE. After management without TPE, the median reduction in serum triglycerides was 48% (IQR 29%-63%) on day one and 74% (IQR 60%-84%) on day two in 115 episodes of acute HTGP. The reductions were comparable to those reported in several large published case series after a course of TPE (65.8% to 81% reduction). In 25 episodes among 24 patients, treatment included admission to an intensive care unit. There was no significant difference in mortality or rates of local complication, mechanical ventilation, or use of vasoactive medication or renal replacement therapy between this ICU subset and published cohorts (all P > .05). HTGP patients who do not receive TPE do not experience inferior outcomes compared to patients in the literature treated with TPE. The added value of TPE in HTGP, if any exists, needs to be demonstrated in controlled trials.

Acquired factor XIII deficiency in patients under therapeutic plasma exchange: A poorly explored etiology.

Factor XIII (FXIII) deficiency may cause bleeding under certain clinical circumstances. Therapeutic plasma exchange (TPE) may lead to a transient deficiency. To describe the clinical evolution of patients with acquired FXIII deficiency secondary to TPE. We respectively studied a cohort of consecutive patients from 2014 to 2019 who were treated with TPE with FXIII levels <50%. The FXIII was measured after the start of the TPE course, on days between the TPE sessions, due to suspected acquired deficiency. All TPE were performed using continuous flow cell separator. In all cases, the initial replacement fluid applied was albumin. Apheresis procedures were held at 24to 48 hours intervals. Eighteen patients were included, 13 of them were recipients of kidney transplants. The main TPE prescription was humoral rejection. Median FXIII at diagnosis (measured on days between sessions of the TPE course) was 19%(IQR17-25). The median of apheresis procedures before measurement of FXIII was 3(IQR2-4). Among the total cohort, 10 patients suffered hemorrhages. None of the patients without history of kidney transplants had bleeding (n = 5), however, 10/13 with kidney transplants did. Five kidney transplant patients received therapy with FXIII concentrate because of life-threatening bleeding. In all cases, the bleeding stopped within the first 24 hours. All patients had their FXIII levels measured again after finishing the TPE course, with normal results. TPE is an under-diagnosed cause of acquired FXIII deficiency since routine coagulation tests remain unaltered. It might cause major bleeding, particularly in patients with a recent history of surgery like kidney transplants.

Therapeutic plasma exchange may adjust IL-6 and TGF-β signals in relapsed MS patients peripheral blood.

Effects of therapeutic plasma exchange (TPE) on immune cells and their cytokine production in MS, are unknown. Since interleukine-6 and tumor growth factor-β have critical roles in MS immunopathogenesis, the impacts of TPE on the expression of these cytokines and their receptors on the surface of CD4+ T lymphocytes, were investigated. Blood cells were obtained from 30 Relapsing-Remitting (RR) MS patients, before and after a complete TPE course. Cytokines mRNA and their receptor expression on the CD4+ T cells surface were assessed using real-time PCR and flowcytometry, respectively. TPE reduced symptom severity (P = .01) and the relief was higher in males than in females (P = .039). TPE also increased TGF-β mRNA and decreased IL-6 receptor expressing cells frequency (P = .009 and P = .028, respectively). Moreover, the frequency of CD4+IL6R+ T cells was positively correlated with disease severity (P = .001). TPE impacts simultaneously on the TGF-β mRNA and IL-6 receptor expression, and this may be a mechanism of improvement in MS relapse symptoms induced by the TPE.

Utility and safety of plasma exchange in paediatric neuroimmune disorders

Our aim was to ascertain the indications, side effects, and outcomes in children receiving therapeutic plasma exchange (TPE) for neurological disorders. Medical records were retrospectively reviewed for 58 consecutive children (age ≤16y) undergoing 67 courses of TPE across four tertiary centres. Patient characteristics, treatment schedules, complications, and outcomes were analysed. Median age at initiation of TPE was 9years (range 1-15y). Indications included peripheral nervous system (PNS; n=18) and central nervous system (CNS; n=40) disorders. Courses comprised a median six exchanges (range 2-179) over 8days (range 3-466). Forty-two out of 58 (73%) children were severely disabled (bedridden) at initiation and 24 out of 58 (41%) were admitted to intensive care units. Treating clinicians' impression of response was positive in 16 out of 18 of those with PNS disorders versus 22 out of 40 with CNS disorders (p=0.016). Improvements in disability (modified Rankin Scale) occurred in 13 out of 58 (22%) children by completion of TPE (p=0.003). Complications occurred in 40 out of 67 (60%) courses, of which 16 out of 67 (24%) were line related. Potentially life-threatening complications occurred in 2 out of 67 (3%) courses. This cohort study provides safety and efficacy information for clinicians and families and a basis for future prospective studies. Disability scores for severe neuroimmune disorders remained stable or improved during therapeutic plasma exchange treatment. Complications occurred frequently but were typically mild and correctable.

Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy: An Institutional Experience

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplant (HSCT) that causes severe multiorgan injury. The kidneys are almost universally affected. There is no proven therapy, but therapeutic plasma exchange (TPE) is commonly used to treat TA-TMA at Texas Children's Hospital (TCH). To date, there have been no studies assessing the long-term efficacy of TPE in preventing the development of chronic kidney disease (CKD) in TA-TMA patients. In this study we retrospectively analyzed the incidence of CKD in TA-TMA pediatric patients treated with TPE to determine if this treatment modality improves renal morbidity. We reviewed records between January 2007 and June 2017 of pediatric HSCT patients diagnosed with TA-TMA, identified through an internal database maintained at TCH. To be included patients must have completed a course of TPE per the “TPE in TA-TMA” institutional protocol at TCH. CKD was defined as kidney damage for at least 3 months and stratified into stages 1 through 5 according to estimated glomerular filtration rate. Stages 4 and 5 were considered “severe CKD.” In the 10-year timeframe 15 patients with TA-TMA completed a course of TPE per our institutional protocol and were subsequently followed for a median of 963 days. Fourteen patients developed CKD, and 5 of these 14 patients developed severe CKD. The cumulative incidence of severe CKD development was 33% (95% confidence interval. 11% to 57%). 6 patients required dialysis, and 2 patients received a renal transplant. 5 patients received eculizumab in addition to TPE. In our patients a TPE course of at least 7 weeks (and up to 25 weeks) was not effective in the prevention of CKD. Our data indicate a need for alternative therapeutic measures to prevent the development of CKD in TA-TMA patients.

Personalized treatment with immunoadsorption and intravenous immunoglobulin in a case of severe Rh alloimmunization during pregnancy unresponsive to plasma – exchange

IntroductionDespite prophylaxis, a small proportion of RhD-negative women may develop anti-D antibodies after a sensitizing event occurring during pregnancy or delivery of a D-positive baby. Intrauterine transfusion (IUT) is the treatment of choice in case of fetal anemia, but it cannot be performed early during pregnancy. Combined treatment with therapeutic plasma-exchange (TPE) and intravenous immunoglobulin (IVIG) can avoid or delay IUT. Immunoadsorption (IA) could represent a more effective treatment in selected cases. Case reportWe report a D-negative female with a history of induced abortion and hydrops fetalis, referred at 8 weeks of gestation with a high anti-D titer. Despite implementing a TPE-IVIG protocol, the patient experienced a spontaneous abortion. At the beginning of her fourth pregnancy, only after a partially effective intensive TPE course, cycles of IA-IVIG were performed. Despite a suboptimal response on the anti-D titer, Doppler ultrasonographic measurements of the fetal middle cerebral artery peak systolic velocity first showed evidence of anemia at 30 weeks of gestation and a IUT was required. After the IUT, anemia persisted with a subsequent dramatic rise in titer, requiring an emergent cesarean section. The infant subsequently underwent successful treatment with IVIG, phototherapy and exchange transfusion and was discharged 7 weeks later without neurological deficits. DiscussionThe treatment of high titer anti-D antibodies during pregnancy may require a multidisciplinary approach with utilization of different apheresis strategies in order to have a successful pregnancy outcome.

A Novel PF4-Dependent P-Selectin Expression Assay (PEA) Facilitates Early Detection of Pathogenic HIT Antibodies: Implications for Diagnosis and Treatment of HIT

