Sessions Of Plasmapheresis Research Articles

Rituximab in the Treatment of Refractory Myasthenia Gravis: Studying the Outcomes Using MMT Score And Need for Plasmapheresis in Baghdad Teaching Hospital

Introduction: Myasthenia gravis (MG) is an uncommon autoimmune disease that is caused by acetylcholine receptor antibodies (AChRA) at the neuromuscular junction. Its pathogenesis involves complement fixing antibodies directed against acetylcholine receptors, muscle-specific tyrosine kinase or low density lipoprotein receptor–related protein. Method: A descriptive case series study investigating rituximab in refractory MG was conducted in Baghdad teaching hospital .Patients who were included in the study had received a regimen of rituximab that was deemed appropriate by their treating physician. Results: A total of 24 patients with mean disease duration of 6.3 years ±3.6 standard deviation were included in this study. The results showed that the average age of patients was 33.3 ,years ±10.1 SD and 62.5% was females. All twenty four patients showed an obvious improvement in clinical status after finishing the follow-up period. The results demonstrated from all patients that enrolled in our study, only one patient that who was on 14 sessions of plasmapheresis was in need for plasmapheresis after induction of rituximab and this difference was statistically significant. Conclusion: There were a great clinical improvement as shown with MMT score in addition to discontinuation of plasma exchange treatments fallowing treatment with rituximab.

Rituximab in the Treatment of Refractory Myasthenia Gravis : Studying the Outcomes using MMT Score and Need for Plasmapheresis in Baghdad Teaching Hospital

Introduction: Myasthenia gravis (MG) is an uncommon autoimmune disease that is caused by acetylcholine receptor antibodies (AChRA) at the neuromuscular junction. Its pathogenesis involves complement fixing antibodies directed against acetylcholine receptors, muscle-specific tyrosine kinase or low density lipoprotein receptor–related protein. Method: A descriptive case series study investigating rituximab in refractory MG was conducted in Baghdad teaching hospital .Patients who were included in the study had received a regimen of rituximab that was deemed appropriate by their treating physician. Results: A total of 24 patients with mean disease duration of 6.3 years ±3.6 standard deviation were included in this study. The results showed that the average age of patients was 33.3 ,years ±10.1 SD and 62.5% was females. All twenty four patients showed an obvious improvement in clinical status after finishing the follow-up period. The results demonstrated from all patients that enrolled in our study, only one patient that who was on 14 sessions of plasmapheresis was in need for plasmapheresis after induction of rituximab and this difference was statistically significant. Conclusion: There were a great clinical improvement as shown with MMT score in addition to discontinuation of plasma exchange treatments fallowing treatment with rituximab.

Treatment of Anti-HLA Donor-Specific Antibodies in Heart Transplantation: A Single-Center Experience

The presence of anti-HLA donor specific antibodies (DSA) after heart transplantation is associated with antibody-mediated rejection (AMR) and poor graft survival. Aim of this study was to present the results of our treatment protocol of DSA in heart transplantation. Since late 2016, at our institution, heart-transplanted patients with DSA but without graft dysfunction (Group 1) were treated with IgA- and IgM-enriched intravenous immunoglobulins (IgGAM) only (first infusion: 2g/kg, then 0.5g/kg once every 4 weeks for a maximum of 6 months). Patients with DSA and graft dysfunction (Group 2, clinical AMR) were treated with additional 5 sessions of plasmapheresis (PE) before IgGAM and a single a single dose of anti-CD20 antibody (Rituximab, 375mg/m2) after the first IgGAM infusion. Highly allosensitized (PRA>50%) patients showing preformed DSA (pfDSA), i.e. a positive virtual crossmatch (Group 3), were treated with an intraoperative single dose of the IL-6 receptor antibody Tocilizumab (10mg/kg), in addition to 5 sessions of PE, IgGAM infusions and a single Rituximab dose, as aforementioned. Among the 72 patients transplanted between 10/2016 and 10/2019, 3 (4%) patients formed Group 1, 8 (11%) patients Group 2, and 12 (17%) patients Group 3. Group 1 patients developed de novo DSA 31, 145 and 28 days after transplantation, were treated with IgGAM, which cleared DSA in all patients, were alive and did not show any episode of biopsy-confirmed rejection (ISHLT Grade R>1) at the end of follow-up. Group 2 patients developed de novo DSA at a median of 207 days after transplantation and showed graft dysfunction requiring ECMO support in 4 cases. Five (63%) patients died in-hospital. Among the 3 surviving patients, DSA were cleared in one patient. Group 3 patients showed pfDSA with >50% pre-transplant PRA. Post-transplant, patients did not show severe primary graft dysfunction, but one patient died in-hospital of pneumonia. pfDSA were cleared in 5 (42%) patients. At follow-up, all discharged patients survived, and 3 patients showed at least one episode of ISHLT Grade R>1 rejection or of minimal AMR (pAMR 1+). In heart transplantation, clinical AMR showed a dismal prognosis, despite treatment. Early diagnosis and preemptive treatment of DSA should be pursued. Transplantation across positive crossmatch barriers can be feasible and safe.

