Sessions Of Plasmapheresis Research Articles

Blood is always thicker than water – A case of renal involvement in waldenstrom's macroglobulinemia

A 41-year-old man presented with nonspecific complaints of nausea, vomiting, and generalized fatigue for 2 months. He had renal dysfunction and severe anemia, for which he underwent acute peritoneal dialysis and four packed red blood cell transfusions at another hospital. Sampling his blood for laboratory evaluation was difficult as the sample would repeatedly clot before the machine could assess the same. It was found that the patient had hyperproteinemia, with hyperviscosity which was causing the same. Further evaluation revealed a monoclonal gammopathy, which was IgM predominant, and bone marrow evaluation revealed Waldenstrom’s macroglobulinemia (WM). Renal biopsy also showed light-chain cast nephropathy. The patient underwent three sessions of plasmapheresis and was initiated on chemotherapy and showed symptomatic and laboratory improvement. This case reveals renal involvement in WM, which is rare and highlights the difficulty faced in evaluating the plasma samples of the patient for laboratory investigations.

Postpartum Acquired Hemophilia (PAH) – A Rare Entity

Objective: Acquired Hemophilia A (AHA) is a rare autoimmune disease that can result in life threatening bleeding. Formation of auto-antibodies (inhibitors) against coagulation factor VIII develops the hemorrhagic syndrome that may appear at any age; however, prevalence of AHA is chiefly observed in post-partum and elderly persons. Idiopathic acquired hemophilia is commonest type of acquired hemophilia whereas it is also associated with autoimmune disease, malignant neoplasm, medication and vaccinations. Post-partum acquired hemophilia (PAH) may develop due to development of antibodies against fetal FVIII. In this case report, 36-year-old Asian woman presented with complain of bruises from 2 months. There was history of cesarean section four months ago. Family history, past medical and drug history were not significant. As there was no active bleeding, patient was started an oral prednisolone along with azathioprine and was counseled regarding disease and precautions. Patient presented after 2 weeks with severe PV bleed, anemia secondary to self-induced medicine abortion. For this she receives pack cells and cryoprecipitate. Steroids and azathioprine were continued and patient was discharged in stable condition. Her ultrasound pelvis however showed small fibroids. Patient went back to her village where she again develops severe PV bleed and for that she underwent hysterectomy. Patient presented in our hospital with severe operative site bleeding, pain and anemia. She was managed with Packed Red Blood (PRBCs), Fresh Frozen Plasma (FFP), Recombinant Activated Clotting Factor VII (rFVIIa), prednisolone IV and azathioprine PO. Her Activated Partial Thromboplastin, Hemoglobin were continuously monitored. After a week bleeding was stopped but Activated Partial Thromboplastin Time (APTT) was still prolonged so we tapered rFVIIa dose and advice two sessions of plasmapheresis. APTT, hemoglobin levels, inhibitor titer, High-Sensitivity C – reactive protein (hs-CRP) levels were improved. Patient was discharged in a stable condition and was advised to continue medication at home with supportive care and wound dressing.

Late Onset of Pneumocystis jirovecii Pneumonia in Kidney Transplant: How Long is too Long in Opportunistic Infection Prophylaxis?

