Initiation Of Therapeutic Plasma Exchange Research Articles

A Life Saving Exchange: A Case of Severe Direct Hyperbilirubinemia And Liver Failure in Leptospirosis Successfully Treated with Plasma Exchange

Leptospirosis is an infection with multiorgan involvement and a high mortality rate. Extreme hyperbilirubinemia in leptospirosis has been reported to exert multiple cellular toxic effects on kidney and liver cells. We describe a young man with leptospirosis who had extreme hyperbilirubinemia, acute liver injury, coagulopathy, hepatic encephalopathy, and pulmonary haemorrhages. Early initiation of therapeutic plasma exchange (PEX) dramatically improved patient’s clinical and biochemical parameters. We conclude that, in addition to the mortality benefit provided by PEX in severe pulmonary hemorrhage syndrome in leptospirosis, PEX is also beneficial in reducing systemic toxic insults of hyperbilirubinemia.

Plasma Exchange in Pediatric Neurology Patients: A Single-Center Experience.

Therapeutic plasma exchange (TPE) is a procedure involving the filtration of a patient's plasma to eliminate pathogenic components or address deficiencies. This technique finds varied indications in the pediatric age group, particularly in neuroinflammatory diseases. The objective of this study is to delve into our local experience with TPE, focusing on indications, outcomes, and complications among children with neurological diseases at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Conducted at the pediatric department of KAUH in Jeddah from November 2008 to July 2023, this retrospective cohort study examined 15 patients, revealing a notable male predominance with 12 male patients (80%) and three female patients (20%). About two-thirds of patients exhibited an average illness severity, with a Glasgow Coma Scale (GCS) score of 10.7 and anExpanded Disability Status Scale (EDSS) score of 4.8. The median length of hospital stay was 23 days, and in the pediatric intensive care unit (PICU), it was 8.5 days. Presenting symptoms included limb weakness (n = 6), loss of consciousness (n = 3), dysphagia (n = 3), photophobia (n = 1), and ascending paralysis (n = 1). The TPE was performed for Guillain-Barré syndrome (GBS) (n = 7), myasthenia gravis (MG) (n = 3), transverse myelitis (TM) (n = 2), neuromyelitis optica (NMO) (n = 2), and systemic lupus erythematosus (SLE) cerebritis (n = 1). Twelve patients were admitted to the PICU, and mechanical ventilation was required for 10 patients. In magnetic resonance imaging (MRI) findings, abnormalities were observed in 10 cases, while the remaining five either had normal results or did not undergo MRI. Most patients required five sessions of TPE (n = 7). The median age at the initiation of TPE was 13 years. Twelve patients improved with TPE treatment, while three did not. Complications observed during and following TPE included fever (n = 5), electrolyte disturbance (n = 5), hypotension (n = 3), hypocalcemia (n = 2), bradycardia (n = 2), vomiting (n = 1), tachycardia (n = 1), eye rash (n = 1), infection (n = 1), and bleeding originating from the TPE procedure site (n = 1). In conclusion, our study underscores the significance of TPE as a therapeutic modality, emphasizing the imperative for ongoing research to fully exploit its potential across diverse medical contexts for enhancing patient care. Our findings, consistent with prior research, reveal plasma exchange's (PLEX's) wide-ranging applications and complications in neurological disorders.

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.

Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Hereditary or congenital TTP (cTTP) is caused by ADAMTS13 gene mutations. In acquired or immune TTP (iTTP), ADAMTS13 activity is reduced by anti-ADAMTS13 autoantibodies. TTP is characterized by thrombocytopenia, hemolytic anemia, fever, renal dysfunction, and neuropsychiatric symptoms. Therapeutic plasma exchange (TPE) and immunosuppressive therapy are the mainstays of treatment. As untreated TTP has a high mortality rate, immediate initiation of TPE is recommended when TTP is suspected. Conventionally, corticosteroids have been used for immunosuppressive therapy. Current drug therapies include rituximab, an anti-CD20 antibody that is effective in newly diagnosed cases and refractory cases, as well as for relapse prevention, and caplacizumab, an anti- von Willebrand factor (VWF) nanobody that inhibits the binding of platelets to VWF and prevents microthrombi formation. Recombinant human ADAMTS13 is a promising treatment for cTTP. Although these therapeutic advances have improved the outcomes of TTP, early diagnosis and prompt initiation of appropriate therapy are necessary to achieve these outcomes.