Impact on Outcome of Preoperative Plasmapheresis in Sensitized Lung Transplant Recipients

Presence of donor specific HLA antibodies (DSA) before lung transplantation may jeopardize the prognosis. Preoperative plasmapheresis (PP) for desensitization may improve graft outcomes but may have complications, mainly bleeding and infections. The primary objective of this study was to evaluate the efficacy of PP in term of level of DSA (micro fluorescent intensity (MFI)) and occurrence of antibody mediated rejection (AMR). Secondary outcomes included perioperative surgical revision, occurrence of pneumonia, and ICU mortality. We reviewed the charts of patients with preoperative DSA from 2015 to 2018. Patient's DSA were identified and followed by Luminex Single Antigen assay at three time points: before transplantation, in early (< 15 days) and late (up to 6 weeks) postoperative periods. PP was performed when MFI was >1,000 and was associated with an induction treatment. 3 sessions of postoperative plasmapheresis were performed when preoperative MFI was >3,000. Patients without PP represented control group. 205 patients were included, in whom 29 had PP (14%). During the predefined time frame, the kinetic of sum of DSA MFI did not differ between the two groups (ANOVA p=0.47) (Figure). Course of the highest MFI value seemed to stabilize in the PP group and differed from the control group (ANOVA p<0.005). They were no difference between the 2 groups in the occurrence of acute cellular rejection (38% vs 61%) or AMR (20% vs 17%). The PP group had more surgical revision in the first postoperative 48h (28% vs 10%; p=0.005). The incidence density rate of pneumonia was similar between the 2 groups (2.4±2.7 vs 3.1±4.7; p=0.11). ICU mortality rate was significantly higher in patients with PP (21% vs 8%; p=0.04). Our results suggested that PP stabilized the course of highest DSA and probably had an impact on the rate of episodes of AMR. However, the increase rate of surgical revision and ICU mortality rate suggested that such treatment should be used in selected patients.

The role of therapeutic plasmapheresis in patients with hyperthyroidism

BackgroundHyperthyroidism is characterized by excess hormone secretion from the thyroid gland. Anti-thyroid drugs (ATDs), surgery, and radioactive iodine can be used in treatment. Plasmapheresis is a rapid and effective treatment option in cases where rapid euthyroidism is needed to be obtained due to complications of thyrotoxicosis and major adverse effects of ATDs. Material and methodWe present patients receiving plasmapheresis to provide immediate euthyroidism due to severe hyperthyroidism, adverse effects of ATDs, or non-thyroid surgery from January 2012 to December 2016. ResultsThis study included 18 patients. The etiology of hyperthyroidism was TDG in seven patients, TDMNG in two, TA in two, TMNG in four, and one patient had AIT. Plasmapheresis was performed to achieve euthyroidism before surgery in two patients. The mean plasmapheresis session was 5.35. The mean number of sessions needed for patients with TDG and TDMNG was 4, whereas it was 6.5 for patients with TA and TMNG (p = 0.07). The decrease of mean free thyroxine and free triiodothyronine were 57 % and 73 %, respectively (p < 0.001). After plasmapheresis, total thyroidectomy was performed in 14 patients. Euthyroidism was achieved with RAI in one patient and with medical therapy in three patients. ConclusionsPlasmapheresis therapy is a reliable and effective treatment option for patients who cannot use ATDs because of their adverse events and those with hyperthyroidism that does not resolve with these drugs, or to achieve euthyroidism before total thyroidectomy, RAI or non-thyroid emergency surgery. However, it cannot be used widely because it is expensive and invasive.

SUN-317 INCIDENCE OF ACUTE REJECTION AND EARLY GRAFT LOSS AFTER KIDNEY TRANSPLANTATION IN A COHORT OF CHILDREN: A RETROSPECTIVE SINGLE CENTER STUDY