Pneumocystis jirovecii (PJ) opportunistic infections occur in immunocompromised patients impacting significantly hospitalizations and mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) is universally used as prophylaxis of Pneumocystis jirovecii pneumonia (PJP) and therefore, this infection is rare condition in solid organ transplant (SOT) recipients. We present a case of a 46-years-old male, who received an ABO-incompatible transplant with prior desensitization protocol with plasmapheresis, rituximab, and anti-CMV immunoglobulin. IgG anti-B title pre-desensitization was 1:128. The patient had 6 ABDR mismatches, without HLA antibodies, and the CDC crossmatch for T and B cells was negative. Both recipient and donor were CMV positive (D+/R+). The patient received induction immunosuppression with corticosteroids, basiliximab, calcineurin inhibitor, and mycophenolate mofetil. Immediate kidney function was verified, and three additional plasmapheresis sessions were performed. At discharge serum creatinine (sCr) was 1.38 mg/dL, but kidney function declined during the first 6 months (sCr 2.5 mg/dL). Urinalysis was unremarkable. A kidney biopsy was declined by the patient. Unit protocol maintained the prophylaxis for PJP and cytomegalovirus (CMV) infection with TMP-SMX and valganciclovir. The patient was admitted to the emergency department 20 months after the transplant with respiratory symptoms and was diagnosed with PJP. Bronchoalveolar lavage fluid was also positive for CMV. Intensive care unit (ICU) admission was necessary due to clinical deterioration, with subsequent good evolution without mechanical ventilation. At discharge, prophylaxis with TMP-SMX and valganciclovir was maintained for more than six months. Here we discuss the late onset of PJP, and the main risk factors related to severe infection. Transplant subgroups in which longer PJP prophylaxis could be beneficial and the indication to re-start PJP prophylaxis is still under discussion.

207: SEPTIC CHRONIC PULMONARY THROMBOEMBOLIC DISEASE RESCUED BY VA ECMO AND THROMBOENDARTERECTOMY

Introduction: We report the case of a man with chronic thromboembolic pulmonary hypertension (CTEPH) who developed mixed shock from a unique source and required veno-arterial extracorporeal membranous oxygenation (VA ECMO) for refractory cardiopulmonary failure. Description: A 19-year-old man with asthma and progressive dyspnea presented to an outside hospital after developing spontaneous pneumomediastinum. Computed tomography (CT) chest showed coarse calcifications in the right pulmonary artery (RPA) and lung nodules concerning for malignancy. Initial evaluation was consistent with CTEPH and antiphospholipid antibodies. PET scan and cardiac MRI confirmed thrombus. Endobronchial ultrasound (EBUS) and biopsy were then performed. The patient was transferred to our center for surgical pulmonary thromboendarterectomy (PTE). On hospital day (HD) 2, he acutely decompensated with tachycardia, hypoxemia, hypotension, and rigors. Broad-spectrum antibiotics, vasopressors, and non-invasive positive pressure ventilation (NIPPV) were started. He developed worsening hypoxemia and shock and was cannulated with VA ECMO, which rapidly improved his hemodynamics and oxygenation. He was quickly liberated from vasopressors and NIPPV. CT pulmonary angiography showed new foci of gas within the RPA clot, and blood cultures grew Streptococcus mitis and Granulicatella adiacens. Hypercoagulability evaluation revealed warm and cold agglutinins. After two sessions of plasmapheresis, he underwent PTE on HD 7. Purulence was noted around the RPA thrombus. Following successful PTE, he separated from cardiopulmonary bypass and ECMO. He liberated from vasopressors and inotropes and extubated on postoperative day (POD) 1. RPA fluid culture grew Actinomyces odontolyticus. He was discharged on POD 14. At 3-month follow-up, he had less dyspnea and no serious complications. Discussion: Patients with CTEPH have a high risk of acute right ventricular (RV) failure from worsening pulmonary hypertension or RV ischemia from systemic hypotension (e.g., sepsis). In this case, it is likely that biopsy of the RPA thrombus introduced bacteria, leading to bacteremia, septic shock and rapid hemodynamic collapse. VA ECMO was a successful rescue therapy, minimizing the need for escalating vasopressors and PPV, which may worsen RV dysfunction.

Efferent therapy in pregnant women with the threat of very early premature birth with premature effusion of amniotic fluid. Two clinical observations

