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The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immunodeficiencies has raised concerns about the ability of immunoglobulin preparations to neutralize VDRVs. We investigated the capacity of immunoglobulin to neutralize rubella vaccine virus and 4 VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by immunoglobulin preparations, but the VDRV isolates from patients after intrahost evolution, 2–6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while immunoglobulin replacement therapy can be expected to provide protection from rubella virus infection. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors cause rare but potentially fatal neuromuscular complications, leading to a concern to use these agents in cancer patients with pre-existing autoimmune or inflammatory neuromuscular diseases. We report two such patients with paraneoplastic dermatomyositis and "seronegative" paraneoplastic demyelinating neuropathy, respectively, who have been successfully treated with immune checkpoint inhibitor monotherapy as well as maintenance intravenous immunoglobulin. While controlling the paraneoplastic or autoimmune neuromuscular diseases, the use of intravenous immunoglobulin did not compromise the anti-cancer effect of immune checkpoint inhibitor.

Patients with severe primary immunodeficiency are at risk for complications from live-attenuated vaccines. Here, we report a case of a vaccine-associated paralytic polio and Bacille Calmette-Guérin disease in a 6-month-old girl with severe combined immunodeficiency resulting from homozygous recombinant activating gene 1 deficiency. The patient was successfully treated with intravenous immunoglobulins and oral pocapavir for poliovirus, and antimycobacterial therapy for regional Bacille Calmette-Guérin disease, allowing stem cell transplant. Following transplantation, poliovirus type 3 with 13 mutations was detected from cerebrospinal fluid but not from stool, indicating ongoing viral evolution in the central nervous system despite pocapavir treatment. Clinical improvement and immune reconstitution allowed the patient to be successfully discharged with no further detection of poliovirus. [ABSTRACT FROM AUTHOR]

Copyright of Salud Uninorte is the property of Fundacion Universidad del Norte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The presence of residual activated coagulation factor XI (FXIa) in some commercial intravenous immunoglobulin (IVIG) products has been identified as the root cause of a small number of thromboembolic events in patients who had received such therapy. Our objectives here were to design and evaluate the manufacturing process of GC5107, a 10% glycine-stabilized IVIG product, for its capacity to remove FXIa. The manufacturing process included a cation exchange chromatography (CEX) step, which employs a resin that binds immunoglobulin G (IgG) with high capacity. Procoagulant activity was assessed using Western blot analysis, enzyme-linked immunosorbent assay, thrombin generation assay, chromogenic FXIa assay, and non-activated partial thromboplastin time (NaPTT) assay. A spiking study in which large quantities of FXIa were added to samples before CEX chromatography was used to examine the robustness of the process to remove FXIa. Western blot and ELISA analyses demonstrated that residual FXIa remained in the intermediate manufacturing products until after CEX chromatography, when it was reduced to undetectable levels. The spiking study demonstrated that CEX chromatography removed >99% of FXI protein and reduced FXI activity to below detection limits, even in samples containing 158-fold greater FXIa levels than that of normal samples. Procoagulant activity in 9 consecutive lots of GC5107 was reduced to below the detection limits of the thrombin generation and chromogenic FXIa assays (250 s in all 9 lots indicated very low levels of procoagulant activity. We demonstrate that a novel 10% IVIG manufacturing process including CEX chromatography is a robust means of removing FXIa from the final preparation.

Background: Intravenous immune globulin (IVIg) is frequently used in some neurological diseases and is also the first-line therapy in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. We aimed to evaluate the frequency and characteristics of headaches, which is one of the most common side effects of IVIg treatment. Methods: Patients who received IVIg treatment for neurological diseases were prospectively enrolled in 23 centers. Firstly, the characteristics of patients with and without IVIg-induced headaches were analyzed statistically. Then, patients with IVIg-induced headaches were classified into three subgroups determined by their history: no primary headache, tension-type headache (TTH), and migraine. Results: A total of 464 patients (214 women) and 1548 IVIg infusions were enrolled between January and August 2022. The frequency of IVIg-related headaches was 27.37% (127/464). A binary logistic regression analysis performed with significant clinical features disclosed that female sex and fatigue as a side effect were statistically more common in the IVIg-induced headache group. IVIg-related headache duration was long and affected daily living activities more in patients with migraine compared to no primary headache and TTH groups (p = 0.01, respectively). Conclusion: Headache is more likely to occur in female patients receiving IVIg and those who develop fatigue as a side effect during the infusion. Clinicians' awareness of IVIg-related headache characteristics, especially in patients with migraine, may increase treatment compliance. [ABSTRACT FROM AUTHOR]

AbstractPrimary immunodeficiency (PI) patients may still experience persistent viral and bacterial respiratory infections with ongoing treatments. We report a challenging case of a PI patient who experienced recurrent viral respiratory infections despite receiving standard immunoglobulin replacement therapy. The patient was subsequently managed with immune globulin intravenous, human-slra (ASCENIV™) that contains elevated antibodies against multiple respiratory pathogens. The patient demonstrated significant clinical improvement with a resolution of persistent and debilitating viral respiratory infections and associated sequela.

