Comparison of efficacy of plasma exchange versus intravenous immunoglobulin as an add-on therapy in acute attacks of neuromyelitis optica spectrum disorder.

INTRODUCTION: Plasma exchange (PE) is considered a Category II option for the treatment of acute attacks and relapse cases of neuromyelitis optica spectrum disorder (NMOSD). However, neurologists are also considering intravenous immunoglobulins (IVIg) as an add-on therapy for this disorder. AIMS: The aim of this study is to evaluate the efficacy of PE in acute attacks of NMOSD when compared with IVIg, in terms of improvement in the Expanded disability status scale (EDSS) and activities of daily living (ADL) scale score and levels of anti-Aquaporin P4 (AQP4) antibody in seropositive patients. METHODS: We enrolled 43 NMOSD patients in two groups: Group 1 (n = 29) received steroids and PE, and Group 2 (n = 14) received steroids with IVIg. The baseline EDSS and ADL scores were recorded and compared with scores at the end of therapy, 4 weeks, and 3 months after. Also, anti-AQP4 antibody was measured at baseline and post-therapy in seropositive patients of both groups. RESULTS: We observed a significant difference in EDSS (p = 0.00) and ADL score (p = 0.00) at day 10 and 3 months in both groups. However, no significant difference in EDSS, as well as ADL score from baseline (p = 0.83; p = 0.25) to 3 months (p = 0.85; p = 0.19), was observed when delta change of score at 3 months was compared across the two groups (p = 0.39; p = 0.52). We observed improved visual acuity in both groups with mild improvement in findings of magnetic resonance imaging at 3 months. We observed a significant decline in AQP4 antibody concentration (at day 10) in group 1 seropositive patients (p = 0.013) with improved EDSS (p = 0.027) and ADL scores (p = 0.026) of these patients. CONCLUSIONS: PE should be considered as a choice of an add-on therapy in anti-AQP4 antibody-positive NMOSD patients compared with IVIg as it is more effective in reducing antibody concentrations.

Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.

BACKGROUND: Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established. AIM: To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation. METHODS: Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed. RESULTS: A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P < .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures. CONCLUSION: TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Use of convalescent plasma for COVID-19 in India: A review & practical guidelines.

Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.

Therapeutic Plasma Exchange: A Lifesaving Therapy in Case of ANCA-associated Vasculitis with Diffuse Alveolar Hemorrhage.

How to cite this article: Tripathi PP, Sharma RR, Chhabria B, Hans R, Sehgal IS. Therapeutic Plasma Exchange: A Lifesaving Therapy in Case of ANCA-associated Vasculitis with Diffuse Alveolar Hemorrhage. Indian J Crit Care Med 2021;25(7):828-829.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

Comparison of efficacy of low and high dose prophylactic platelet transfusion therapy in thrombocytopenic haemato-oncology patients.

INTRODUCTION: To determine an optimal platelet dose in thrombocytopenic patients is important for their judicious use. Transfusing platelets in different doses and comparing their post transfusion response can achieve this. AIM: To compare the efficacy of low and high dose single donor apheresis platelets (SDAP) with standard dose transfusions in terms of Corrected Count Increment (CCI), Percent Platelet Recovery (PPR) and transfusion free interval. METHOD: It was a prospective case control study done from January 2016 to April 2017. Twenty-eight hemato-oncology patients with CCI ≥5000 at 20-24 hours after standard dose (3 × 1011/unit), received low dose (1.5 × 1011 platelets/unit) and high dose (>4 × 1011 platelets/unit) SDAP. CCI and PPR were calculated after 20 to 24 hours of transfusion. Transfusion free interval and bleeding episodes were also noted. Grading was done according to WHO bleeding scale. RESULT: There was no statistical difference in CCI and PPR when standard dose was compared with low dose (CCI: p = 0.92, PPR: p = 0.89). When standard and high dose was compared, standard dose gave better results than the high dose in terms of CCI (p = 0.006) and PPR (p = 0.008) although the post transfusion increments were comparable (p = 0.938). High dose gave better (p = 0.005) platelet count increments than low dose but CCI (p = 0.04) and PPR (p = 0.05) was significantly less than the low dose. The difference in transfusion free intervals after three doses was not significant. Donor exposure to the patients was significantly (p = 0.000) reduced to 17.5%. CONCLUSION: Possibility of low dose as an alternative to standard dose can be considered in view of comparable platelet response indicators and significantly reduced donor exposure.