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.

Comparison of absolute immature platelet count to the PLASMIC score at presentation in predicting ADAMTS13 deficiency in suspected thrombotic thrombocytopenic purpura

IntroductionThrombotic thrombocytopenic purpura (TTP) demands rapid initiation of therapeutic plasma exchange to avoid severe complications associated with it. ADAMTS13 activity <10% defines TTP, however, this is a send-out test at most institutions. We have previously reported our experience looking at absolute immature platelet counts (A-IPC) in TTP patients. Thus, we compared A-IPC on admission to the PLASMIC score to predict ADAMTS13 deficiency. Materials and methodsOf seventy-two patients identified, 52 met inclusion criteria. All patients were suspected of new-onset TTP and had A-IPC on admission. Of these patients, 25/52 were later shown to have ADAMTS13 <10%, defined as TTP group, and 27/52 had ADAMTS13 >10% and are henceforth classified as non-TTP. ResultsPatients with TTP were found to have A-IPC below reference range (<1.5 × 109/L) and responded to therapy as shown by fold-increases in A-IPC (p < 0.0001), neither seen in non-TTP patients. A-IPC had a significant correlation with ADAMTS13 deficiency (p = 0.0001) with high sensitivity, specificity, positive and negative predictive values. Comparison of A-IPC to PLASMIC score indicated that the former identified all TTP patients compared to PLASMIC score even in patients obtaining scores of 4 and 5. Finally, Receiver Operating Characteristic curves showed A-IPC had area under the curve of 0.986. ConclusionsA-IPC below reference range and A-IPC fold-increases were only observed in TTP patients. There was strong association between A-IPC and ADAMTS13 deficiency and A-IPC predicted patients with ADAMTS13 deficiency. Future larger studies are needed to determine ways to apply findings in suspected TTP patients.

Therapeutic plasma exchange for multiorgan dysfunction among critically ill pediatric patients with leukemia: A single-institutional experience.

Therapeutic plasma exchange (TPE) has well-documented applications in the adult population, outlined by the American Society for Apheresis (ASFA) 2019 guidelines. Limited data exist regarding the use of TPE in critically ill pediatric patients; however, these reports rarely include patients with oncological diseases. We highlight the use of TPE in the acute management of seven pediatric patients with leukemia treated at Children's Mercy Hospital ICU from 2015 to 2020, including TPE specifications, baseline and interval laboratory evaluation, and outcome measures. Analysis compared those who did (n=4) and did not (n=3) survive 30 days post-TPE. Multiorgan failure (MOF) prompted the initiation of TPE in 85.7% of patients, 57.1% of whom were also diagnosed with hemophagocytic lymphohistiocytosis (HLH). Baseline laboratory evaluations prior to initiation of TPE were similar between the two groups. With subsequent TPE treatments, C-reactive protein (CRP) and lactic acid decreased. CRP and lactic acid following the last TPE treatment were significantly higher for those deceased 30 days post-TPE (P = .023 and .031, respectively). No TPE-associated adverse events necessitated discontinuation of TPE treatment. Several surviving patients required chemotherapy dose reductions or alterations. Our cohort demonstrated MOF and HLH consistently as indications for TPE, currently ASFA category III indications (optimal role of apheresis is not yet established). Recognition of this treatment modality earlier in the clinical course for critically ill oncological patients may lead to the development of formal protocols that may result in earlier initiation of TPE and improved outcomes.

Therapeutic plasma exchange followed by convalescent plasma transfusion in severe and critically ill COVID-19 patients: A single centre non-randomized controlled trial.

