To Therapeutic Plasma Exchange Research Articles

Experience of a therapeutic plasma exchange program in a pediatric intensive care unit: A single-center retrospective observational study from Canada

Background: Pediatric intensive care units (PICUs) may not have timely access to therapeutic plasma exchange (TPE) for critically ill patients. The purpose of this study was to evaluate the common indications for TPE in a smaller tertiary PICU-developed TPE program and to evaluate the associated predictors of mortality. We hypothesized that a PICU-developed TPE program could provide timely access for a wide breadth of pathologies and can be delivered safely. Subjects and Methods: This was a retrospective case-comparison within-cohort study in a PICU from Canada. Data from pediatric patients between October 2015 and January 2022 was examined. The study included all patients < 18 years admitted to the PICU and requiring TPE. Multiorgan dysfunction syndrome (MODS) was defined to agree with the International Pediatric Sepsis Consensus Conference. Proportions, medians, and interquartile ranges (IQR) were calculated where appropriate. Results: Twenty-five patients with a median age of 14 years underwent 118 acute TPE runs. The most common diagnosis (24%) was MODS. The median time from PICU admission to initiation of TPE was 38 h (IQR: 5–113.5) hours. The median PICU length of stay was 10 (IQR: 5.5–26) days. Twenty percent (n = 5) of patients who received TPE acutely in the PICU required chronic TPE. There were no adverse events. Conclusions: TPE may be delivered quickly and safely from a small PICU for many indications, with MODS being the most common.

P‐TA‐3 | Characterization of Spirometric Response to Therapeutic Plasma Exchange (TPE) and Factors Associated with Respiratory Distress in Myasthenia Gravis Patients

P‐TA‐3 | Characterization of Spirometric Response to Therapeutic Plasma Exchange (TPE) and Factors Associated with Respiratory Distress in Myasthenia Gravis Patients

In patients with suspected immune TTP, admission source impacts hospital length of stay and time to therapeutic plasma exchange impacts clinical outcomes

IntroductionWhen immune thrombotic thrombocytopenic purpura (TTP) is suspected, outcomes are impacted by time to therapeutic plasma exchange (TPE). We evaluated the impact of time to TPE on outcomes in suspected TTP cases admitted through the Emergency Department (ED) vs. transferred from another facility (Transfer). Materials and methodsIn a retrospective analysis of the National Inpatient Sample, we examined the association between TTP outcomes and admission source (ED vs. Transfer) for the primary outcome of time to TPE. A second stratified analyses within each analytic group examined the association of time to TPE (<1 day, 1 day, 2 days, and >2 days) and outcomes for the composite outcome of mortality, major bleeding and thrombosis. ResultsOf 1195 cases, 793 (66 %) were admitted through the ED and 402 (34 %) were transferred. Compared to ED cases, Transfers had a longer hospital length of stay (14.69 vs. 16.65 days, p = 0.0060). For ED cases, TPE after >2 days was associated with higher odds of the composite outcome (OR = 1.68 95 % CI: 1.11–2.54; p = 0.0150) and mortality (OR = 3.01 95 % CI: 1.38–6.57; p = 0.0056). For Transfers, TPE on day 2 was associated with higher odds of the composite outcome (OR = 3.00 95 % CI: 1.31–6.89; p = 0.0096) and mortality (OR = 4.95 95 % CI: 1.12–21.88; p = 0.0350). ConclusionsIn suspected TTP admitted through the ED or transferred, there was no significant difference in time to TPE. A longer time to TPE was associated with worse outcomes. Future studies should evaluate strategies to decrease initial time to TPE.