Efficacy of therapeutic plasma exchange in a patient with coagulation inhibitors (acquired haemophilia A) - A case report.

Acquired haemophilia A (AHA) is a rare disorder with mostly idiopathic aetiology that leads to factor VIII (FVIII) deficiency due to coagulation inhibitors formation. Treatment protocol includes immunosuppression and Factor VIII bypassing agents including activated Prothrombin Complex Concentrates (PCC). Nevertheless, the role of plasma exchange is not clear in the treatment of AHA. We report a case of 73 year old male who presented with haematuria, prolonged activated partial thromboplastin time (APTT) and a very high titres of Factor VIII inhibitors of 98 Bethesda units (BU) and was diagnosed with acquired haemophilia A. He failed to respond to multiple immunosuppressive therapies including rituximab. Therefore, therapeutic plasma exchange (TPE) therapy was planned due to persistence of haematuria despite immunosuppressive therapies. After five cycles of plasma exchange, APTT became normal, haematuria subsided and Factor VIII inhibitors became negative. Patient was discharged without any bleeding and in a stable condition. In this index case, plasma exchange played a very crucial role, resulting in recovery of the patient. These results advocate that therapeutic plasma exchange is an effective therapy for acquired haemophilia A.

Therapeutic whole blood exchange in the management of methaemoglobinemia: Case series and systematic review of literature.

BACKGROUND: Therapeutic whole blood exchange (TWBE) has been used as an alternative when methylene blue (MB) fails in severe methaemoglobinemia. However, there are limited data on the efficacy and safety of TWBE. OBJECTIVES: Our aim was to report our institutional experience with TWBE. We also perform a systematic review of published literature. METHODS: We retrospectively reviewed our respiratory intensive care unit database to identify cases of methaemoglobinemia managed with TWBE. A systematic review of the PubMed database was performed to identify similar cases (≥12 years). We report the indications, utility, and safety of therapeutic exchange in methaemoglobinemia. The procedural details were also noted. RESULTS: We identified five subjects who received TWBE for methaemoglobinemia (median methaemoglobin level 39%; range 19.6-42.4%). TWBE was successful in all five cases and no adverse events were encountered. Our review identified 27 additional subjects. The median methaemoglobin level was 37.5% (range 3.7-81%). The most common indication (n = 24, 75%) for therapeutic exchange was a lack of response to MB. A majority of the subjects (n = 26/32, 81.2%) survived. No procedure-related complications were reported. CONCLUSION: TWBE is a safe and effective salvage modality for adults with methaemoglobinemia, when MB is either contraindicated or ineffective. Future studies should standardise therapeutic exchange in the management of methaemoglobinemia.

Role of Plasma Exchange in a Steroid- and IVIG-Refractory Patient with Acute Disseminated Encephalomyelitis: A Case Report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease usually affecting children and is treated with high-dose steroid therapy. CASE REPORT: An 8-year boy presented with limbs weakness and complete loss of vision and was resistant to steroid therapy. He was further treated with plasma exchange and showed full recovery from the neurological deficit. CONCLUSION: Therapeutic plasma exchange appears to be effective in ADEM patients in reversing the neuropathological process especially refractory to steroids and intravenous immunoglobulin.

Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion.

BACKGROUND: Platelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated. AIMS: To determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion. MATERIALS AND METHOD: 149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1 h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test. RESULT: Patients showed statistically significant recovery in terms of PPI, CCI and PPR at 1 h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173 ±â€¯2692) than for incompatible (5888 ±â€¯1526) and for uncross-matched (8140 ±â€¯1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p < 0.0001). CONCLUSION: Platelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.

Initial trends of individual donation nucleic acid testing in voluntary & replacement donors from a tertiary care centre in north India.

Background & objectives: Individual donation nucleic acid testing (ID-NAT) is considered as sensitive technology to assess blood safety from viral transfusion-transmissible infections (TTIs) in blood donors. The present study was aimed to analyze the results of ID-NAT for three years (2013-2015) with special reference to different types of donors and their age ranges in a tertiary care centre in north India. Methods: The results of ID-NAT for three years were retrospectively analyzed at our centre. A total of 168,433 donations were tested with ID-NAT, of which 10,467 were tested with Procleix® Ultrio® reagents and 157,966 were tested with Procleix®UltrioPlus® reagents, and the results were compared with those of serology to calculate the NAT yield in voluntary, replacement, first-time and repeat donors. Results: A combined NAT yield was observed as one in 1031 out of 167,069 seronegative donations with HBV yield as one in 1465, HCV yield as one in 3885 and HIV-1 as one in 167,069. Yield for co-infection (HCV and HBV) was one in 41,767. A high NAT yield was observed in replacement donors (1 in 498) as compared to voluntary donors (1 in 1320). Interpretation & conclusions: Addition of NAT to serology improved the blood safety in our centre interdicting possibility of 150 TTIs annually. It has also reemphasized the safety of voluntary over replacement donors. The results also highlight the need of proper counselling, notification and referral guidelines of NAT yield donors in our country and other countries which lack them.

