Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Large volume plasmapheresis using a single-use immunoadsorption column: A cost-effective approach for desensitization in ABO-incompatible liver transplant.

INTRODUCTION: Liver transplant is a life-saving treatment, but due to the limited availability of suitable liver donors, ABO-incompatible liver transplants (ABOi-LT) are conducted to increase the availability of liver donors. Perioperative desensitization for ABOi-LT is an established strategy to circumvent the risk of graft rejection. A single prolonged session can be performed to achieve the desired titers to avoid using multiple immunoadsorption (IA) columns or off-label reuse of single-use columns. This study retrospectively assessed the effectiveness of a single prolonged plasmapheresis session using IA as a desensitization strategy in live donor liver transplant (LDLT). MATERIALS AND METHODS: This retrospective observational study conducted at a center for liver diseases in North India on six ABOi-LDLT patients who underwent single prolonged IA sessions in the perioperative period from January 2018 to June 2021. RESULTS: Median baseline titer in patients was 320 (64, 1024). The median plasma volume adsorbed was 7.5 volumes (4, 8) per procedure, with a mean procedure time of 600 min (310-753). The reduction in titer ranged from 4 log to 7 log reduction per procedure. Two patients developed transient hypotension during the procedure, which was managed successfully. The median duration of pre-transplant hospital stay was 1.5 days (1, 3). CONCLUSION: Desensitization therapy helps overcome the ABO barrier and decreases the waiting period before a transplant when ABO identical donors are unavailable. A single prolonged IA session reduces the cost of additional IA columns and hospital stay, thus making it a cost-effective approach to desensitization.

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

Survey based cross-sectional study to analyse the variation of practices at blood centres during COVID-19 pandemic in India.

India has almost 3,000 blood centres collecting more than 11 million units annually. Maintaining blood supply during the COVID-19 pandemic is a huge challenge. We conducted a cross-sectional study by an online survey to analyse the variation of practices across blood centers of India during this pandemic. A total of 196 blood centers completely responded to the online survey. Most of the blood centres who responded were part of Government hospitals (60 %), part of an academic institutes (55.6 %) and were directly supporting a COVID hospital (67.5 %). Almost 95.4 % blood centers reported reduction of blood donation mainly due to lockdown (50 %) and inability to conduct camps (17.3 %). Scheduling blood donations was one of the most difficult to implement strategy for maintaining adequate blood donation (40.2 %). Blood center manpower management was also a challenge and upto 48 % blood centers operated in two batches to ensure social distancing in blood banks and reduce the risk of exposure. Hemato-oncology (36.8 %) and obstetrics (33.7 %) were major utilizer of blood during the pandemic. There were marked variations in use of PPE by blood banks staff as well as strategies adopted while conducting immunohematology tests on COVID-19 positive patients samples. This pandemic has highlighted some of the major limitations of the health services but blood services have risen to the challenge and strived to maintain the blood supply chain while ensuring blood donor and staff safety. The wide variations in the practices adopted highlights the need for uniform guidelines for blood services in future pandemics.

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.

Autoanti-C in a patient with primary sclerosing cholangitis and autoimmune hemolytic anemia: a rare presentation.

Primary sclerosing cholangitis (PSC) is rarely associated with autoimmune hemolytic anemia (AIHA), and the presence of specific autoantibodies has not been reported previously. We present a unique case report of PSC associated with AIHA implicating autoanti-C. A 17-year-old girl was admitted to our hospital with PSC along with AIHA. Her blood sample demonstrated a positive direct antiglobulin test and a positive autocontrol in the antihuman globulin phase, confirming the patient had warm-reactive AIHA. Further testing showed the possibility of anti-C. The patient's Rh phenotype was C+D+E­c­e+. Further testing with select cells, serial alloadsorption, and an elution confirmed anti-C specificity. The patient was transfused with two C­, crossmatch-compatible packed red blood cell units. The patient's hemoglobin level and general condition showed improvement. This unique case report shows PSC associated with AIHA caused by autoanti-C. Usually, warm AIHA presents with a panreactive pattern, and it is difficult to find compatible blood. In this rare case, we could determine the specific antibody; efforts should always be made in cases of AIHA to identify the specificity of autoantibody.