Outcomes of ABO Incompatible Kidney Transplantation:A Single Center Experience

Background: Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease (ESRD). General organ donor shortage remains an important limitation on KT, given the increasing number of patients waiting for transplantation. This has led to the adoption of different strategies to increase the pool of donors, such as ABO incompatible (ABOi) living KT. In this single center study, we retrospectively evaluated all donor/recipient pairs proposed for ABOi KT since the beginning of this transplantation program in our hospital in 2014. Methods: Between November 2014 and March 2022, 609 deceased donor and 223 living donor KT were performed in our center. Seventy-one donor/recipient pairs were proposed for ABOi KT and were evaluated for ABO/Rh group, Coombs tests, human leukocyte antigen (HLA) type I (A, B, C) and II (DR) high resolution genotyping and receptor to donor isoagglutinin titers and HLA antibodies. Recipients with immunoglobulins G (IgG) and/or M (IgM) isoagglutinin titers &gt; 1:512 and/or with HLA donor specific alloantibodies (DSAs) were excluded from the ABOi transplantation program. Isoagglutinins removal was performed recurring to therapeutic plasma exchange (TPE) and/or immunoadsorption techniques. Transplanted patients were evaluated for demographic data, diagnosis, relationship with donor, sessions of antibodies removal, pre- and post-KT isoagglutinin titers, graft function, transfusion support, significant complications and overall patient survival. Results: Eighteen patients (14 males and 4 females) were transplanted with an ABOi graft out of 71 ABOi studied pairs. Median baseline IgG and IgM isoagglutinin titers were 1:32 (min 1:2, max 1:256) and 1:8 (min 1:2, max 1:32), respectively. Fifteen patients (83.3%) had pre-KT TPE and/or immunoadsorption sessions for isoagglutinin removal (mean 2.4 ± 1.8 session per patient). Seven patients (36.8%) were submitted to post-KT TPE (mean 1.9 ± 3.2 session per patient). No acute antibody mediated rejection was observed and overall graft survival was 100% on a follow-up period between 3 and 92 months (47.6 ± 25.2 months). All patients were dialysis-free with serum creatinine steady levels (median 1.4 mg/dL) at 47.6 ± 25.2 months of follow up. Conclusion: These results confirm that ABOi KT is a viable treatment for patients with ESRD, thus expanding living donor pool and reducing access time to transplantation.

Therapeutic plasma exchange for the treatment of refractory necrotizing autoimmune myopathy.

IntroductionNecrotizing autoimmune myopathy (NAM) is strongly associated with pathognomonic autoantibodies targeting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) or signal recognition particle (SRP), whose levels in turn are correlated with serum creatine kinase (CK) and necrosis. Thus, NAM may be amenable to therapeutic plasma exchange (TPE) to remove pathogenic antibodies and improve patient symptoms.MethodsA retrospective case series and literature review of patients presenting with NAM and undergoing treatment with TPE was performed. Clinical data including patient demographics, symptoms, physical exam findings, muscle biopsy, lower extremity imaging, prior therapy, and duration from diagnosis to TPE initiation were collected retrospectively for adult patients with NAM treated with TPE after failing to respond to immunomodulatory therapy. Laboratory data including change in CK levels and myositis‐specific antibody titers from baseline were measured in some patients.ResultsSix patients (median age at diagnosis 52.5 years, interquartile range [IQR] 35.8‐64.5 years, four male/two female) underwent a median of 7.5 (IQR: 5‐10) TPE procedures with 5% albumin as replacement. All patients exhibited a statistically significant reduction in CK level from pre‐TPE baseline (range: 43.0%‐58.7% reduction). Responses in this cohort were best in patients with antibodies targeting HMGCR and SRP, which are most strongly associated with NAM. These results compare favorably to a literature review of NAM patients (n = 19) treated with TPE, who also exhibited positive clinical and laboratory responses across varying treatment lengths.ConclusionTPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression.

Therapeutic apheresis and non‐blood donor related apheresis current practices at various blood centres of healthcare organisations of India: A brief online survey

AbstractObjectivesTo determine the variability in therapeutic apheresis (TA) and non‐blood donor related apheresis practices, and the extent of expertise and knowledge of blood centre staff.BackgroundApheresis activity that was earlier limited to therapeutic plasma exchange (TPE) and donor apheresis at few centres in India has seen remarkable surge involving many centres practising TA and non‐blood donor related apheresis. The decentralised transfusion medicine practice in country has resulted in wide variability of knowledge and practice of TA. An online survey was conducted to achieve study objectives.Study design and methodsA 22 questionnaire survey was sent to the 215 blood centres through e‐mail link focussing on three aspects; basic information of the participating centres, details of TA procedures and education and training levels of the staff.ResultsMajority (71.9%) of centres were teaching institutions among analysed 57 centres. TPE (85.9%) and therapeutic cytapheresis (71.9%) were the most common TA procedures. The clinical haematology (68.4%) followed by neurology (64.9%) were the specialities utilising TA. The 64.9% centres used continuous flow cell separator and central venous access (52%) was preferred vascular access. A combination of normal saline, fresh frozen plasma and 5% albumin replacement fluid was first choice. Doctors involved in TA were trained in apheresis during their MD/DNB degree, but no structured training program existed for other category of staff.ConclusionThere was a wide variability in TA practice in India and a dedicated training program for all categories of staff was emphasised by majority of participants.