Acute rejection and delayed graft function are a common complication post kidney transplant that lead to significant number of graft failure. Our objective is to highlight the incident of acute rejection & delayed graft function after Kidney transplant in children, and its impact on allograft function. Abbreviations: congenital anomalies of the kidney and urinary tract (CAKUT); Donor Specific Antibody (DSA); donor/recipient (D/R); Antiyhymocyte Globulin (ATG); focal segmental glomerulosclerosis (FSGS); Intravenous immunoglobulin (IVIG); Kidney Transplantation (KTx); Polymerase chain reaction (PCR); complement dependent cytotoxicity (CDC); Human leukocyte antigen (HLA); A review of children underwent Kidney transplant between 2012 and 2019. Baseline demographics, Immunosuppression agents, episodes of acute rejection, delayed graft function and graft loss were collected. All children received induction therapy as Antiyhymocyte Globulin (ATG) to all high risk patient include all deceased kidney transplant and basiliximab induction for low risk patients. Tacrolimus and mycophenolate mofetil is a maintenance immunosuppression that given for all patient post kidney transplant. Table 1Age at Transplantation (years)Mean 10 yearsGenderMale 20 (60%)Weight (mean in Kilograms)21 kgNumber of Deceased donor23 (69.6%)Number of life related donor5 (15%)Number of unrelated life donor5 (15%)Mean Human leukocyte antigen (HLA) mismatches4.5/6Number of patients with zero Human leukocyte antigen (HLA) Matching7 (21.1%)Positive complement dependent Cytotoxicity (CDC) cross match12% (4patients)Anti-thymocyte globulin as induction87% (29 from 33 patients)Risk of acute Rejection9% (3 patients)Risk of Delayed graft function15% (5 patients)Donor Specific antibody was positive24% ( 8 patients)Mean cold time7 hoursCauses of End stage kidney disease(CAKUT) Congenital anomalies of the kidney and urinary tract12(36%)(FSGS) Focal Segmental Glomerulosclerosis7 (21.1%)Congenital nephrotic syndrome3 (9%)Wilms’ tumor1 (3%)Nephronophthisis1 (3%)UNKNOWN6 (18%) Open table in a new tab A total of 33 children were transplanted. Three episode of acute rejection (9%), two of them were acute cellular rejection that treated successfully with pulse of steroid and one episode were acute antibody rejection was treated with Intravenous immunoglobulin (IVIG) and multiple session of plasmapheresis. Five episode of delayed graft function (15%), one episode with graft failure related to thrombosis, Current immunosuppressant provide effective protection from renal allograft rejection, however there use may complicated by serious side effect.

The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation-A Single-Center Case Series.

Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.

A Case Report: First Ever ABO Incompatible Kidney Transplantation in Bangladesh: The Start of a New Era

Although ABO incompatible kidney transplantations are increasingly being practised worldwide, in Bangladesh it was never attempted. Here we report the first ever ABO incompatible kidney transplantation case performed in Bangladesh. The patient was a 23-year-old male with end-stage kidney disease secondary to chronic glomerulonephritis on haemodialysis. The only kidney donor available was his mother who had a different blood-group (patient O positive; mother A positive). His baseline anti-A IgG titre was 1:128. We used a modified desensitization protocol with low-dose Rituximab, triple immunosuppression (Tacrolimus, Mycophenolate Sodium and Prednisolone) and 3 sessions of plasmapheresis followed by IVIG. His Anti-A IgG titre was brought down to 1: 8 before transplantation. He also received basiliximab as induction therapy. He successfully underwent renal transplantation across the ABO barrier. After transplantation his IgG titre was monitored which was remained 1:4. At 1, 3 and 6 months of post transplant, serum creatinine level was 207 µmol/L, 182 µmol/L and 183 µmol/L, respectively. This was the first case of ABO-incompatible kidney transplantation in Bangladesh. This case gives us the confidence that more ABO-incompatible kidney transplantations can be performed in a resource limited setting and high infection risk countries like ours following a more cautious approach. This will substantially increase the living kidney donor pool; hence reduce the economic and health impact of continuing long term dialysis therapy in Bangladesh.

Acquired Combined Factor Deficiency: Case Report

Acquired hemophilia is a rare bleeding disorder. Difenacoum (superwarfarin), an antivitamin K anticoagulant, has been commonly used as a rodenticide. Factors II, VII, IX, and X are reduced as a result of this inhibition. In this article, we have presented a case that had been exposed to superwarfarin according to our consideration, but for which factor XII, VIII, XI, V deficiency and presence of inhibitor could not be explained. Coagulation tests of the patient who applied for hematuria were prolonged. Factor II, V, VII, VIII, IX, X, XI, XII were low; antinuclear antibody, antiphospholipid antibody IgG, and anti-double stranded DNA antibodies were positive. When questioned, he admitted that they used rat poison in the bakery. In addition to fresh frozen plasma, vitamin K and plasma complex concentrate, factor VIII and factor IX were started. However, sufficient response could not be obtained since there were inhibitors against factor VIII and factor IX. Three sessions of plasmapheresis were performed to clear antibodies and immunosuppressive treatment was started. While coagulation tests were still long, there was no new bleeding and hematuria stopped. Immunosuppressive treatment and plasmapheresis may be tried if the replacement of deficient factors is not sufficient in acquired factor deficiency.