Therapeutic plasma exchange (TPE) has been proposed as a rescue therapy in critically ill COVID-19 patients. The aim of the present study was to determine whether combining TPE with convalescent plasma (CVP) transfusion early in the intensive care unit (ICU) stay improves survival among this heterogeneous population. The primary endpoint was survival at 30 days. Secondary endpoints included assessing the evolution of biomarkers, such as the partial pressure of arterial oxygen to fractional inspired oxygen ratio, and C reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin levels at the 7-day follow-up. This single centre, prospective, non-randomized controlled trial was conducted in an 8-bed COVID-19 ICU and included patients with severe COVID-19 pneumonia requiring intensive care treatment. A total of 19 patients were treated by performing TPE followed by CVP transfusion, in addition to standard treatment, while for another 19 patients, only standard treatment according to hospital protocols was used. TPE was initiated during the first 24 h after ICU admission, followed immediately by transfusion of CVP. Survival at 30 days was 47.37% in the TPE CVP group and 26.32% in the control group (P=0.002). Patients in the TPE CVP group also showed better oxygenation and a reduction in inflammation, with decreased CRP, LDH and ferritin levels compared with those in the control group. Overall, the study indicated that early initiation of TPE followed by CVP transfusion may be a valid rescue therapy in severe and critically ill COVID-19 patients, with a statistically significant survival benefit, improved oxygenation and a reduction in inflammatory markers. The trial was registered in the ClinicalTrials.gov database (trial registration number: NCT04973488) on July 22, 2021 (retrospectively registered).

Deleterious neurological impact of diagnostic delay in immune-mediated thrombotic thrombocytopenic purpura.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic microangiopathy requiring urgent therapeutic plasma exchange (TPE). However, the exact impact of a slight delay in TPE initiation on the subsequent patients' outcome is still controversial. We aimed to study the frequency, short-term neurological consequences, and determinants of diagnostic delay in iTTP. We conducted a retrospective monocentric study including patients with a first acute episode of iTTP (2005-2020) classified into 2 groups: delayed (>24h from first hospital visit, group 1) and immediate diagnosis (≤24h, group 2). Among 42 evaluated patients, 38 were included. Eighteen cases (47%) had a delayed diagnosis (median: 5 days). The main misdiagnosis was immune thrombocytopenia (67%). The mortality rate was 5% (1 death in each group). Neurological events (stroke/TIA, seizure, altered mental status) occurred in 67% vs 30% patients in group 1 and 2, respectively (p = 0.04). Two patients in group 1 exhibited neurological sequelae. The hospital length of stay was longer in group 1 (p = 0.02). At the first hospital evaluation, potential alternative causes of thrombocytopenia were more prevalent in group 1 (33% vs 5%, p = 0.04). Anemia was less frequent in group 1 (67% vs 95%, p = 0.04). All patients had undetectable haptoglobin levels. By contrast, 26% of schistocytes counts were <1%, mostly in group 1 (62% vs 11%, p = 0.01). Diagnostic delay is highly prevalent in iTTP, with a significant impact on short-term neurological outcome. In patients with profound thrombocytopenia, the thorough search for signs of incipient organ dysfunction, systematic hemolysis workup, and proper interpretation of schistocytes count are the key elements of early diagnosis of TTP.

Evaluating Patterns in ADAMTS13 Testing and Time to Plasma Exchange Initiation for Suspected Thrombotic Thrombocytopenic Purpura at a County Hospital

Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease with a mortality 10-20% despite emergent therapeutic plasma exchange (TPE). The distinguishing aspect of iTTP from other thrombotic microangiopathies is a severe deficiency of ADAMTS13 (<10% activity) with laboratory evaluation of ADAMTS13 activity often requiring hours to days; thus, it is not useful for determining whether plasma exchange for TTP should be initiated. Guidelines also recommend TPE initiation within 4-8 hours (Scully 2012). There is limited literature regarding utilization of ADAMTS13 testing in the hospital, and we sought to understand ordering patterns in various clinical contexts, which services ordered ADAMTS13 activity, and if TPE initiation was timely.Methods: Parkland Health and Hospital System records were reviewed ADAMTS13 activity tests (n = 361) from January 2019 to March 2021, excluding patients with known iTTP and/or outpatient tests; resulting in a final cohort of 42 patients with inpatient ADAMTS13 activity tests for suspected iTTP. Suspicion for iTTP-time zero for our time to TPE analysis-was determined by the time that the ADAMTS13 order was placed. Hematology consultation time was based on when the order was placed by the provider. The initiation of TPE, as documented by the apheresis team, was the end-time for the time to TPE calculation. Thus, time to TPE was the time elapsed between the electronic ADAMTS13 order being placed and TPE being initiated.Results: The median patient age was 43 years with 36% Black patients and 50% Hispanic. Hematology service consultation occurred in 95% of cases, although only 79% of hematology consultations occurred before ADAMTS13 activity orders were placed (Table 1). The most common services to order an ADAMTS13 activity prior to hematology consultation were obstetrics and gynecology (2/2, 100%), neurology (1/1, 100%), and medical intensive care (5/14, 36%) with 88% of these tests being placed for patients with a PLASMIC score ≤ 4. None of these patients were diagnosed with iTTP. Using a PLASMIC score ≥6 as a diagnostic test for iTTP, the sensitivity was 50%, specificity 84%, positive predictive value 20%, and negative predictive value was 94%.A subgroup analysis of patients empirically treated for iTTP (n = 7) demonstrated a wide variation in the time from ADAMTS13 activity orders being placed to initiation of TPE, ranging from 4 hours 44 minutes to 3 days 14 hours (Table 2). Only one patient (without a pre-existing central line) received empiric TPE in under 6 hours (5 hours and 20 minutes). One patient had an ADAMTS13 activity that resulted with a critical ADAMTS13 deficiency and was initiated on TPE; this level was re-analyzed, found to be spurious, and the TPE was ceased immediately. No patients received empiric plasma transfusion.Discussion: At our county, public hospital, 95% of cases with suspected iTTP involved hematology consultation during their evaluation, but the most common situations where hematology was not involved at all or was involved late were due to non-internal medicine services, identifying areas for focused educational interventions. The PLASMIC score demonstrated insufficient sensitivity (50%) to confidently exclude iTTP, suggesting that it is an inadequate risk stratification tool for our specific patient population. This may be due to differences between our patient population (with a median age of 43 and 12% white patients) and the derivation cohort for the PLASMIC score (with a median age of 51 and 77% white patients; Bendapudi 2017). The finding that only one patient without a pre-existing central line received TPE in ≤6 hours suggests that there is room for quality improvement interventions to hasten time to treatment. This initial study has led to the development of systemic, hospital-wide electronic medical record order set changes combined with educational interventions which will be evaluated prospectively for its impact on iTTP diagnosis and treatment. Broadly, this study re-demonstrates that the evaluation, diagnosis, coordination, and treatment of iTTP is often logistically challenging. Promoting earlier hematology consultation and optimizing EMR interventions is likely to facilitate appropriate ADAMTS13 testing, expedite results, and help coordinate the initiation of TPE in patients with suspected iTTP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment Outcome and Efficacy of Therapeutic Plasma Exchange for Transplant-Associated Thrombotic Microangiopathy in a Real-World Large Cohort Study

IntroductionTransplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with mortality over 80%. Effective management of TA-TMA is hampered by obscure pathogenesis and delayed diagnosis. There are no well-acknowledged therapeutic strategies for TA-TMA. TA-TMA-directed therapy includes therapeutic plasma exchange (TPE), eculizumab, rituximab, and defibrotide. The efficacy and outcome of TPE for the treatment of TA-TMA remain controversial. To our knowledge, this is the largest cohort to date of patients treated with TPE for TA-TMA after allo-HSCT. We aimed to identify predictors of response and mortality in patients with TA-TMA who received TPE, and to recognize patients who will benefit from TPE management.MethodsA total of 6241 subjects who underwent allo-HSCT were performed at Peking University People's Hospital from January 2010 to December 2019, of whom 538 patients were diagnosed with TA-TMA, with a cumulative incidence of 8.6%. Among them, 82 consecutive critically ill TA-TMA patients received TPE. TA-TMA was diagnosed using the criteria proposed by Cho et al. TPE was not performed in a protocol-defined manner. Patients were classified as achieving complete response (CR) if they showed disappearance of schistocytes, resolution of any changes in mental status, normalization of lactic dehydrogenase, and were not receiving red blood cells and platelet transfusions. Patients were considered to have achieved no response (NR) when they showed no improvement of laboratory features, remained dependent on red blood cell and/or platelet transfusions, or died with active TA-TMA. Subjects were considered to have a partial response (PR) when they did not meet the criteria for either CR or NR (BMT 2010; Blood 2020).ResultsTA-TMA was diagnosed at a median time of 64.5 [IQR 38.8-158] days post-HSCT. The 42 men (51.2%) and 40 women (48.8%) had an average age of 35.3 years. Renal involvement (59.8%), central nervous system dysfunction (70.7%), gastrointestinal (GI) bleeding (73.2%), and concomitant acute graft-versus-host disease (aGVHD, 78%) were common in our cohort of TA-TMA patients.All 82 patients in our analysis received TPE, and adjunctive TA-TMA-targeted therapy included the use of rituximab (11 patients), rituximab plus eculizumab (1 patient), and defibrotide (1 patient). However, the additional therapy showed no significant difference between the response and nonresponse groups. The median time from TA-TMA to TPE initiation was 8 days [IQR 2.0-16.5], and the cumulative volume of TPE was 6 L [IQR 3.6-8.5]. Our data revealed that the overall response was 52.4% (43/82), comprising 4 CRs and 39 PRs. Early TPE initiation trended towards a better response, but this difference was not statistically significant. The multivariate analysis showed that patients with GI bleeding (OR, 6.26; 95% CI, 1.30-30.12), grade III-IV aGVHD (OR, 5.00; 95% CI, 1.50-16.68), lower cumulative volume of TPE (OR, 8.51; 95% CI, 1.91-38.05), and severe anemia (OR, 7.48; 95% CI, 2.20-25.49) were less likely to respond to TPE.Regarding treatment outcome, 57% (47/82) of cases survived 100 days post HSCT, and 20% (16/82) survived 100 days after the diagnosis of TA-TMA. With a median follow-up of 467 days [IQR 248-1002], the OS at 1 year after TA-TMA was 15%. The leading causes of death were infection, active TA-TMA, and multiple organ dysfunction syndrome (MODS). The Kaplan-Meier analysis showed that GI bleeding, grade III-IV aGVHD, and no response to TPE were associated with poor survival at 1-year post TA-TMA (Figure 1). By multivariate analysis, TA-TMA patients treated with TPE had dismal survival with GI bleeding, lower loading volume of TPE, and elevated total bilirubin.ConclusionsThe results of this large cohort of real-world practice indicate that TPE may be effective for TA-TMA depending on given clinical circumstances. Our data underscore that GI bleeding is independently associated with poor response to TPE and mortality, while grade III-IV aGVHD is again confirmed as predicting a dismal response to TPE. We hypothesize that higher volume of TPE is warranted to achieve resolution and favorable outcome of TA-TMA. Multicenter prospective studies are required to further verify whether these patients could benefit from TPE and seek a paradigm for TPE in the management of TA-TMA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series

Background: Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. Methods: Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35–50 mL/kg.h replacement fluid at the rate of 3–5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1–1.5-fold of one body calculated plasma volume in each section. Results: All 3 fatal TEN (with >30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3–5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant Acinetobacter baumannii. Conclusion: After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

Clinical experience with maintenance therapeutic plasma exchange in refractory generalized myasthenia gravis.

Despite the availability of several immunomodulatory therapies, about 20% of myasthenia gravis (MG) patients remain refractory to conventional treatments. There is limited evidence to support the use of maintenance therapeutic plasma exchange (TPE) therapy for refractory generalized MG. Retrospective chart review of 14 patients with refractory generalized MG treated for 12 months with maintenance TPE therapy. Outcome measures were myasthenia gravis composite (MGC) score, myasthenia gravis activities of daily living (MG-ADL), number of acute exacerbations, medication changes, and adverse events. Data were collected at 3 monthly intervals for 12 months before and after initiation of TPE therapy. Clinically meaningful reductions in mean MG-ADL (>2 points) (mean MG-ADL score: 9.9 ± 0.5; 12-month pre-TPE to 5.2 ± 0.9; 12-month post-TPE) and MGC (>3 points) (mean MGC score: 25.2 ± 1.6; 12-month pre-TPE to 11.7 ± 1.4; 12-month post-TPE) were observed at 3months following initiation of TPE and were maintained up to 12 months in all patients. After 12 months of TPE therapy, all patients had a significant reduction in daily prednisone and pyridostigmine use. Patients previously on IVIG or rituximab therapy were successfully weaned off both treatments. There was a significant reduction in acute MG exacerbations; 7.8 ± 1.1 mean exacerbations/patient (12-month pre-TPE) to 2 ± 1.1 mean exacerbations/patient (12-month post-TPE). Over a period of 12 months, maintenance TPE therapy improved MG-ADL, and MGC with decreased immunosuppressant requirement, while being well-tolerated.