INTEGRATED EFFICACY RESULTS FROM THE PHASE 2 AND PHASE 3 STUDIES WITH CAPLACIZUMAB IN PATIENTS WITH ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA

An integrated analysis based on the Phase 2 TITAN (NCT01151423) and Phase 3 HERCULES (NCT02553317) studies with caplacizumab (CPLZ) in acquired thrombotic thrombocytopenic purpura (aTTP) was performed to assess treatment differences on efficacy and safety outcomes that may have been undetected in the individual trials. In both trials, patients with an acute episode of aTTP were randomized to receive CPLZ or placebo (PBO) in addition to therapeutic plasma exchange (TPE) and immunosuppression. All randomized patients from both studies were included in the integrated efficacy analyses (CPLZ: n=108; PBO: n=112), and those who received at least 1 dose of the study drug were included in the safety analyses (CPLZ: n=106; PBO: n=110). CPLZ significantly reduced mortality (0 vs 4 deaths; P&lt;0.05) and refractory TTP (0 vs 8 events; P&lt;0.05) versus PBO and improved time to platelet count response (hazard ratio, 1.65; P&lt;0.001). CPLZ also reduced the composite endpoint of TTP-related death, exacerbation, or any treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P&lt;0.001) and median number of TPE days (5.0 vs 7.5 days) versus PBO. Mild mucocutaneous bleeding was the main safety finding for CPLZ. This integrated analysis provided new evidence that CPLZ prevents mortality and refractory disease in aTTP and reinforced the individual trial efficacy and safety findings. No new safety signals were identified for

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P=0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 =0.9182) and patient survival (P=0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P=0.0074) and patient survival (P=0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

Atypical hemolytic uremic syndrome precipitated by thyrotoxicosis: a case report

BackgroundAutoimmune thyroid disease (AITD) has a complex pathogenesis and is associated with the development of autoimmunity against the thyroid. Graves’ disease and Hashimoto’s thyroiditis are the two main types of AITD, and they are characterized by thyrotoxicosis and hypothyroidism, respectively. Atypical hemolytic uremic syndrome (aHUS) is a rare disease, presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. aHUS is caused by dysregulation of the alternative complement pathway, and its co-existence with AITD is rare.Case presentationWe report the case of a 12-year-old girl with recent onset thyrotoxicosis. She was first treated with propylthiouracil for 2 months and then developed AITD presenting as abrupt-onset thrombocytopenia, acute kidney injury, and microangiopathic hemolytic anemia. Thyroid function tests favored hyperthyroidism, with increased free T4 and free T3 levels and a very low level of thyroid-stimulating hormone (TSH). We suspected aHUS, and the patient’s condition responded dramatically to therapeutic plasma exchange (TPE) with disease remission. She experienced recurrent aHUS after subsequently receiving methimazole for 1 month, and in the recurrent episode, her condition responded again to TPE and concomitant glucocorticoids. She achieved euthyroidism with thiamazole ointment treatment, without aHUS recurrence during the 6-month follow-up. Mycophenolate mofetil was administered to manage proteinuria after 3 months of treatment with the steroid and angiotensin-converting enzyme inhibitor.ConclusionsThe coexistence of aHUS and AITD in this case is likely more than coincidence, because both are autoimmune in origin. aHUS is associated with a high mortality without appropriate therapy, and treatment with TPE and adjunct immunosuppressants can be helpful.

Therapeutic plasma exchange for neuromyelitis optica spectrum disorder: A multicenter retrospective study by the ASFA neurologic diseases subcommittee.

Neuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized. Our study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE. This is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease. The primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment. We evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non-Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted "mild" to "moderate" clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment. TPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well-tolerated and had a low severe adverse event profile.

ACTH Gel in Resistant Focal Segmental Glomerulosclerosis After Kidney Transplantation.

Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange (TPE) and/or rituximab. We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large US transplant centers between April 2012 and December 2016. Proteinuria was measured by urine protein to creatinine ratio. We identified 20 cases of posttransplant recurrent and de novo FSGS resistant to conventional therapy with TPE and rituximab. Mean ± SD age was 49 ± 15.5 years, 14 (70%) were male, 13 (65%) were whites, and 8 (38%) had previous kidney transplants. Median (interquartile range) of recurrent and de novo FSGS was 3 (0.75-7.5) months posttransplant. The majority of patients, 15 (75%), received TPE as a treatment at the time of diagnosis and 10 (50%) received rituximab, which was started before the use of ACTH gel. There was a significant improvement of urine protein to creatinine ratio from a mean ± SD of 8.6 ± 7.6 g/g before ACTH gel to 3.3 ± 2.3 g/g after the use of ACTH gel (P = 0.004). Ten (50%) patients achieved complete or partial remission. Although, the response varied among the recipients, ACTH gel might be an effective therapy for posttransplant resistant FSGS cases that fail to respond to TPE and rituximab.

A Phase II Study Evaluating the Efficacy of Rituximab in the Management of Patients with Relapsed or Refractory TTP

Background: As many as 30-50% of patients diagnosed with Thrombotic Thrombocytopenic Purpura (TTP) either relapse or become refractory to therapeutic plasma exchange (TPE). There remains a pressing need to evaluate novel treatments for these patients. Rituximab is a chimeric anti-CD20 monoclonal antibody that has demonstrated efficacy potentially by eliminating active B-lymphocytes and production of ADAMTS 13 inhibitor considered central to the pathogenesis of TTP.Intervention: We conducted a prospective multi-center phase II open-label trial in Canadian hospital-based apheresis units to evaluate the efficacy of rituximab in the management of adult patients with relapsed or refractory TTP. Functional and antigenic ADAMTS13 enzyme, inhibitor levels and anti-CD 20 were measured at initiation, 8, 12, 24 and 52-weeks as well as routine hematologic parameters, complete remission, rate of relapse, overall mortality and adverse events. Rituximab was administered intravenously once weekly for a total of 4 doses at 375 mg/m2 in eligible consenting patients.Results: Twenty refractory and 20 relapsing TTP patients were enrolled (N=40). A complete response (CR) was defined by a platelet count >150 x 109/L, an LDH <1.5 times the upper limit of normal, absence of progressive neurologic symptoms and no further need for TPE. At week 8, 77% of refractory patients and 90% of relapsed patients were in CR. At week 52, 15/20 refractory patients (3 deaths, 1 lost to follow-up) and 18/20 of relapsed patients (1 withdrew, 1 lost to follow-up) were alive and in CR. Of the 40 patients enrolled a total of 3 patients died; all in the refractory arm: two with functional ADAMTS13 <10% and detectable inhibitor. Two deaths were related to fungal infection (week 2) and active TTP (week 8). A third death was attributed to thrombotic complications at week 29. All refractory patients with normal ADAMTS13 enzyme at baseline had a complete response at week 8 and remained in remission for the remainder of follow-up (52 weeks). Despite being in complete hematological and clinical remission, relapsing TTP patients still had a positive inhibitor at 24 (50% of patients) and 52 weeks (10% of patients). All patients had < 3% CD 20+ B-lymphocytes at 8 and 12 weeks post rituximab. Median platelet counts in the refractory group recovered more slowly than in the relapsing TTP patients. By week 8 refractory TTP patients received a median of 26 plasma exchanges and relapsed patients received a median of 11(P<0.001).Conclusion: At the conclusion of this study the overall mortality rate was 8%, 15% (95% CI: 5% to 36%) for the refractory group and 0% (95% CI: 0% to 16%) for the relapsed group. Nine refractory patients were dialysis-dependent at baseline and only 2 had a serum creatinine >250 µmol/L and remained on dialysis at week 52. These patients had normal ADAMTS13 enzyme measurements throughout the time period of the study. Results of this study indicate that TPE and rituximab is an effective combination in patients with relapsed or refractory TTP. DisclosuresFoley:Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Hoffman-LaRoche: Consultancy, Honoraria, Research Funding; Jansen: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Off Label Use: Rituxan is a CD20-directed cytolytic antibody indicated for the treatment of patients with: -Non-Hodgkin’s Lymphoma (NHL) (1.1) -Chronic Lymphocytic Leukemia (CLL) (1.2) - Rheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately-to severely-active RA who have inadequate response to one or more TNF antagonist therapies (1.3) . Arnold:GSK: Honoraria, Research Funding; Hoffman-LaRoche: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Clark:Alexion: Honoraria; CSN: Honoraria; ASN: Honoraria; Octapharm: Honoraria; Danone Research: Honoraria.