Plasmapheresis Reduces Mycophenolic Acid Concentration: A Study of Full AUC0-12 in Kidney Transplant Recipients.

Background: Mycophenolic acid (MPA), a crucial immunosuppressive drug, and plasmapheresis, an effective immunoreduction method, are simultaneously used for the management of various immune-related diseases, including kidney transplantation. While plasmapheresis has been proven efficient in removing many substances from the blood, its effect on MPA plasma levels remains unestablished. Objectives: To evaluate the full pharmacokinetics of MPA by measuring the area under the time–concentration curve (AUC0–12), which is the best indicator for MPA treatment monitoring after each plasmapheresis session, and to compare the AUC0–12 measurements on the day with and on the day without plasmapheresis. Methods: A cross-sectional study was conducted in kidney transplantation recipients who were taking a twice-daily oral dose of mycophenolate mofetil (MMF, Cellcept®) and undergoing plasmapheresis at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, during January 2018 and January 2019. The MPA levels were measured by an enzymatic method (Roche diagnostic®) 0, 1/2, 1, 2, 3, 4, 6, 8, and 12 h after MMF administration, for AUC0–12 calculation on the day with and on the day without plasmapheresis sessions. Plasmapheresis was started within 4 h after administering the oral morning dose of MMF. Our primary outcome was the difference of AUC0–12 between the day with and the day without plasmapheresis. Results: Forty complete AUC measurements included 20 measurements on the plasmapheresis day and other 20 measurements on the day without plasmapheresis in six kidney transplant patients. The mean age of the patients was 56.2 ± 20.7 years. All patients had received 1000 mg/day of MMF for at least 72 h before undergoing 3.5 ± 1.2 plasmapheresis sessions. The mean AUC on the day with plasmapheresis was lower than that on the day without plasmapheresis (28.22 ± 8.21 vs. 36.79 ± 10.29 mg × h/L, p = 0.001), and the percentage of AUC reduction was 19.49 ± 24.83%. This was mainly the result of a decrease in AUC0–4 of MPA (23.96 ± 28.12% reduction). Conclusions: Plasmapheresis significantly reduces the level of full AUC0–12 of MPA. The present study is the first to measure the full AUC0–12 in MPA-treated patients undergoing plasmapheresis. Our study suggests that a supplementary dose of MPA is necessary for patients undergoing plasmapheresis.

Graves disease-induced thrombotic thrombocytopenic purpura: a case report

BackgroundThrombotic thrombocytopenic purpura is an autoimmune disease that carries a high mortality. Very few case reports in the literature have described a relationship between Graves disease and thrombotic thrombocytopenic purpura. We present a case of a patient with Graves disease who was found to be biochemically and clinically hyperthyroid with concurrent thrombotic thrombocytopenic purpura.Case presentationOur patient was a 30-year-old African American woman with a history of hypertension and a family history of Graves disease who had recently been diagnosed with hyperthyroidism and placed on methimazole. She presented to our hospital with the complaints of progressive shortness of breath and dizziness. Her vital signs were stable. On further evaluation, she was diagnosed with thrombotic thrombocytopenic purpura, depending on clinical and laboratory results, and also was found to have highly elevated free T4 and suppressed thyroid-stimulating hormone. She received multiple sessions of plasmapheresis and ultimately had a total thyroidectomy. The patient’s hospital course was complicated by pneumonia and acute respiratory distress syndrome. Her platelets stabilized at approximately 50,000/μl, and her ADAMTS13 activity normalized despite multiple complications. The patient ultimately had a cardiac arrest with pulseless electrical activity and died despite multiple attempts at cardiopulmonary resuscitation.ConclusionGraves disease is an uncommon trigger for the development of thrombotic thrombocytopenic purpura, and very few cases have been reported thus far. Therefore, clinicians should be aware of this association in the appropriate clinical context to comprehensively monitor hyperthyroid patients during treatment.

Systemic lupus erythematosus with the development of neuromyelitis optica (Devic's syndrome) is a rare combination of autoimmune diseases

Neuromyelitis optica ((NMO), Devic's syndrome) is an immune-mediated inflammatory demyelinating disease characterized by transverse myelitis and optic neuritis. Determination of the level of antibodies to aquaporin 4 (NMO-IgG) is presently one of the key methods for the diagnosis and assessment of the activity of ONM, which allows this disease to be differentiated from multiple sclerosis and other demyelinating CNS lesions. ONM can occur not only as an independent disease, but also as a syndrome in different systemic diseases, such as: systemic lupus erythematosus (SLE), antineutrophilic cytoplasmic antibody-associated vasculitides, Sjögren's disease, etc. (up to 50–70%). In such situations, the clinician is always confronted with a question as whether the patient can have two rare autoimmune diseases or develop ONM as a systemic manifestation of rheumatic disease.The paper describes a clinical case of a young female patient with SLE concurrent with a CNS lesion, the manifestations of which corresponded to ONM. The patient had focal changes in the substance of the brain and spinal cord, as evidenced by magnetic resonance imaging, as well as high NMO-IgG titers. The development of ONM worsens SLE prognosis and requires active immunosuppressive therapy. The patient received three plasmapheresis sessions, ultrahigh-dose glucocorticoid and cyclophosphamide therapy, followed by replacement with azathioprine, causing a stable clinical and laboratory disease remission to be achieved.