It is known from the literature that premature amniotic fluid expulsion in 22 weeks 27 weeks 6 days gestation is very dangerous, as it is accompanied by high morbidity and mortality in newborn infants.
 Clinical observation. This article presents the results of observing two women with premature amniotic fluid expulsion at 22 and 24 weeks gestation, respectively. In the first case, the woman was immediately admitted to the perinatal center; in the second observation, she was admitted after 3.5 weeks of treatment at another institution. In both cases, pregnant women had manifestations of oligo and endotoxemia, a protective inflammatory response in the mother-placental-fetal system (more pronounced in the second observation) against a background of urogenital infection. In the course of complex treatment, the patients underwent detoxification, of efferent therapy in the form of repeated consecutive sessions of plasmapheresis, hemosorption (one operation each), external photomodification of blood with ultraviolet, laser beams with prolongation of pregnancy by 10 and 8 weeks. The deliveries in both cases were operative with live babies with body weight of 1600 g and 1840 g, respectively. In the first case the infant did not need intensive care, was breastfed, in the second observation the newborn received active respiratory support for 9 days, in the dynamics his condition normalized. No septic complications in mothers and fetuses were observed.
 The concluding efferent therapy in course of therapy were effected by prolongating of pregnancy with of good the results for mothers and them of fetus.

Effect of ABO Mismatch and RBC Alloimmunization on the Outcomes of Patients with Sickle Cell Disease Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoietic stem cell transplantation (HSCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Non-myeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. Methods: We conducted a retrospective analysis of all adolescents and adult SCD patients (age >14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized stem cells targeting 10x106 /kg of CD34 cells were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was > 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer < 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis. Results: A total of 194 patients were included with a median age of 26 years and 55.6% being males. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.57% of patients, CNS disease in 19.58%, and acute chest syndrome in 17.01%. Other indications included sickle nephropathy, sickle hepatopathy, priapism and AVN in 10.82% of patients collectively. Around 59% of donors were sickle cell disease carriers, and 41% were healthy donors. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis (table 1a), ABO minor incompatibility (odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13 -11.65, P=0.029, and RBC alloantibodies against donor non-ABO antigens (OR, 4.22; 95% CI, 1.17 -15.14, P=0.039) were predictive for GF. However, on multivariate analysis (table 2a), only RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The median OS for patients with GF was 98% compared to 74% patients without GF, P<0.0001) (Figure 1). Conclusion: In our SCD transplanted patients, RBC alloantibodies against donor non-ABO antigens was an independent risk factor for GF. Patients with GF had an inferior survival and strategies for decreasing the risks are needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ODP149 Hypertriglyceridemia-Induced Acute Pancreatitis in Second Trimester of Pregnancy

Abstract Background Acute pancreatitis (AP) during pregnancy is a rare, potentially life-threatening disease, with an incidence of 1 case per 1,000-10,000. Hypertriglyceridemia (HTG)-induced pancreatitis accounts for only 5% of cases. Here we describe a rare case of HTG-induced AP during the second trimester of pregnancy, which was treated with concurrent insulin and plasmapheresis. Clinical Case A 35-year-old multigravida female was admitted for preterm premature rupture of membranes at 26 weeks gestation. Symptoms began on day 8 of admission and included severe epigastric pain radiating to the back. On exam, there was significant epigastric tenderness on palpation. There were no xanthelasmas or tendon xanthomas seen. She was afebrile but tachycardic. Laboratory evaluation noted a triglyceride (TG) level of &amp;gt;5,680 mg/dL (n&amp;lt;150), amylase 201 U/L (n&amp;lt;100) and lipase 277 U/L (n&amp;lt;60), consistent with AP. She was euglycemic. CT of the abdomen showed interstitial edematous pancreatitis with a peripancreatic collection. She was placed on NPO and started on intravenous (IV) fluid therapy, in combination with IV insulin and 10% dextrose. The patient also underwent one session of plasmapheresis. TG levels downtrended rapidly to 3,585 mg/dL within 24 hours. Once TG levels decreased below 1,000 mg/dL, insulin and dextrose infusions were stopped, and combination therapy of fenofibrate, omega-3 fatty acids, and low-fat low-carbohydrate diet was started. At 28 weeks and 5 days gestation, a cesarean section was performed due to suspected fetal distress. The patient was discharged on fenofibrate and Omega-3 fatty acids with a TG level of 456 mg/dL. Genetic testing revealed a heterozygous variant in the LPL gene mutation (c.644G&amp;gt;A; p. Gly215Glu) and a heterozygous variant of uncertain significance (VUS) in the ABCA1 gene (c.1765G&amp;gt;A; p. Val589Ile). She had no known family history of hyperlipidemia or cardiovascular disease. Conclusion Lipoprotein lipase (LPL) deficiency is an autosomal recessive disorder caused by biallelic pathogenic mutations in the LPL gene. The heterozygous c.644G&amp;gt;A variant has been previously described in several patients with LPL deficiency, however its impact on the function of the LPL protein has not yet been clearly defined. The ABCA1 gene is associated with Tangier disease, characterized by very low HDL levels and HTG. The ABCA1 gene variant detected in this case is classified as VUS as its effect on the gene function is not yet known. Further investigation is warranted to understand the role of these variants in familial dyslipidemia. Aside from the described patient, only one other case report of HCT-induced AP treated with concomitant plasmapheresis and IV insulin therapy has been reported in the literature. There are no published guidelines regarding the optimal treatment for HTG-induced AP in pregnancy. Combined treatment modality with plasmapheresis and IV insulin seems to be effective, however, its risks and benefits should be carefully assessed. Presentation: No date and time listed