The Clinical Response to Therapeutic Plasma Exchange (TPE) in Patients With Suspected Lung Transplant Rejection Associated With De Novo Class II HLA Donor-Specific Antibodies (DSA)

The recognition and utility of diagnostic criteria for humoral antibody-mediated rejection (AMR) in solid organ transplantation besides renal transplants are not well characterized. The role of TPE in treatment of suspected humoral AMR of lung transplants is similarly indeterminate with little efficacy described for using apheresis in this setting. We present 2 cases of suspected AMR in lung transplant recipients …

Relapses of thrombotic thrombocytopenic purpura after treatment with rituximab

Rituximab has been added to therapeutic plasma exchange (TPE) in the last 10 years for refractory thrombotic thrombocytopenic purpura (TTP). We performed a retrospective single institution study to determine if patients with TTP treated with TPE and rituximab experienced relapses. We reviewed the electronic and apheresis records of patients treated between 2003 and 2008 and collected the following parameters: demographics, laboratory results, treatment characteristics, and follow-up. We identified 12 patients with ADAMTS13 <5% due to an inhibitor who received TPE and rituximab during the study period. The mean number of TPEs required to achieve remission was 24 ± 3, time to remission was 28 ± 3 days, and hospital length of stay was 36 ± 4 days. During a mean follow-up of 73.4 ± 6 months, four patients (33%) relapsed. On average, relapse occurred at 62 ± 8.5 months postachievement of remission. The one-year, three-year, and five-year relapse free-survival (RFS) rates were 92%, 75%, and 75%, respectively. On multivariate analysis, we failed to identify independent predictors of relapse. This retrospective analysis does not support the notion that rituximab prevents or decreases the rate of relapse in TTP. Prospective randomized studies are needed to confirm this observation.

Rituximab Does Not Prevent Relapse in Patients with Thrombotic Thrombocytopenic Purpura

AbstractAbstract 3318 Objective:In the last decade, rituximab has been added to therapeutic plasma exchange (TPE) to treat patients with thrombotic thrombocytopenic purpura (TTP) who appear resistant to TPE. We sought to determine first if rituximab prevented TTP relapse. In addition, if relapse has occurred, we compared the rates of relapse of patients treated with TPE alone with those treated with a combination of TPE and rituximab. Methods:We retrospectively reviewed the medical records of all adult patients treated for TTP between 2003 and 2008 at our institution. TTP was defined as thrombocytopenia, hemolytic anemia and ADAMTS13 activity less than 10% due to an inhibitor. None of the patients had congenital TTP. Patient demographics, laboratory data, treatment characteristics and follow up details were collected from their electronic and apheresis' medical records. Kaplan-Meier curves were drawn for survival and Cox proportional hazards models were applied to look for independent predictors of relapse-free survival (RFS). Results:A total of 20 patients underwent TPE only (Group 1) as compared to 18 patients who also received rituximab during admission with TTP (Group 2). Table 1 shows that both groups were balanced at baseline for demographic and laboratory data. However, patients in group 2 had longer duration of hospital stay (p<0.0001), underwent more TPE procedures (p<0.0001) and took longer to achieve remission (p<0.0001). The mean follow up in group 1 was 77.5 (±22.4) months and in group 2 was 68.6 (±28.5) months. At follow-up, 5 patients from group 1 relapsed (25%) as compared with 6 patients from group 2 (35%) (p=0.50). The 1-year, 3-year and 5-year RFS rates were 95%, 85% and 74% for group 1, and 94%, 76% and 71%, respectively, for group 2 (p=0.53 using log rank test). On univariate analysis, only age at the time of treatment (p=0.05) and duration of follow-up after treatment (p=0.03) were predictors of relapse. However, on multivariate analysis, no independent predictors of relapse were identified. Conclusion:Rituximab does not prevent or reduce rates of relapse when used with TPE in patients with TTP. Since rituximab was added to patients later in their TPE course due to delayed response to treatment, it may yet have a role in decreasing the number of TPEs needed to achieve a response if it were started earlier during hospitalization for TTP.Table 1Baseline characteristics, treatment details and follow-up dataTPE only (n=20)TPE + Rituximab (n=18)p-valueRace0.54White3 (15%)2 (11%)African-American17 (85%)15 (83%)Asian01 (6%)Gender (M/F)7/137/110.80Age38.7 ± 13.344.1 ± 15.20.25Previous therapy0.47None15 (75%)11 (61%)Corticosteroids1 (5%)0Cytotoxics1 (5%)1 (6%)Both3 (15%)6 (33%)Creatinine (mg/dL)1.65 ± 1.051.45 ± 0.480.46Lactate dehydrogenase (U/L)1520 ± 7921309 ± 6160.37Hemoglobin (g/dL)9.1 ± 1.88.4 ± 1.90.27Platelet count (×109/L)14.5 ± 6.515.2 ± 8.30.78Fever3 (15%)4 (23%)0.51Neurological symptoms14 (70%)9 (60%)0.54ADAMTS13 Inhibitor (units)3.1 ± 2.62.5 ± 2.90.52Length of stay (days)16.7 ± 10.837.6 ± 11.3<0.0001No of TPEs11 ± 625 ± 9<0.0001Median no of rituximab dosesNot applicable3.5 (1–6)Immunosuppressive therapy0.01None4 (21%)1 (6%)Corticosteroids11 (58%)4 (22%)Cytotoxics03 (17%)Both4 (21%)10 (56%)Blood stream infection3 (15%)7 (41%)0.07Time to response (days)10.2 ± 8.328.5 ± 11<0.0001Platelet count at 3 months (×109/L)236 ± 32295.13 ± 680.08Follow up (months)77.5 ± 22.468.6 ± 28.50.29Relapse5 (25%)6 (35%)0.50 Disclosures:No relevant conflicts of interest to declare.