DIFFUSE ALVEOLAR HEMORRHAGE AND EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO): A BLOODY CONUNDRUM

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Diffuse alveolar hemorrhage (DAH) may mimic Acute Respiratory Distress Syndrome (ARDS) and is associated with high mortality. Veno-venous ECMO has proven to be valuable in the treatment of ARDS. Anticoagulation in the setting of DAH is challenging. We present a case of DAH successfully treated with ECMO without anticoagulation. CASE PRESENTATION: A 64-year-old female with minimal past medical history and recent sinusitis was admitted to our facility after being cannulated and placed on ECMO due to worsening ARDS despite paralysis and prone positioning. She was noted to be anemic and urine analysis revealed red blood cell (RBC) casts and dysmorphic RBCs, therefore, bronchoscopy with bronchoalveolar lavage was performed and revealed significant bloody aliquots. Further laboratory investigations revealed positive C-ANCA and PR3 suggestive of Granulomatosis with Polyangiitis (GPA). She was initially placed on bivalirudin, however due to severity of DAH and cannula site bleeding, the decision was made to stop anticoagulation. ECMO was maintained at high flow, 4.2 L/min. and the circuit was switched to a heparin coated system. GPA targeted treatment included Methylprednisolone 1gm/day for 3 days followed by an 8-week taper, IV cyclophosphamide, and 7 sessions of plasmapheresis. She was weaned off ECMO on day 9. With exception of minor oxygenator clots which did not interfere with efficacy of ECMO, there were no complications from absence of systemic anticoagulation. She was liberated from mechanical ventilation on day 27 and discharged to rehabilitation facility. There, she was decannulated and no longer requiring supplemental oxygen. DISCUSSION: Historically, inability to use anticoagulation has been viewed as a relative contraindication to ECMO. There are successful cases of ECMO therapy in DAH attributed to targeting lower activated clotting times. It’s well known that ECMO bleeding complications due to anticoagulation are common and can drastically alter desired outcomes. Advances in the ECMO circuit, now coated with heparin and maintaining high flow allow prolonged ECMO runs without anticoagulation in those with a risk of bleeding. Our patient was able to successfully complete a 9-day ECMO run using the above strategy. CONCLUSIONS: Our case demonstrates the importance of keeping DAH as a differential causing ARDS and ability to provide supportive care with ECMO while curative treatments for DAH are implemented. It also demonstrates relative safety of not using systemic anticoagulation for a prolonged period with the use of high flow through a heparin coated ECMO circuit. Careful monitoring for thrombotic complications is necessary when the above approach is used. Despite the lack of guidelines for this patient population, it’s of great importance that treating clinicians have a low threshold to seek advice and refer to an ECMO center, as its use can dramatically improve the clinical outcome. Reference #1: Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL. et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicenter randomized controlled trial. Lancet. 2009;374(9698):1351–1363. Reference #2: Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018;378(21):1965-1975. Reference #3: Simpson T, Ling C, Glover G, Barrett N, Ioannou N, Lams B, Langrish C, Meadows C, Agarwal N, D’Cruz D. P278 Extra-corporeal membrane oxygenation and diffuse alveolar haemorrhage – a single centre case series and analysis of the ELSO database. Thorax 2014;69: A195–A196. DISCLOSURES: No relevant relationships by Evan Gajkowski, source=Web Response No relevant relationships by Alejandra Garcia Fernandez, source=Web Response No relevant relationships by Yatin Mehta, source=Web Response No relevant relationships Added 02/27/2019 by Kenneth Snell, source=Web Response, value=Grant/Research Support Removed 03/06/2019 by Kenneth Snell, source=Web Response

Steroid resistant recurrent transverse myelitis in an elderly female with good response to plasma pheresis: A case report

Transverse myelitis is a rare disease involving inflammation of the spinal cord. It is estimated to have an incidence of 1.34 to 4.6 per million. It is more common in females and has a bimodal peak at 10–19 years old and 30–39 years old. It is monophasic but may become recurrent in some. Diagnostic criteria for the spectrum of diseases involving transverse myelitis is still evolving. Studies have shown an association between recurrent transverse myelitis, neuromyelitis optica spectrum and autoimmune antibodies associated with systemic lupus erythematosus (SLE) and other systemic autoimmune conditions. Management options for recurrent transverse myelitis include steroids, plasmapheresis, immunosuppressive antimetabolites and monoclonal antibody. We are presented now with an interesting case of recurrent transverse myelitis in an elderly female presenting with progressive weakness and numbness of the bilateral lower extremities. She tested positive for autoimmune antibodies anti-ssA and anti-dsDNA. She had disease progression despite management with intravenous steroids, hence was considered steroid-resistant. The patient responded well with six sessions of plasmapheresis.