Accuracy of SCORTEN in predicting mortality in toxic epidermal necrolysis

BackgroundToxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material.MethodsA retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose.ResultsThe sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation.ConclusionOur data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

A Case Report of Three Guillain-Barré Syndrome During SARS-CoV-2 Pandemic: Promising Outcome in a Patient with History of Multiple Sclerosis

Neurologic complications in patients with coronavirus disease 19 (COVID-19) are common particularly in hospitalized patients. Guillain–Barré syndrome (GBS) is a rare complication of COVID-19. Most patients with GBS and COVID-19 presented with progressive, ascending limb weakness evolving over one to four days. There are some reported cases of GBS, mostly in form of case reports or case series, and also a comprehensive review on this topic. However, none of these cases experienced multiple sclerosis (MS) as an underlying disease. So, in this manuscript we reported three cases of COVID-19 induced GBS; one of them with history of MS and promising outcome after receiving five sessions of plasmapheresis and corticosteroid therapy.

DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE COMPLICATED BY SPONTANEOUS PNEUMOMEDIASTINUM IN A PATIENT AFTER ASYMPTOMATIC COVID-19 INFECTION

DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE COMPLICATED BY SPONTANEOUS PNEUMOMEDIASTINUM IN A PATIENT AFTER ASYMPTOMATIC COVID-19 INFECTION