Projected Cost Savings of a Plasmic Score-Based Approach to Patients with Suspected Thrombotic Thrombocytopenic Purpura

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but deadly thrombotic microangiopathy (TMA) that is caused by a severe acquired deficiency in the ADAMTS13 enzyme. The PLASMIC clinical scoring system categorizes patients with suspected TTP as being at low (score <5), intermediate (score = 5), or high (score >5) risk of severe ADAMTS13 deficiency. Here we have modeled the potential cost savings of a management approach that incorporates the PLASMIC score to defer testing and treatment for low risk patients and compared this approach to one in which ADAMTS13 testing requests require pre-approval by the blood transfusion service.Methods: We utilized an expanded dataset from the Harvard TMA Research Collaborative, a multi-institutional registry consisting of all consecutive patients with TMA and suspected TTP seen at three large academic medical centers between 2004-2015 (n=372). We leveraged existing differences in practice patterns between participating institutions to identify hospitals that do not regulate ADAMTS13 testing (Group A, N=278) and those that employed a restrictive strategy in which requests for ADAMTS13 testing were subject to approval by the blood transfusion service (Group B, N=94). A decision tree-based cost analysis algorithm was utilized to assess the potential cost savings from utilizing the PLASMIC score to defer ADAMTS13 testing in low-risk patients in Group A. We also compared total TTP-related costs (diagnosis and treatment) between Group A (both the unregulated and PLASMIC-based approach) and Group B.Results: Different practice patterns between Groups A and B provided a “natural experiment” to study the cost implications of different management approaches for TTP. In Group A, we noted a 435% increase in ADAMTS13 assays sent between 2004-2015 (test for trend p<0.0001), driven largely by patients without signs of TMA and/or with low-risk PLASMIC scores. This growth in testing was absent in Group B (test for trend p=0.98). The number of TTP cases per 100,000 admissions did not differ the two groups (p=0.19) and remained unchanged over time (p=0.67 and p=0.31 for Groups A and B, respectively). To assess the cost differences between management approaches, we generated a decision tree containing nodes with important clinical choices such as ADAMTS13 testing, expert consultation, and initiation of therapeutic plasma exchange (TPE). The tree excluded patients without thrombocytopenia or schistocytes at its first branch point. In projecting the number of ADAMTS13 tests through 2025, we found that Group A's TTP-related costs were significantly higher and would result in over $11 million in increased costs between 2004-2025 compared to Group B (Figure 1). Under a PLASMIC score-based approach, patients at Group A institutions with a low risk score would not receive upfront ADAMTS13 testing or downstream care for TTP and instead be closely observed while being worked up for alternative causes of TMA. Considering 2015, the latest year for which complete data are available, applying a PLASMIC-score based approach to the Group A institutions was projected to reduce TTP-related costs from $610,471 to $473,058 (23%) per 100,000 admissions (Table 1). By comparison, in 2015 Group B TTP-related costs were $152,000 per 100,000 admissions. Assuming current trends, a PLASMIC score-based strategy within Group A would result in over $3.2 million (23%) saved between 2004-2025 compared to the current unregulated approach, primarily due to decreased rates of testing, expert consultation, and TPE.Conclusions: Our data suggest that institutions with an unregulated approach to ADAMTS13 testing could potentially realize cost savings by implementing a strategy based on risk stratification of suspected TTP cases by PLASMIC score. In terms of normalized costs, a PLASMIC-score based strategy would be intermediate between an unregulated testing approach and one that employs live oversight of ADAMTS13 testing by the blood transfusion service. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Benchmarking the centralized urgent plasma exchange service for patients admitted with a diagnosis of suspected acquired thrombotic thrombocytopenic purpura at a large healthcare system.