The PF4-dependent P-Selectin Expression Assay (PEA) is a novel assay for diagnosis of heparin-induced thrombocytopenia (HIT) which, in preliminary testing, demonstrates higher diagnostic accuracy than the "gold standard" serotonin release assay (SRA) (Padmanabhan et al. Chest, 2016 epub). Here, we describe two cases of severe thrombotic HIT in which the PEA detected pathogenic HIT antibodies (abs) before the SRA tested positive, and in one case, earlier than the highly sensitive PF4 ELISA. These findings have implications for diagnosis and monitoring of the response to therapy in HIT.Patient 1, a 67 yr old woman was admitted for treatment of a Bochdalek hernia and was started on unfractionated heparin (UFH). Her course was complicated by a declining platelet count and on the eighth day of admission PF4 ELISA and SRA tests were strongly positive (Fig 1A). Vascular imaging demonstrated venous thrombosis in both upper and lower extremities. Pre- and post-diagnosis patient samples were tested in the PF4 ELISA, SRA and PEA (Fig 1A). The PEA was positive at 152 hrs (~6 days) post-heparin exposure (69% expression), but the PF4 ELISA was only weakly positive (OD 0.67) and the SRA was negative (0%) at a time when the platelet count was 52% of baseline (Fig 1A). The SRA was still negative (18%) 16 hours later (168 hrs). Thirty hours after the first positive PEA test result, the SRA became positive (100% release). The patient's condition was then further complicated by sepsis-associated multisystem organ failure (MSOF) and therapeutic plasma exchange (TPE) was instituted. TPE treatment led to a rapid reduction in the SRA but only a gradual decline in PEA and ELISA test results (Fig 1B), in line with gradual improvement in platelet counts. Dissociation between SRA and PF4 ELISA test results following TPE has been described previously (Blood. 2015;125:195-8). In our patient, a PEA-SRA dissociation was also observed. Early in this patient's course, PEA-positive/SRA-negative abs were clearly "pathogenic," causing a significant decrease in platelet counts. Thus, it is plausible that PEA-positive/SRA-negative abs detected during the course of TPE were also "pathogenic". PEA results during the course of TPE appeared to correlate better with clinical status in light of the gradual improvement in platelet counts. Unfortunately, the patient expired after the 4th TPE secondary to complications of MSOF.Patient 2, a 57 yr old man was admitted for a creation of a thigh flap in preparation for knee replacement. Postoperatively, the flap became pale with poor pulses and UFH was started. On day 5 platelets dropped 25% from baseline and PF4 ELISA and SRA were both negative (Fig 1C). A strong suspicion of HIT prompted repeat testing on day 6, and yielded positive SRA (79%) and PF4 ELISA (2.8 OD) test results. Notably, the PEA was positive (74%) on Day 5 when both PF4 ELISA and SRA were negative. All tests remained strongly positive through day 12. Thrombocytopenia persisted (Fig 1C) and extensive venous thrombosis of the right upper extremity developed on day 15. The patient was transitioned to Coumadin after platelet recovery and discharged on Day 30.Previous studies indicate that the PEA is at least as accurate as the SRA for detection of pathogenic abs (Padmanabhan et al Thromb Haemost. 2015;114:1322-3, Padmanabhan et al. Chest, 2016 epub). Experience with these two cases suggests that the PEA may in some cases detect pathogenic antibodies before the SRA becomes positive and may be superior to the SRA for monitoring response to treatment. Because of its technical simplicity, the PEA has the potential to be performed on demand, rather than through a referral laboratory, facilitating early diagnosis and treatment. [Display omitted] DisclosuresPadmanabhan:Fenwal (Fresenius Kabi): Research Funding; Schlesinger & Associates: Consultancy, Honoraria; LEK Consulting: Consultancy, Honoraria; Mallinckrodt Pharmaceuticals: Consultancy, Honoraria; Terumo BCT: Consultancy, Honoraria; Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591. Jones:Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591. Bougie:Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591. Aster:Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591.

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1–4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60–70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

Report of the ASFA apheresis registry on muscle specific kinase antibody positive myasthenia gravis.

Anti-muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti-acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. The study collected detailed de-identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 - 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty-one percent of patients responded poorly with minimal recovery. Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor-responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5-11, 2017. © 2016 Wiley Periodicals, Inc.

Therapeutic plasma exchange in neurology: 2012

In treating neuroimmunological diseases, neurologists have a number of different drugs to choose from ranging from corticosteroids to IVIg to more specific cell based therapies, the latter most frequently from the world of oncology. In some diseases, therapeutic plasma exchange, a procedure rather than a drug, is used. The most obvious advantage of therapeutic plasma exchange is the usually rapid onset of action presumably due to removal of pathogenic auto-antibodies. In some diseases, a single course of therapeutic plasma exchange is used while in others prolonged treatment with therapeutic plasma exchange is used. This article will review the use of therapeutic plasma exchange in neurology and will draw heavily upon recent consensus statements from the American Society for Apheresis and the American Academy of Neurology and by Cochrane reviews.

Does early initiation of therapeutic plasma exchange improve outcome in pediatric stem cell transplant–associated thrombotic microangiopathy?

The use of therapeutic plasma exchange (TPE) in hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is controversial because the exact mechanism of injury in TA-TMA is not yet understood. The study objective was to retrospectively review the outcome of children receiving TPE for TA-TMA at our institution. We hypothesized that patients initiating TPE earlier in their disease course would receive a greater benefit than those starting later, regardless of the therapeutic mechanism. We identified 10 consecutive pediatric patients with TA-TMA treated with TPE. Nine of these patients showed normalization of the laboratory variables associated with microangiopathy during their TPE course, but only five patients recovered renal function and survived TA-TMA. The five survivors started TPE a median of 17 days (range, 4-25 days) after TA-TMA diagnosis while the five patients who died started TPE a median of 32 days (range, 17-73 days) after TA-TMA was diagnosed. Three of the five survivors had multiorgan failure at TA-TMA diagnosis and completely recovered with early institution of TPE. These three survivors were able to discontinue renal replacement therapy, and all achieved a normal posttreatment creatinine. The five patients with later institution of TPE progressed to end-stage renal disease and all died. There were no serious TPE-related complications in either group. This is the first report evaluating TPE response in regard to procedure initiation time after TA-TMA diagnosis. Our data suggests that early initiation of TPE might be beneficial even in patients with multiorgan failure due to TA-TMA.