P26 Challenging Scenario: Scleroderma/Sjogren overlap with dysautonomia

Introduction/BackgroundScleroderma Overlap conditions are well defined and often behave differently than their limited or diffuse counterparts. The treatment for such patients is usually tailored around the organ system involvement and severity. We present a challenging case of Scleroderma/Sjogren overlap with refractory Raynaud's phenomenon who posed treatment challenges due to severe autonomic dysfunction.Description/Method76-year-old Caucasian lady, non-smoker, who presented in 1990’s with dry eyes, dry mouth and severe Raynaud's phenomenon with recurrent digital ulceration which became infected on multiple occasions. ANA was 1:400 with Extractable nuclear antigen Ro and La positive. Anti DsDNA was negative and C4 was low. Antiphospholipid antibodies and cryoglobulins are negative. She failed calcium channels blockers and phosphodiesterase 5 inhibitors and was intolerant to intravenous (IV) Iloprost which was tried on multiple occasions. IV latanoprost was tried as well. This treatment was complicated when she developed postural hypotension and multiple fall episodes during vasodilator use. This was attributed to autonomic dysfunction secondary to her Sjogren syndrome. She was initiated on Injection Fludrocortisone, however her hypotensive episodes continued. She received monthly intravenous immunoglobulins 20gm (over two days) infusion for a few months for autonomic dysfunction with some response. She eventually developed recurrent diarrhoea and abdominal pain and bloating which was attributed to small bowel overgrowth with rapid bowel transit on a gastric emptying scan. She had a blocked bile duct as well which was unblocked using Endoscopic Retrograde Cholangiopancreatography. Over the next 8 years, she continued struggling with refractory Raynaud’s, having failed IV regional guanethidine blocks and digital sympathectomy. Her postural hypotension decompensated on multiple occasions necessitating plasmapheresis which provided some benefit. In 2020, she was detected to have a PET avid slowly progressing left upper lobe lung lesion. She underwent left video assisted thoracoscopy surgery with upper lobectomy. Histology was suggestive of adenocarcinoma. In 2021, she had another fall episode due to an acute/subacute infarct of left pons. She continues having postural hypotension and requires regular plasmapheresis sessions to manage her symptoms. She is also presently on Bosentan for her raynaud’s phenomenon.Discussion/ResultsThis is a case of overlap of Sjogren syndrome with scleroderma features. Management of Refractory Raynaud’s as part of her scleroderma phenotype was challenging. This case gave us the opportunity to explore all the treatment options available for Raynaud’s phenomenon albeit with poor outcome. She also struggled with autonomic dysfunction leading to postural hypotension and gastrointestinal symptoms which can be seen in upto 50% of patients with Sjogren syndrome. Autonomic failure is often thought to be immune mediated in Sjogren syndrome. This makes way for the use of intravenous immunoglobulin and plasmapheresis to treat these conditions as was done in this case. Increased risk of lung carcinoma with scleroderma is well documented. Autonomic dysfunction can also present as paraneoplastic syndrome with lung carcinoma, however it is more common with small cell lung carcinoma and our patient was diagnosed with Adenocarcinoma. We would have to wait and see if the resection of the tumour has any demonstrable effect on her dysautonomia.Key learning points/ConclusionOverlap connective tissue diseases are often difficult to manage in view of extensive disease heterogeneity. Clinicians need to be aware of challenges in managing Difficult Raynaud’s with Autonomic dysfunction. Treating physicians need to be aware of the high risk of lung malignancy and regular close monitoring is required. This case-based conference gives us the opportunity to discuss further management approaches for her.

P8.148: HLA Desensitization in Kidney Transplantation

Introduction: In the last decade, organ transplantation has been developing fast in Kazakhstan. 1892 transplants have been performed since 2012. Patients often need kidney (91.5%), heart (4.4%), liver (4%) transplantations. Nearly 100 kidney transplantations from living donors and 30 ones from deceased donors are performed annually. The most important factor hindering the long-term survival of recipients is HLA sensitization. The formation of specific antibodies to HLA may develop as a result of previous transplantation, blood transfusion or pregnancy. There are 3.5% highly sensitized patients among 3012 patients on the waiting list for kidney transplantation. This study aimed to review an effectiveness of desensitizing therapy during the preparation of patients for transplantation. Methods: This study included 13 patients with end-stage chronic kidney disease (CKD). The participants underwent a general clinical examination, a specialized immunological study to determine the level of antibodies to leukocyte antigens (anti-HLA) before and after the desensitization stages. Microsoft Excel was used to perform statistical analyses. Qualitative variables were summarized in the form of absolute frequency and percentages. Results: The proportion of male and female was 38.5% (5) and 61.5% (8), respectively. The average age of the participants was 44.8 years, ranging from 25 to 58 years. 30.8% (4) of patients had a decrease in the level of leukocyte antibodies after rituximab administration and three sessions of citrate plasmapheresis. In 23.1% (3) of patients, the level of sensitization remained same. An increase in the level of leukocyte antibodies was observed in 15.4% (2) of participants. 15.4% (2) of patients are currently at the second stage of desensitization. In 53.8% (7) of patients, a positive cross-match test is observed, which leads to the impossibility of kidney transplantation from living donor. A significant decrease in leukocyte antibodies was revealed in 53.8% (7) patients after repeated plasmapheresis sessions, despite the absence of differences in the level of antibodies after administration of rituximab and one plasmapheresis session. 46.2% (6) of the participants underwent only the first stage (rituximab) and one plasmapheresis session. 37.5% (3) of female had 5 or more pregnancies, which affects the increased immunological risk in CKD. 62.5% (5) of women had one pregnancy each and they had a decrease in the level of antibodies after rituximab and one plasmapheresis session. One patient has a significant decrease in the level of leukocyte antibodies after several sessions of plasmapheresis. 25% (2) undergo the first stage of desensitizing therapy. Conclusion: According to preliminary data, the combination of plasmapheresis and rituximab was insufficient to achieve a negative cross-match test and kidney transplantation. In this regard, we recommend adding the introduction of human immunoglobulin to desensitizing therapy. This study is ongoing.