Consensus guidelines recommend that therapeutic plasma exchange (TPE) should be started within 4 to 8hours after the diagnosis of suspected acquired thrombotic thrombocytopenic purpura (aTTP). This study aimed to audit the steps from diagnosis to initiation of plasma exchange at a centralized apheresis service. A retrospective review of the electronic medical record and laboratory information systems from January 1, 2014 to August 31, 2017 was conducted to identify all patients with suspected aTTP undergoing TPE. Demographics, comorbidities, pertinent laboratory tests, and temporal TPE procedural data were collected. The median (5th-95th percentile) time from request to initiation of TPE was 5.4 (3.2-10.6) hours. TPE was initiated within 8hours in 94 of the 108 patients (87.0%). The median (5th-95th percentile) time from request to central venous access was 2.5 (0.5-6.9) hours and from request to plasma product issuance from the blood bank was 3.4 (1.6-8.1) hours. aTTP patients in whom TPE was initiated greater than 6hours from request did not have worse outcomes compared to those with TPE initiation within 6hours: in-hospital mortality (2/14 [14.3%] vs 2/21 [9.5%], P= 0.66), median length of stay (9.0 [4.7-44.1] vs 8.3 [3.9-27.0] days, P= 0.76), and median number of days to durable platelet count recovery (4.5 [2.0-9.0] vs 4.0 [2.0-18.0] days, P= 0.66). The 4 to 8-hour target window from TPE request to initiation appears feasible for a centralized apheresis program servicing a large healthcare system.

Variable response to therapeutic plasma exchange in pediatric anti-NMDA receptor encephalitis.

Anti-NMDA receptor encephalitis in an acute form generally presents with abnormal movements and psychiatric symptoms. Therapeutic plasma exchange has been considered to be one of the first line treatment options. This report highlights the role of plasma exchange in anti-NMDA receptor encephalitis in pediatric patients. This is a retrospective analysis of four cases of a severe form of encephalitis due to anti-NMDA receptor antibody. All these four patients were evaluated for clinical and laboratory profile before plasma exchange. Plasma exchange was performed with Cobe Spectra Version 7.0(Terumo BCT, USA), and 5% albumin and fresh frozen plasma were used as replacement fluid. A total of 20 procedures (range: 2-8/patient) were performed on four patients on an alternate day basis. Slow recovery and long-term hospitalization (range: 25-70 days) was observed in all these patients and may be due to delayed initiation of plasma exchange. One patient was lost in follow up while another one had fatal consequences after one month of discharge from the hospital. Early diagnosis and timely initiation of therapeutic plasma exchange along with immunosuppressive therapy hasten the recovery, duration of hospitalization and yield a better outcome.

Therapeutic plasma exchange: A potential management strategy for critically ill MIS-C patients in the pediatric intensive care unit

This study aimed to evaluate the effectiveness and the role of therapeutic plasma exchange (TPE) in treatment of children with severe MIS-C. In addition, we assessed demographic data, clinical features, laboratory abnormalities, underlying conditions, treatments, and outcomes. Patients with severe MIS-C who were admitted to the pediatric intensive care unit (PICU) between September 01 and October 05, 2020 were included in this observational, descriptive, retrospective study. The data collected included the patients’ demographic data, presenting symptoms, clinical features, laboratory parameters, diagnostic investigations, and medications. Of 27 children with MIS-C, 63 % were male. The median age of the patients was nine years. Intravenous immunoglobulin and corticosteroids were used for treatment in 100 % of the patients, anakinra in 51.8 %, vasopressors in 85.1 %, noninvasive mechanical ventilation in 25.9 %, and invasive mechanical ventilation in 18.5 %. Ten of the 27 patients (37 %) underwent TPE. In the patients who underwent TPE, the median PELOD score was 21 (IQR: 11–30.25) before TPE and 10 (IQR: 10–11) after TPE (p < 0.001). Moreover, their median left ventricular ejection fraction (LVEF) was 52 % (IQR: 49.25 %–55 %) before TPE and median LVEF was 66.5 (IQR: 58 %–68.5 %) after TPE (p = 0.012). The median number of TPE sessions was three (IQR: 2–4.75). The mortality rate of the patients with severe MIS-C admitted to the PICU was 7.4 %. We suggest that TPE should be considered as a therapeutic option in children with severe MIS-C. Early initiation of TPE followed by immunomodulatory therapy in critically ill children with MIS-C may help improve clinical and laboratory outcomes.

Understanding the role of therapeutic plasma exchange in COVID-19: preliminary guidance and practices.