ADAMTS13 Helps Distinguish Thrombotic Thrombocytopenic Purpura From Other Microangiopathies and Guide Necessity of Plasma Exchange Therapy

Abstract 2328 Introduction:Congenital thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13, a metalloproteinase that cleaves ultra-large VWF multimers to generate normal sized multimers present in circulation. However, acquired deficiency of ADAMTS13 due to auto-antibodies is not universally accepted as diagnostic of idiopathic TTP. Distinguishing idiopathic TTP from other thrombotic microangiopatheis (TMA) is important in guiding treatment as plasma exchange (PE) is only beneficial in TTP and select cases of other microangiopathies such as atypical HUS. Since January 2006 we routinely obtain ADAMTS13 activity performed by FRET assay from The Blood Center of Wisconsin in all patients with TMA. We report the diagnostic utility of ADAMTS13 to distinguish TTP from other forms of TMAs. Methods:A retrospective analysis was performed on consecutive patients with TMA who had ADAMTS13 assayed from January 2006 to October 2010. Demographics, presenting clinical and laboratory features are given in the Table. Responses to therapeutic plasma exchange (TPE), diagnoses at discharge, and other underlying clinical conditions were also recorded. Relevant statistical analysis was performed using unpaired t-test to compare means and Fisher's exact method for contingency tables. Results:We divided our cases based on severe ADAMTS13 deficiency (<10%) as TTP and non-severe deficiency (>20%) as TMA. TMA causes included quinine induced HUS (1), gemcitabine related HUS (1), malignant hypertension/pre-eclampsia/HEELP (3), sepsis (2), MCTD (5), malignancy (3), ITP (1), HIV/opportunistic infection (5), drugs (1), and multiple (5).TTPTMAp-valueTotal patients26 (31 episodes)27Median Age3947Sex (females %)71%56%ADAMTS13 activity <10% (normal >67%)100%0%Mean ADAMTS13 activity<10%55 ± 21%ADAMTS13 Inhibitor >0.4 units81%0%Admission platelet count x109/L (mean ± SD)25 ± 2864 ± 410.0001Admission LD units/L (mean ± SD)1005 ± 6341337 ± 14300.25Admission hematocrit % (mean ± SD)26.4 ± 7.726.8 ± 4.90.82Fever26%19%0.55Neurological symptoms58%44%0.43Creatinine mg/dL (mean ± SD)1.35 ± .932.49 ± 2.140.0094Schistocytes97%81%.0913Low haptoglobin (<16 mg/dL)92%60%.0087D-dimer elevated (>3.0 mg/L)57%57%1.0PLEX performed90150%Post treatment Platelet count x109/L (mean ± SD)212 ± 79122 ± 1260.0024Post treatment LD units/L (mean ± SD)266±91701±11010.042Mortality1-27%4%1.0[1]3 patients did not receive PLEX in TTP: 1 patient died during first PLEX, another patient (Jehovah's witness) refused FFP, and the third patient was started on steroids instead of PLEX[2]Mortality: TTP: 1-sepsis, 1-bronchiolitis obliterans, 2-did not receive standard PLEX (see notes in [1]), TMA: 1-respiratory failure Conclusions:In our experience severe ADAMTS13 deficiency appears to distinguish TTP from TMA. TMA had better mortality despite either not initiating or discontinuing PE based on ADAMTS13 levels. However, if we had continued PE in TMA then these patients would have been considered as NON-ADAMTS13 deficient TTP who responded well to PE. Disclosures:No relevant conflicts of interest to declare.