316.8: Successful Desensitization and Transplantation of Kidney Transplant Recipients With Donor Specific Antibodies

Background: Kidney transplantation has indisputably changed the dynamics of renal medicine and restored hope among patients coming across fatal end-stage renal disease (ESRD). However, sensitization of human leukocyte antigen (HLA) hampers kidney transplantation. Our transplant center used a modified desensitization protocol. Methods: Desensitization protocol in our transplant center encompassed following mentioned strategy to achieve MFI values <1000 and negative CDC crossmatch for both T and B lymphocytes before proceeding for kidney transplantation: Two sessions of Plasmapheresis on day 1 and 2 → Injection Rituximab on day 2 after Plasmapheresis → No Plasmapheresis on day 3 → Eight sessions of Plasmapheresis after day 3 and IVIG 100mg/Kg/dose after each session of Plasmapheresis → Repeat HLA antibody detection test to confirm if DSAs are present against HLA with MFI values <1000 and CDC crossmatch is negative for both T and B lymphocytes; if NO then continue Plasmapheresis sessions with IVIG 100 mg/Kg/dose till MFI values are <1000 and CDC crossmatch is negative for both T and B lymphocytes or if YES then proceed for transplantation → Repeat dose of Rituximab post-transplantation. Results: All the six cases had moderate levels of DSAs against HLA except for one case with MFI value of 17962. With implementation of our modified desensitization protocol, we achieved low levels of DSAs with MFI value <1000 (Table 1). Patients were successfully transplanted with no adverse outcomes, such as kidney allograft rejection, on follow up (Table 2). Conclusion: In our transplant center, we successfully desensitized and transplanted six HLA sensitized kidney transplant candidates with moderate to high DSAs and T and B lymphocyte positive CDC crossmatch. Our desensitization protocol comprised of multiple plasmapheresis sessions with simultaneous low dose IVIG and Rituximab. Upon follow up, we did not witness any significant transplant related event such as allograft dysfunction or rejection. Keywords: Kidney Transplantation; Donor Specific Antibodies; Human Leukocyte Antigen; Desensitization Protocol.

Proprioceptive Stimuli as a New Type of Trigger for Epilepsy in Stiff Person Syndrome.

A healthy 74-year-old woman was diagnosed with Stiff-Person (SP) syndrome (encephalopathy and stiff leg) with amphiphysin autoantibodies and T1N1M0 breast cancer (HER2+, PR−, ER−). She received immunotherapy (2 high-dose steroid cycles and 7 plasmapheresis sessions), followed by right mastectomy, axillary chain lymphadenectomy, and adjuvant chemotherapy (letrozole, trastuzumab, and cyclophosphamide), with poor clinical response (Eastern Cooperative Oncology Group 4). After discharge, she presented to the emergency department with seizures induced by knee flexion of the stiff leg (Video 1). EEG showed epileptic seizures initiating in the left temporal lobe (Figure). Reduced presynaptic GABAergic inhibition could be the underlying mechanism of the core signs of amphiphysin-SP, which might explain the presence of epilepsy in these patients.1 However, no reflex proprioceptive seizures had been previously reported in SP.