GRANULOMATOSIS WITH POLYANGIITIS PRESENTING AS BILATERAL DIFFUSE ALVEOLAR HEMORRHAGE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Granulomatosis with Polyangiitis (GPA) most commonly occurs in older adults with multi-organ involvement including skin, kidneys and respiratory tract. Some of the pulmonary complications include dyspnea, small airway obstruction, pulmonary infiltrates, cavitary lesions and rarely, pulmonary hemorrhage. We present a case diffuse alveolar hemorrhage (DAH) as the initial presentation of GPA. CASE PRESENTATION: 57-year-old African American female with history of hypertension, diabetes mellitus, ductal carcinoma in situ, ischemic stroke, tobacco abuse and obesity presented with cough, progressive dyspnea and mild hemoptysis. On pulmonary examination, she had labored breathing and expiratory wheezes. Initial laboratory examinations were all within normal limits. A chest radiograph showed diffuse bilateral infiltrates. A high-resolution computed tomography of her chest revealed diffuse bilateral alveolar infiltrates with sparing of the lung peripheries and bases with confluent ground glass nodularity. She was empirically started on intravenous methylprednisolone and oral levofloxacin. Due to worsening respiratory symptoms and increased oxygen requirements, she was intubated. Bronchoscopy revealed bilateral alveolar hemorrhage across four dilutions. Bronchoalveolar lavage was negative for bacterial growth. Video-assisted thoracoscopic surgery (VATS) wedge biopsy showed diffuse neutrophilic inflammation, without evidence of granuloma or vasculitis. Plasmapheresis was initiated. She was successfully extubated after three sessions of plasmapheresis. Rheumatological workup returned positive for PR3 antibody. She was sarted on Rituximab for presumed GPA. She was discharged to a nursing facility. On a subsequent admission 10 days later, she was diagnosed with rapidly progressive glomerulonephritis, confirmed on renal biopsy. A skin lesion biopsy showed retiform purpura with ulcerations, consistent with medium and small vessel vasculitis. She was transitioned from rituximab to induction with cyclophosphamide and plasmapheresis was continued until she was stable and discharged back to nursing facility. DISCUSSION: This is an unfortunate but interesting initial presentation of GPA with mild hemoptysis and dyspnea resulting in alveolar hemorrhage, a rare complication of GPA. In addition, her renal involvement contributes to a worse prognosis with an estimated 10-year survival rate of 40%. CONCLUSIONS: GPA is a necrotizing systemic vasculitis that involves multiple organs, most commonly affecting skin, kidneys and lungs. However, these organs can have an array of symptoms that pose a difficulty in recognizing the disease, therefore, requiring a high clinical suspicion. DAH is a rare and life-threatening complication of GPA. Some clues to further explore DAH would include hemoptysis, dyspnea, anemia and hypoxia. Early diagnosis and initiation of treatment is important to preventing morbidity and mortality. Reference #1: Greco A, Marinelli C, Fusconi M, et al. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2015;29(2):151-9. Reference #2: West S, Arulkumaran N, Ind PW, Pusey CD: Diffuse alveolar haemorrhage in ANCAassociated vasculitis. Intern Med 52: 5–13, 2013 DISCLOSURES: No relevant relationships by Kylee Dawson, source=Web Response No relevant relationships by Navneet Kaur, source=Web Response No relevant relationships by Sowjanya Yenigalla, source=Web Response