Cost-minimization analysis in the Indian subcontinent for treating Guillain Barre Syndrome patients with therapeutic plasma exchange as compared to intravenous immunoglobulin.

BACKGROUND: Therapeutic Plasma Exchange (TPE) and Intravenous Immunoglobulin both are first-line treatments for Guillain Barre Syndrome; however, there is a significant difference in cost. We undertook this study to assess the cost minimization for treating Guillain Barre Syndrome patients. METHODS: A prospective randomized controlled trial was undertaken, in which 40 Guillain Barre Syndrome (GBS) patients with a GBS disability score of grade four and five were enrolled. A societal perspective was adopted for the analysis and assessment of both the health system cost and out-of-pocket expenditures. Cost-minimization analysis was undertaken as both the treatments were equally effective at the end of 12 weeks. RESULTS: No statistically significant differences were observed in the GBS Disability scores during overall treatment course in both treatment groups. The Out-of-pocket cost for the immunoglobulin (IVIG) group was INR 219 247 (4298 USD) and for the TPE group was INR 104 070 (2040.5 USD). Overall INR 86 685 ($1700), that is, 53% higher cost was observed in IVIG group without any concomitant health outcome benefit. CONCLUSION: In comparison with IVIG, TPE appears to be the better option for treatment of GBS in cost-constraint countries like ours to provide an economic treatment option to most average people.

Efficacy and safety of therapeutic plasma exchange by using apheresis devices in pediatric atypical hemolytic uremic syndrome patients.

BACKGROUND: Therapeutic plasma exchange (TPE) in atypical hemolytic uremic syndrome (aHUS) is considered as first line treatment as per current American Society for Apheresis (ASFA) guidelines. But there is very limited data available in the literature regarding efficacy and safety of TPE procedures in pediatric aHUS patients. AIM: To assess the safety and efficacy of TPE by using apheresis devices in pediatric aHUS patients. MATERIALS AND METHODS: We did a retrospective analysis of all TPE procedures performed in aHUS pediatric patients over a period of 13 years (2001-2013). TPE procedures were done on two different devices daily or on alternate days depending on clinical condition of the patient. Adverse events if any were noted and analyzed. Pre and post procedural laboratory profiles were analyzed to assess the response to TPE therapy and patients were categorized accordingly. RESULTS: A total of 169 TPE procedures (range of 1-22/patient with an average of 7.6 procedures/patient) were performed on 30 pediatric patients. Twenty four patients had more than 3 TPE procedures. Sixteen patients were complete responders, 5 were partial responders and 3 were non responders. The time between onset of illness and start of TPE therapy was 1-4 days in complete responders, 5-7 days in partial responders and 8-9 days in non- responders. Adverse events were observed in 13 (7.7%) procedures. CONCLUSION: TPE is a safe and effective therapeutic modality in pediatric aHUS if instituted early in the course of disease with a minimum of four to five procedures. J. Clin. Apheresis 31:381-387, 2016. © 2015 Wiley Periodicals, Inc.

Donor lymphocyte infusions: An experience from a tertiary care center of North India.

Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft - versus - leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%-20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient's developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies.

Combination of rituximab with therapeutic plasma exchange in a refractory case of thrombotic thrombocytopenic purpura (TTP).

Therapeutic plasma exchange is established treatment for patients with thrombotic thrombocytopenic purpura (TTP) and for refractory cases immunosuppressive therapy can also be considered. We present a refractory case of TTP which was managed with therapeutic plasma exchange and rituximab.

Dramatic response to plasma exchange in systemic lupus erythematosus with acute complications: Report of two cases.

Acute exacerbations and complications are common in patients of systemic lupus erythematosus (SLE) despite of adequate long-term therapy with immunosuppressive drugs. So other options like therapeutic plasma exchange (TPE) can be considered as part of management. Here, we share our experience of two patients of SLE with acute complications who were successfully managed with TPE.