Two PerPLEXing Cases of Hashimoto’s Encephalopathy Unresponsive to Steroid and Intravenous Immunoglobulin Therapy

Hashimoto’s encephalopathy is a nebulous entity over which much controversy exists. Often referred to as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), it describes a myriad of neurological sequelae that typically are observed to occur in patients with the presence of thyroid antibodies. We aim to raise clinical awareness of this seldom diagnosed entity as a potential etiology for altered mental status in patients who present with supporting clinical features and elevated thyroid antibodies. While steroid responsiveness is deemed a typical presenting feature of this medical condition, our cases aim to describe two cases that required escalation of therapy to intravenous immunoglobulins, and ultimately, plasmapheresis therapy for improvement in their clinical status. Our patients had a dramatic improvement in their mentation within three to four sessions of plasmapheresis, improving rapidly toward their baseline. Such a dramatic improvement, coupled with the corresponding reduction in their thyroid antibody titer supports the diagnosis of Hashimoto's encephalopathy and highlights the importance of having a low clinical threshold for the diagnosis of this entity in patients who, despite extensive evaluation, reveal no apparent cause for their altered mental status.

Les techniques de plasmaphérèse thérapeutique : une alternative à la rupture d’approvisionnement en immunoglobuline polyvalente dans les pathologies auto-immunes. Étude médico-économique

IntroductionThe supply of human polyvalent immunoglobulin has been under severe pressure for several years. This has led to a prioritisation of indications and a record increase in the amount of reimbursement without solving the problem of demand. Treatment by therapeutic plasmapheresis appears to be an alternative to be considered for the treatment of certain dysimmune diseseases. To discuss this alternative, we are conducting a medico-economic study comparing the polyvalent immunoglobulin strategy versus different therapeutic plasmapheresis system in the treatment of a chronic dysimmune disease. Population and methodThe medico-economic study was conducted using the example of a 75 kg patient with chronic polyradiculoneuritis dependent on chronic therapy with a comparison of sequential treatment with one session of therapeutic plasmapheresis versus a course of intravenous polyvalent immunoglobulin. The medico-economic study includes an evaluation from a public health care system perspective complemented by a hospital-based approach that justifies estimating the cost of different therapeutic plasmapheresis systems based on a bottom-up micro-costing approach. ResultsFrom the point of view of the care system, for information, a 20 g bottle of polyvalent immunoglobulin has a similar cost to a therapeutic plasmapheresis session. In our example, the cost of a maintenance treatment repeated every 2 to 4 weeks in chronic polyradiculoneuritis in a 75 kg patient is 1284.13 euros for a therapeutic plasmapheresis session versus 7331.60 to 9426.84 euros for a 1.5 to 2 mg/kg polyvalent immunoglobulin treatment. Furthermore, from the point of view of the hospital system, the cost of the different TT techniques evaluated varies moderately with the cost depending mainly on the quantity of albumin infused or the medical device used. ConclusionIn the chronic sequential treatment of chronic polyradiculoneuritis, the cost of therapeutic plasmapheresis could be lower than with polyvalent immunoglobulin from a healthcare system perspective. The cost to the health care facility between different therapeutic plasmapheresis techniques differs little. This study provides arguments suggesting that if therapeutic plasmapheresis can be implemented with a dedicated technical platform, it is a serious alternative to be considered without additional costs.

Efficacy of intravenous combined immunosuppression with plasmapheresis in adult patients with refractory primary focal segmental glomerulosclerosis

Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS. Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed. Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P= 0.018 and P= 0.018, respectively). eGFR levels did not change statistically (P= 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient. Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.