TREATMENT OF ACUTE BUPROPRIONE TOXICITY WITH LIPID INFUSION AND PLASMAPHERESIS

SESSION TITLE: Plasmapheresis to the Rescue SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/21/2019 3:15 PM - 4:15 PM INTRODUCTION: Bupropion is an atypical antidepressant used to treat major depressive disorder and other psychiatric conditions. The toxic side effects of bupropion include seizures, tachycardia, arrhythmias, and death. These side effects are dose and formulary dependent. We describe a case of acute bupropion toxicity from a suicide attempt with symptoms, which was treated with Intralipid infusion along with serial plasmapheresis. CASE PRESENTATION: A 19-year-old male was transferred from an outside hospital for suicide attempt with ingestion of 40 tablets of 150 mg sustained released (SR) bupropion for a total dose of 9 gm. He was not a candidate for any activated charcoal. The patient developed tonic-clonic seizures and the decision was made to initiate a bolus of 140 mL of 20% Intralipid before and during transport. On admission to our hospital he developed status epilepticus and had QTc prolongation (467 and 487). He was started on 800 mL lipid infusion immediately followed by serial plasmapheresis. The triglyceride levels were closely monitored. The patient received a total of 940 mL (140 mL bolus plus 800 mL continuous infusion) of intralipid along with 3 sessions of plasmapheresis. He remained seizure free and his QTc normalized and was successfully extubated. DISCUSSION: Bupropion is a highly lipid soluble and protein-bound medication. Mild toxicity includes dry mouth, nausea, insomnia, dizziness. Life-threatening toxicities include seizure and arrhythmias. Seizures are generally seen with an overdose of bupropion. Ingestion of 4.5-9 g of bupropion increases the likelihood of seizures. Treatment is mostly symptomatic and with benzodiazepines. Lipid infusions can be used as lipid rescue therapy for acute cardiovascular collapses. The mechanism is the same as the use of lipid infusion as rescue therapy in case of local anesthetic, tricyclic antidepressants or serotonin-specific reuptake inhibitor toxicities. The proposed mechanism involves lipids from the infusion binding to the offending drug and pulling it from the target tissue preventing its accumulation and minimizing the toxic effects. Despite several reports there seem to be increased risks and compilations associated with lipid infusions like acute respiratory distress syndrome, hypertriglyceridemia, pancreatitis, and cardiac toxicity. There are not many reports of the use of plasmapheresis in a timely manner (depending on the half-life of the drug) for an SR drug after lipid infusion to promote removal of all the lipid molecules including those bound to the offending drug thereby preventing toxicity from the drug and lipid infusion as well. In our case combination of both helped in stabilizing and treating the patient. CONCLUSIONS: Use of lipid infusion in conjugation with plasmapheresis for the treatment of acute bupropion toxicity with symptoms allows safe use of lipid infusion and ensures complete removal of offending drug. Reference #1: Tolentino Stephanie; Gharpure, Varsha; Tsifansky, Michael Critical Care Medicine: December 2013 Reference #2: Intravenous lipid emulsion in clinical toxicology Leelach Rothschild,corresponding author1 Sarah Bern,1 Sarah Oswald,1 and Guy Weinbergcorresponding author1,2 DISCLOSURES: No relevant relationships by Praful Tewari, source=Web Response

Experience of using polymethyl methacrylate membranes for anti-HLA antibodies’ elimination by hemodialysis in renal transplant recipients

Introduction. In recipients with pre-existing sensitization with incompatible antigens of the main histocompatibility complex, the kidney graft survival after retransplantations directly depends on the level of anti-HLA antibodies. Despite many years of experience in using various methods: plasmapheresis, cascade filtration, immunosorption, intravenous administration of immunoglobulins, the use of polyclonal anti-lymphocytic agents, the search for more acceptable ways to reduce the level of anti-HLA antibodies still remains relevant nowadays.The purpose of the study was to assess the effect of polymethyl methacrylate membrane-based dialyzers on the decrease in anti-HLA antibody level in renal transplant recipients.Material and methods. The study included 20 kidney transplant recipients. The main study group consisted of 10 patients who underwent early postoperatoive hemodialysis using polymethyl methacrylate membrane-based dialyzers to decrease anti-HLA antibody level. A total of 53 hemodialysis procedures were performed, an average of 5.3 per patient. The comparison group included 10 recipients in whom plasmapheresis had been performed at similar timing after kidney transplantation aimed at reducing the anti-HLA antibody titers and whose data were studied retrospectively. A total of 38 plasmapheresis sessions were performed, an average of 3.8 per patient.Results. In the main study group, a day after the hemodialysis procedure using polymethyl methacrylate membranebased dialyzers the level of anti-HLA antibodies decreased by an average of 28.3% in 6 of 10 patients (60%), and increased in 4 cases. Meanwhile, in the comparison group, the level of anti-HLA antibodies in venous blood after a plasmapheresis session decreased average by 44.6% in 8 patients of 10 (80%), and increased in 2 cases, on the contrary. Of note, there were no significant differences between the patients of the two compared groups either in the number of positive results (p&gt; 0.05, Fisher's exact test), or in terms of the decrease in anti-HLA antibody level (p&gt; 0.05, Mann – Whitney test). On days 2 and 5, in 50% of cases both after the hemodialysis procedure using polymethyl methacrylate membranebased dialyzers and after the plasmapheresis session, the patients showed an increase in the anti-HLA antibodies level compared to the baseline values. In the remaining cases, the level of anti-HLA antibodies in both groups was recorded at a lower range compared to the baseline values.Conclusion. The use of polymethyl methacrylate membrane-based dialyzers in the renal allograft recipients having a high level of preexisting anti-HLA antibodies seems promising for the period of oligoanuria until the renal allograft function is restored, since both hemodialysis and the sorption of pre-existing (and also newly synthesized) antibodies take place simultaneously.