SLE with diffuse alveolar hemorrhage, microangiopathic hemolytic anemia and acute renal failure

In SLE patients with diffuse alveolar hemorrhage (DAH) and acute renal failure (ARF), the most common associated renal injury is proliferative lupus nephritis. We report a case of a young SLE patient with DAH and ARF who was successfully treated with a course of therapeutic plasma exchange (TPE) plus pulse IV cyclophosphamide. Kidney biopsy revealed an alternative diagnosis.

Therapeutic plasma exchange in Streptococcus pneumoniae‐associated hemolytic uremic syndrome: A case report

Streptococcus pneumoniae-associated hemolytic uremic syndrome (pHUS) is an atypical form of HUS associated with microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Although less common than diarrhea-associated HUS, incidence appears to be increasing. We report a case of a child with pHUS who underwent a course of therapeutic plasma exchange (TPE) and had complete recovery. This report adds to the existing literature supporting TPE in cases of pHUS.

Polyclonal Antibody-Induced Serum Sickness in Renal Transplant Recipients: Treatment with Therapeutic Plasma Exchange

Serum sickness is an immune-complex mediated illness that frequently occurs in patients after polyclonal antibody therapy (ATGAM or thymoglobulin). Serum sickness presents with significant morbidity but is self-limited and resolves with prolonged steroid therapy. We present five renal transplant patients who developed serum sickness after polyclonal antibody treatment with severe symptoms that persisted after being started on systemic steroids. These patients underwent one or two courses of therapeutic plasma exchange (TPE) with subsequent complete resolution of their symptoms. Renal transplant recipients with serum sickness after polyclonal antibody therapy may benefit from TPE by accelerating their time to recovery and thereby reducing overall morbidity.

Retrospective study of plasma exchange in children with systemic lupus erythematosus.

A retrospective review of patients was conducted to evaluate the short-term effect of therapeutic plasma exchange (TPE) in children with active systemic lupus erythematosus (SLE). Between April 1984 and March 2003, 22 children underwent 112 TPE sessions. The median number of daily, double-volume sessions was 6 (range 1-16). Plasma exchange was performed by centrifugation, using 4.5% albumin with fresh-frozen plasma as required. All children were receiving standard immunosuppressive therapy. The predominant clinical features that led to TPE were categorised into systems and outcome was evaluated according to clinical improvement or lack of it. There was benefit for central nervous system and pulmonary manifestations (10 cases, 11 episodes). Of 8 children treated for renal manifestations, 6 achieved good outcomes. Two children became dialysis dependent despite treatment; however, both had been successfully treated with TPE before. Five children received more than one course of TPE. No child died during the procedure and major complications were few. Our data show that TPE can be used as adjunctive therapy in childhood SLE with few complications. Outcome is difficult to measure but in our experience, during the acute phase of illness, TPE appears to be of benefit.

Therapeutic plasma exchange in recurrent focal segmental glomerulosclerosis following transplantation.

Focal segmental glomerulosclerosis (FSGS) recurs in 30% of renal allograft transplants with graft loss in half of the cases. A humoral factor may be implicated. We report on the use of therapeutic plasma exchange (TPE) in 11 patients with recurrent FSGS post transplantation. Medical records from 1989-2000 were reviewed for 11 adults transplanted for biopsy proven FSGS. Ten patients developed proteinuria (x: 6.1 g; range: 3-40 g/24 h) within 2 months of transplantation. In 1 patient, proteinuria (4 g) occurred 2 years post transplantation. Biopsy in six patients revealed early recurrent FSGS, while in five, suspected recurrence was based on clinical findings. Each patient received 5-11 TPEs (x: 6) with the COBE Spectra, daily or on alternate days with 2.5-3.5 L 5% albumin as the replacement fluid. In four, FFP was included because of coagulopathy. All received immunosuppression (IS) during and after TPE. A persistent drop in 24 h urine protein (U.P.) was observed in 10/11 patients. Seven had >70% drop in 24 h U.P. following the course of TPE, while three had a reduction of 45-50%. No change occurred in 1 patient. Follow-up (9 months-5 years) of seven patients has shown a persistent U.P. of <1 g with successful allograft survival. In these patients, TPE appeared effective in early recurrent FSGS. The decrease in U.P. may result from combined TPE and IS. Although the disease is designated in category III by the ASFA, TPE should be considered early when FSGS recurrence is established.