In vitro fertilization and hypertriglyceridemic pancreatitis: Case report

Few cases of hypertriglyceridemic pancreatitis have been reported in women during a vitro fertilization treatment (IVF) cycle. Here, we describe a 41-year-old woman with primary infertility and a history of acute pancreatitis (of unknown etiology) who was started on high dose ethinyl estradiol to prepare for transfer of cryopreserved embryos. She subsequently presented with nausea, vomiting, and abdominal pain to an emergency room and was found to have hypertriglyceridemic pancreatitis. Her hospitalization involved a prolonged intensive care unit stay in which she underwent three sessions of plasmapheresis. Eventually, with discontinuation of ethinyl estrogen, aggressive intravenous fluid hydration, plasmapheresis, a low-fat diet, and gemfibrozil, she had resolution of severe hypertriglyceridemia and all symptoms related to acute pancreatitis. Our case highlights the possibility that ethinyl estradiol, a commonly used form of estrogen for endometrial preparation during IVF cycles, may cause severe hypertriglyceridemia and acute pancreatitis in certain predisposed individuals. Only seven cases of hypertriglyceridemic pancreatitis during in vitro fertilization have been previously reported, and only one of these prior cases experienced pancreatitis during transfer of cryopreserved embryos like our patient. Our case, along with the few prior reported cases, demonstrate hypertriglyceridemic pancreatitis can occur during IVF. Further work is needed to understand the effects of exogenous estrogen on lipids for women undergoing IVF.

Overcoming high pre-transplant isoagglutinin titers using high-dose intravenous immunoglobulin, salvage plasmapheresis, and booster rituximab without splenectomy in ABO-incompatible living donor liver transplantation: a case report

High pre-transplant isoagglutinin is a risk factor for antibody-mediated rejection in ABO-incompatible living donor liver transplantation. A 55-year-old man with alcoholic liver cirrhosis underwent ABO-incompatible living donor liver transplantation. The initial isoagglutinin immunoglobulin G titer was 1:1,024. Despite five sessions of plasmapheresis, the isoagglutinin titer was not significantly reduced (from 1:1,024 to 1:512). We decided to perform 11 plasmaphereses and proceed with liver transplantation regardless of the isoagglutinin titer (1:128 at transplantation day). Instead, we planned to administer 0.5 g/kg intravenous immunoglobulin and booster rituximab (200 mg) after transplant. On postoperative day 6, the isoagglutinin titer increased from 1:32 to 1:64, and the patient received plasmapheresis twice. The patient maintained stable liver function without evidence of further complications or rejection. The high-dose intravenous immunoglobulin, salvage plasmapheresis, and booster rituximab protocol might be able to overcome a pre-transplant high isoagglutinin titer in ABO-incompatible living donor liver transplantation without splenectomy.

Therapeutic Plasmapheresis: Seven Year Experience of an Intensive Care Unit in Portugal.

Therapeutic plasmapheresis is a therapeutic procedure in which the patient's blood is passed through a medical device which separates out plasma from other components of blood. The plasma is removed and replaced with a replacement solution. Studies on the use of plasmapheresis in critically ill patients are scarce. The aim of this study was to review all therapeutic plasmapheresis sessions carried out in the Hospital Beatriz Ângelo intensive care unit. An observational retrospective study was conducted between April 2012 and March 2019. All patients who underwent therapeutic plasmapheresis in the intensive care unit were included, and plasmapheresis sessions held outside the intensive care unit were excluded. Of 46 patients, 63% were men (n = 29), with a median age of 53 years. The most frequent diagnoses were hypertriglyceridemia-induced pancreatitis, vasculitis, autoimmune haemolytic anaemia, and atypical haemolytic-uremic syndrome. A total of 198 plasmapheresis sessions were carried out in the intensive care unit. Most of the used replacement solutions were fresh frozen plasma (34.4%), albumin/crystalloid (24.2%), and albumin/fresh frozen plasma (19.2%). The most common complications were hydroelectrolytic changes (84; 42.4%) and coagulation disorders/thrombocytopenia (65; 32.8%). There was no need to interrupt any plasmapheresissession due to complications related to the patient. Therapeutic plasmapheresis is an urgent procedure that can reduce morbidity and mortality in critically ill patients. This justifies that 37% of patients started the technique before the diagnostic confirmation. The indications for plasmapheresis and the choice of replacement solution were in agreement with the guidelines. Despite the risk of bleeding, no haemorrhagic complications were recorded. Therapeutic plasmapheresis is a complex technique that requires specific training. The indications are diverse, and some are not consensual. Complications were frequent, but they did not increase morbidity.