An Exploratory Study of the Differences in Attitudes and Motives Regarding COVID-19 Plasma Donation.

Background: Understanding the attitude and motives and differences between voluntary and replacement blood donation is the key to the sustainable availability of this precious resource. This study aimed to assess the attitude and motives for convalescent plasma (CP) donation in the recovered COVID-19 plasma donors and further understand the differences between voluntary and replacement donation. Materials and Methods: This prospective cross-sectional survey-based study was conducted among500 COVID-19 recovered blood donors who visited for CP donation at a tertiary care super-speciality centre in northern India. Data were collected using a structured questionnaire based on donor attitude, motives, and belief, which was validated by the experts of Psychiatry, Transfusion Medicine, and Epidemiology and was administered by the online medium. Results: The study's findings depicted that voluntary plasma donors were previously regular blood donors (36.8%) compared to replacement plasma donors (26.4%). Almost all voluntary donors (99.5%) showed altruistic reasons to donate plasma and expressed that donating plasma is a good way to save a life, and it was more than for replacement plasma donors (p=0.004). The motives of most voluntary plasma donors were to contribute to society, and they believed that donating plasma is a good way, while it was not the case for most replacement plasma donors (p=0.02). Voluntary donors were more eagerly willing to donate plasma to help COVID sufferers (40.9%) when compared to replacement donors (33.2%) (p=0.037). Conclusion: Most voluntary plasma donors were regular whole blood donors and were keen to contribute to society. Convalescent plasma donation during this time of grief and loss was considered a moral responsibility by voluntary donors. The impact of media was more highly perceived in voluntary plasma donors when compared to replacement donors.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04425915.

Impact of alternative strategies to improve the pool of blood donation by off-hour donation: A pilot study and its future prospects.

BACKGROUND: The escalating need for blood component due to increasing accidents and surgeries are always challenging for blood banks and hospitals. In this fast and busy world, collecting blood from a healthy and voluntary donor is quite challenging due to time constraints. Many blood donors who wish to donate blood were unable to go to the blood bank because of simultaneous operational timings of the blood bank and office hours of the donors. We dealt with this concern by extending the donation hours and also started collecting blood on the weekends following LAARC (Listen, Acknowledge, Assess, Respond, Confirm) methodology as a pilot project for improving blood donor convenience and satisfaction at the blood bank. METHODOLOGY: It was a prospective observational pilot study conducted at the government tertiary care institute in the Department of Transfusion Medicine from December 2018 to June 2019. All blood donations were made as per the guidelines laid down by the Drug and Cosmetic Act. The donation timings were divided as office-hour donations (8 am to 5 pm on weekdays) and off-hours donations (5 pm to 8 pm, weekends and holidays). RESULTS: In this pilot project, over 7 months out of a total of 1,591 donations, 664 donations (41.73%) were done during the off-hours. The donor experiences were pleasing, and they felt extra cared due to the convenient donation timings. CONCLUSIONS: Increasing the donation base needs more donor-friendly timings for the pleasant donation experience without hampering their work. More extensive studies should be conducted to include such strategies for increasing voluntary blood donation.

Sustained expression of inflammatory monocytes and activated T cells in COVID-19 patients and recovered convalescent plasma donors.

INTRODUCTION: Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID-19) patients and recovered patients. METHODS: Moderate COVID-19 patients (n = 34) at Lok Nayak Hospital, New Delhi, and COVID-19 recovered patients (n = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals (n = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry. RESULTS: A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1-α, monocyte chemotactic protein-1, macrophage migration inhibitory factor, vascular endothelial growth factor-A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)-6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon-γ response, and increased level of acute-phase protein SAA1 in the serum of COVID-19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL-18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8+ T cells, A proliferation-inducing ligand, and B-cell activating factor receptor+ B cells compared with healthy subjects. CONCLUSIONS: Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells.