Background and objectivesCytokine release syndrome in COVID‐19 is due to a pathological inflammatory response of raised cytokines. Removal of these cytokines by therapeutic plasma exchange (TPE) prior to end‐organ damage may improve clinical outcomes. This manuscript is intended to serve as a preliminary guidance document for application of TPE in patients with severe COVID‐19.Material and methodsThe available literature pertaining to the role of TPE for treatment of COVID‐19 patients was reviewed to guide optimal management. It included indication, contraindication, optimal timing of initiation and termination of TPE, vascular access and anticoagulants, numbers and mode of procedures, outcome measures and adverse events.ResultsOut of a total of 78 articles, only 65 were directly related to the topic. From these 65, only 32 were acceptable as primary source, while 33 were used as supporting references. TPE in critically ill COVID‐19 patients may be classified under ASFA category III grade 2B. The early initiation of TPE for 1–1·5 patient’s plasma volume with fresh frozen plasma, or 4–5% albumin or COVID‐19 convalescent plasma as replacement fluids before multiorgan failure, has better chances of recovery. The number of procedures can vary from three to nine depending on patient response.ConclusionTPE in COVID‐19 patients may help by removing toxic cytokines, viral particles and/or by correcting coagulopathy or restoring endothelial membrane. Severity score (SOFA & APACHE II) and cytokine levels (IL‐6, C‐reactive protein) can be used to execute TPE therapy and to monitor response in COVID‐19 patients.

Immature platelet dynamics correlate with ADAMTS13 deficiency and predict therapy response in immune-mediated thrombotic thrombocytopenic purpura

IntroductionThrombotic thrombocytopenic purpura (TTP) requires prompt initiation of therapeutic plasma exchange (TPE) to avoid significant morbidity and mortality. ADAMTS13 activity testing defines TTP, however, at most institutions this is a send-out test and therapy is often initiated prior to measurement availability. We describe our experience looking at absolute immature platelet counts (A-IPC) in patients suspected with TTP at presentation and in response to therapy. Materials and methodsForty-eight patients treated for suspected TTP with A-IPC measure on admission and during hospitalization met inclusion criteria. Of these patients, sixteen had new-onset TTP (ADAMTS13 < 10%), ten were relapsing patients (first diagnosis prior to study period), and 22 were classified as non-TTP (ADAMTS13 ≥ 10%). ResultsPatients with ADAMTS13 deficiency (TTP) had A-IPC different from those without deficiency. A-IPC of 1–2 × 109/L at presentation had high sensitivity and specificity with a negative predictive value of 95.5 to 100%. Two-to-three-fold increases in A-IPC from count prior to TPE initiation was limited to ADAMTS13 deficient patients who was the group responding to therapy. Increases were higher in patients with new disease onset compared to relapsing patients (p = 0.018). Likewise, relapsing patients' A-IPC appeared dependent upon platelet count at time of relapse. A-IPC predicted and correlated with ADAMTS13 deficiency in new-onset TTP (p = 0.0002). ConclusionsOnly patients with A-IPC-fold increases responded to TPE with platelet count normalization. Our results represent a proof of concept that A-IPC measurements can supplement ADAMTS13 testing and determine response to TPE. Future studies are needed to establish ways to apply these findings in the setting of suspected TTP.

Efficacy of 4-hour rescue therapeutic plasma exchange in severe septic shock patients.

Early intervention for septic shock is crucial to reduce mortality and improve outcome. There is still a great debate over the exact time of therapeutic plasma exchange (TPE) administration in septic shock patients. This study aims to investigate the effect of early initiation (within 4 hours) of TPE in severe septic shock on hemodynamics & outcome. We conducted a prospective, before-after case series study on 16 septic shock patients requiring high doses of vasopressors admitted in two ICUs from Cairo, Egypt. All of our patients received TPE within 4 hours of ICU admission. The fresh frozen plasma exchange volume = 1.5 × plasma volume. In the 16 patients included in the study, mean arterial pressure was significantly improved after the initial TPE (p < 0.002) and norepinephrine dose which significantly reduced post TPE (p < 0.001). In addition, norepinephrine dose to mean arterial pressure significantly improved (p < 0.001). There was reduction of a net 6 hours fluid balances following the first TPE were observed in all the patients (p < 0.03) by a mean of 757 ml. Systemic vascular resistance index was markedly improved post-TPE along with statistically improved cardiac index (p < 0.01). Stroke volume variance was also significantly decreased after the TPE sessions (p < 0.01). C-reactive protein significantly improved after TPE (P < 0.01). Early initiation of TPE in severe septic shock patients might improve hemodynamic measures.