Predictors of response and relapse in a cohort of adults with thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome: a single‐institution experience

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a diagnosis of exclusion when a patient presents with the sine qua non findings of thrombocytopenia and microangiopathic hemolytic anemia without an identifiable cause. Although most patients respond to therapeutic plasma exchange (TPE), a significant number of patients relapse. The aim was to determine if clinical, laboratory, and/or treatment features could predict response and/or relapse. This study was a retrospective review of adults with TTP-HUS treated with TPE at our institution from January 1996 to February 2004. The study population consisted of 90 patients (69% female) with mean age of 45 years and mostly obese (65%). The majority of cases were considered idiopathic. Ten patients died (11%) from the disease before achieving a response, whereas 79 percent were considered responders. Obesity and severe anemia at presentation were predictors of response to TPE (p = 0.0126 and p = 0.0071, respectively). Among the responders, 28 percent relapsed in a median of 14 months. Male sex, severe thrombocytopenia (mean +/- SD, 13 x 10(9) +/- 8 x 10(9)/L), and higher lactate dehydrogenase pre-/posttreatment ratio were associated with relapse (p values of 0.0141, 0.0199, and 0.0407, respectively). ADAMTS-13 values were not obtained on enough number of patients to provide important data. Although patient and laboratory characteristics associated with response and relapse were identified, there was significant overlap between patient groups. Thus, our findings offer preliminary evidence and do not yet justify short- or long-term changes in the management of patients with TTP-HUS.

Relapse of Thrombotic Thrombocytopenic Purpura: Is It a Continuum of Disease?

The recurrence of thrombotic thrombocytopenic purpura (TTP) in 20 to 50% of patients who survive their initial episode, is not only a challenge to manage clinically, but brings to light our lack of understanding of the underlying pathophysiology. Recurrence may occur close to apparent hematologic remission or remotely, months later. Given that surveillance of TTP relies on surrogate measures such as hematologic recovery, normalization of serum lactate dehydrogenase (LDH) and resolution of clinical signs, it is plausible that some recurrences are actually a continuum of disease. Standardizing definitions for remission, exacerbation, and relapse are important for consistency of patient management and interpreting the medical literature. When TTP recurs, several adjuncts to therapeutic plasma exchange (TPE) have been used, including splenectomy, vincristine, and rituximab. Although it would seem intuitive that more severe disease would predict a greater likelihood of relapse, the degree of thrombocytopenia at presentation, the persistence of schistocytosis at discontinuation of TPE, the elevation of LDH, and the length of time to attain clinical remission are not reliable indicators of the clinical outcome of any individual TTP patient. Measurement of ADAMTS13 activity and its inhibitor offer new promise for prognostic and pathophysiologic significance; however, more extensive scientific investigation is needed.

Plasmapheresis Treatment in Guillain–Barré Syndrome: Potential Benefit over IVIg in Patients with Axonal Involvement

Response to therapeutic plasma exchange (TPE) was evaluated in patients diagnosed with Guillain-Barré Syndrome (GBS). Our aim was to assess response to TPE in patients who had failed treatment with intravenous immune globulin (IVIg). We conducted a retrospective chart review of 10 patients with the diagnosis of Guillain-Barré Syndrome who required TPE. Patients were identified by reviewing data from log books for TPE at The University of Connecticut Health Center, Farmington CT, USA. Patients who had failed IVIg treatment prior to being referred for TPE were also identified. Eight out of 10 patients treated with TPE showed improvement in their neurological exam. Four patients had axonal involvement on electromyelogram (EMG). Three patients were referred for TPE after failing IVIg treatment. All three of these had axonal involvement on EMG. Three of the four patients with axonal involvement demonstrated improvement with TPE. TPE may be a superior treatment option as compared to IVIg in patients with GBS and EMG findings of axonal involvement.