Successful Heartmate 3 LVAD Implantation in a Patient with Heparin Induced Thrombocytopenia Using Pre-Implantation Plasmapheresis and Intraoperative Continuous Prostacyclin

Introduction Heparin Induced Thrombocytopenia (HIT) describes a prothrombotic state with significant rates of thrombus formation. We present a rare case of successful implantation of a HeartMate 3 left ventricular assist device (LVAD) in a patient with HIT using pre-transplant plasmapheresis followed by intraoperative prostacyclin administration. Case presentation A 48-year-old male with history of three vessel CAD and ischemic cardiomyopathy presented with symptoms of shortness of breath. Initial plans for CABG were cancelled given critically low ejection fraction of 15%, lack of myocardial viability and moderate to severe mitral regurgitation. He was subsequently evaluated for surgical AHF therapies. In pre-transplant testing, platelets were 296. An intra-aortic balloon pump was placed for hemodynamic optimization with peri-procedural heparin utilization. Shortly thereafter, his platelets fell to 136. HIT was suspected by ELISA testing with initial optical density (OD) of anti- platelet factor 4 (PF4) of 1.255, confirmatory testing with serotonin release assay was positive at 87%. Anticoagulation was switched to argatroban. Due to clinical deterioration, urgent LVAD implantation was planned. He underwent five sessions of plasmapheresis (PP) every other day to reduce circulating PF4 antibodies prior to implantation (Figure). PP sessions included replacement of total plasma volume with 5% albumin followed by saline over two hours. Anti-PF4 OD levels decreased to 0.987 following first session. Subsequent levels fell to 0.570, 0.348 and 0.153 following the second, third and fourth sessions. He underwent his fifth session of plasmapheresis during Heartmate 3 LVAD implantation. A continuous infusion of epoprostenol starting at an infusion of 15 ng/kg/min was initiated 30 minutes before intra-operative heparin administration and titrated to a dose of 30 ng/kg/min. Epoprostenol was discontinued 15 minutes after protamine reversal at the conclusion of the case. Post-operative Anti-PF4 levels were 0.114. He developed DIC with INR 4.1, PT 39.7, PTT 107.4 and Fibrinogen 70 following implantation requiring Factor 7 administration. The patient is doing well 3 months post-LVAD implantation and is being considered for heart transplantation. Discussion HIT can be a barrier to advanced surgical AHF therapies. Pre-implantation plasmapheresis followed by intraoperative continuous prostacyclin administration is an effective and safe method to reduce anti-PF4 levels and platelet activation and thus the risk of thrombosis.

Plasmapheresis Effect on Hematological and Biochemical Parameters in Athletic Horses Subjected to Exercise

To evaluate the effect of plasmapheresis on clinical, hematological, and biochemical parameters after exercise, a plasmapheresis session was realized on six jumping horses (plasmapheresis group) that underwent three consecutive days of physical graded exercise. The control group (n = 6) went through the same exercise but not subjected to the plasmapheresis session. Seventeen milliliters of plasma/kg of body weight was harvested from each horse. The procedure was well tolerated by the horses. The plasmapheresis leads to a significant increase of the hemoglobin, hematocrit, red blood cell, white blood cell, and lymphocytes counts. Plasmapheresis induced a very significant decrease (P < .001) of albumin and globulin levels and of total protein, which were reestablished 24 hours later. Plasmapheresis also generated a very significant increase (P < .001) in sodium levels and a significant decline of potassium (P < .05) and calcium (P < .01) levels. Several other biochemical variables remained unchanged. Results also showed that, after a significant rise of lactate, aspartate aminotransferase, and creatine kinase levels which are subsequent to the exercise, the plasmapheresis session induced a very significant continuous decrease (P < .001) of these parameters. The present work has demonstrated that the plasmapheresis is able to modify the physiology after exercise and to affect both the hematology and the biochemistry of the blood hematobiochemical parameters in horses subjected to physical exercise.

Favorable Outcome of an Exclusively Posttransplant Prophylactic Strategy After Heart Transplantation in Recipients With High Immunological Risk.

Management of the increasing number of sensitized heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitization therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy. A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/- perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (AMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our center. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection, and cardiac allograft vasculopathy-free survival. A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500 to 1000 and greater than 1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of antibody-mediated rejection. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells. This exclusively posttransplant prophylactic strategy achieved favorable outcomes in heart transplant recipients with pfDSA.