Effects of therapeutic plasma exchange on liver function test and coagulation parameters in acute liver failure patients.

BACKGROUND: Currently the treatment of choice for critical liver failure is liver transplantation. Liver failure is treated conservatively until a matching liver donor becomes available. The therapeutic plasma exchange (TPE) plays an important role as a bridge to transplantation by removing accumulated toxins from patient plasma, as well as restoring the coagulation profile. METHOD: This was a retrospective study on critically ill liver disease patients who underwent TPE from January 2012 to September 2015. The data were collected for the analyses of coagulation parameters, liver function tests, renal function tests, model for end-stage liver disease (MELD) scores, mortality, and hospital stay. RESULTS: In the study duration, a total of 45 patients with critical liver disease underwent therapeutic plasma exchange. The TPE resulted in a statistically significant reduction in the bilirubin level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time (PT), international normalized ratio (INR), serum ferritin level and MELD scores. Higher MELD scores in both pre- and post-TPE were associated with higher mortality during the hospital stay. CONCLUSION: The TPE is safe and well-tolerated, and it improves coagulation profile and liver function tests in critically ill liver disease patients, but the overall survival remains low.

Effects of therapeutic plasma exchange on liver function test and coagulation parameters in acute liver failure patients

ABSTRACT Background: Currently the treatment of choice for critical liver failure is liver transplantation. Liver failure is treated conservatively until a matching liver donor becomes available. The therapeutic plasma exchange (TPE) plays an important role as a bridge to transplantation by removing accumulated toxins from patient plasma, as well as restoring the coagulation profile. Method: This was a retrospective study on critically ill liver disease patients who underwent TPE from January 2012 to September 2015. The data were collected for the analyses of coagulation parameters, liver function tests, renal function tests, model for end-stage liver disease (MELD) scores, mortality, and hospital stay. Results: In the study duration, a total of 45 patients with critical liver disease underwent therapeutic plasma exchange. The TPE resulted in a statistically significant reduction in the bilirubin level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time (PT), international normalized ratio (INR), serum ferritin level and MELD scores. Higher MELD scores in both pre- and post-TPE were associated with higher mortality during the hospital stay. Conclusion: The TPE is safe and well-tolerated, and it improves coagulation profile and liver function tests in critically ill liver disease patients, but the overall survival remains low.

Approach of pharmacists and herbalists while offering guidance on potentially malignant oral lesions: a cross-sectional survey.

OBJECTIVES: To investigate the approach of both pharmacies and herbalists' shops while offering a proper advice for patients seeking guidance on a potentially malignant oral lesion. MATERIALS AND METHODS: A cross-sectional, descriptive study was undertaken using the standardized patient approach on a representative sample of pharmacies and herbalists' shops in Bhopal city. The study sample was selected by stratified random sampling technique and was contacted by telephone. Our patient's introductory statement was, "I have a painful ulceration on the tongue since 3 months. What would you advise?" To avoid the hypothetical bias in telephone answers, another study was designed for two regions of the city, of which pharmacies were visited in one and herbal shops in the other one. RESULTS: A total of 497 establishments were contacted. Out of these, 368 were pharmacies (74.1%) and 129 were herbalists' shops (25.9%). Patients with potentially malignant lesions were more frequently referred to a dentist (16.03%) or a physician (23.36%) by the pharmacies compared to the herbalists' shops. In contrast, most of the herbalists' shops prescribed over-the counter (OTC) remedies (66.66%) and showed no interest in referring the patient to a dentist or a physician. CONCLUSION: Apart from pharmacists, the new probable off-clinical counselors (herbalists and pharmacy assistants) have been identified as potential factors of patient diagnostic delay in oral cancer. Educational strategies to improve advice and referral for these identified groups should be designed.