In late 2019, SARS-CoV-2 was detected in China and spread worldwide. In rare cases, children who were infected with COVID-19 may develop multisystem inflammatory syndrome (MIS-C), which could have higher mortality than COVID-19 itself. Therefore, diagnosis and management are critical for treatment. Specifically, most of the initial treatment options of MIS-C choose intravenous immunoglobulin (IVIG) and steroids as the first-line treatment for patients. Moreover, antagonists of some cytokines are used as potential future therapeutics. Of note, therapeutic plasmapheresis can be used as a treatment for refractory severe MIS-C. We believe that each patient, especially those with comorbid conditions, should have individualized treatment based on both multidisciplinary consensus approach and expert opinion. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the efficacy of high-dose methylprednisolone (HDP) with intravenous immunoglobulin (IVIG) and conventional prednisolone (CDP) as a first-line therapy in adult patients with immune thrombocytopenia (ITP). Materials and Methods: This retrospective study included 140 adult patients with either previously untreated newly diagnosed ITP (n=51) or persistent or chronic ITP (n=22/n=67)) with episodes. Patients with a platelet count

The exact classification of Kawasaki disease (KD) has been debated. Infectious disease specialists have claimed it as an infection with a classic immune responses to an as yet unidentified pathogen that localizes to the coronary arteries. Others have favored an autoreactive hypothesis that KD is triggered by an antigen that shares homology with structures in the vascular wall, and molecular mimicry resulting in an immune response directed to that tissue. Rheumatologists have classified it as a systemic vasculitis, while some immunologists have stressed the robust nature of the innate immune response that causes both systemic inflammation as well as damage to the coronary arterial wall and questioned whether KD falls within the spectrum of autoinflammatory diseases. This review will describe the evidences available up to now regarding these hypotheses.

Immunoglobulin lots (N = 176) released since March 2020 were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies, with first positive results for September 2020 lots (mean, 1.7 IU/mL; 46% of lots positive). From there, values steadily increased, in correlation with the cumulative coronavirus disease 2019 (COVID-19) incidence, to reach a mean of 31.2 IU/mL and 93% of lots positive by January 2021. Extrapolating the correlation, immunoglobulins could reach an anti-SARS-CoV-2 potency of approximately 345 IU/mL by July 2021. At that stage, prophylactic immunoglobulin treatment for primary/secondary immunodeficiency could contain similar doses of anti-SARS-CoV-2 as convalescent plasma that is used for treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Purpose This report calls attention to the potential risks of diminished kidney function when administering immune globulin (IG). The goal is to increase awareness of chronic kidney disease (CKD) and kidney function impairment in patients receiving IG and provide recommendations for screening, monitoring, and management to promote risk prevention and mitigation. Summary Human IG preparations for intravenous (IVIG) or subcutaneous (SCIG) administration are the mainstay of treatment in patients with primary immunodeficiency diseases. Increasingly, IVIG at high doses (1,000 to 2,400 mg/kg) is also used as a treatment for a variety of autoimmune and inflammatory conditions. Although some autoinflammatory disorders respond to a single course of IVIG therapy, the majority of patients require long-term, regular infusions, thereby increasing the overall risks. Often, both patients and physicians treating adults with IG are unaware of underlying CKD or kidney function impairment. This lack of awareness constitutes a major risk factor for potential worsening, particularly when using high doses of IVIG. Therefore, screening of all patients for CKD and kidney function impairment before the use of IG is essential. Identification of the cause of kidney impairment is strongly encouraged, as IG therapy may need to be modified. Conclusion As detailed here, there are potential risks to patients with impaired kidney function with administration of IG, particularly at high doses. Product selection, volume, route of administration, and rate of infusion may impact those with compromised kidney function. Therefore, screening of all patients for CKD and kidney function impairment before the use of IVIG and SCIG, as well as ongoing monitoring and management, is critical. As with all potential adverse drug reactions, the best approach is to prevent them. [ABSTRACT FROM AUTHOR]

Abstract Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are used in select cases with heparin‐induced thrombocytopenia (HIT). In a cross‐sectional analysis, a propensity matched sample was generated by IVIG or TPE treatment status to assess the primary outcome of mortality. In 500 HIT cases, IVIG or TPE was not associated with increased mortality (OR = 1.46; 95% CI: 0.81–2.63, p = 0.2052) but was associated with a higher likelihood of major bleeding (OR = 1.75; 95% CI: 1.03–2.96, p = 0.0376). The use of IVIG or TPE in HIT cases with bleeding contraindications to standard therapies should be further investigated.

Abstract Histobulin is complementary to IVIG therapy but is an essential therapeutic for PWCD. Histoublin is recommended not only in atopic dermatitis and multiple food allergies but also in patients with multiple allergic diseases.

Primary immunodeficiency (PI) patients may still experience persistent viral and bacterial respiratory infections with ongoing treatments. We report a challenging case of a PI patient who experienced recurrent viral respiratory infections despite receiving standard immunoglobulin replacement therapy. The patient was subsequently managed with immune globulin intravenous, human-slra (ASCENIV™) that contains elevated antibodies against multiple respiratory pathogens. The patient demonstrated significant clinical improvement with a resolution of persistent and debilitating viral respiratory infections and associated sequela. [ABSTRACT FROM AUTHOR]

From September 2020, some immunoglobulin lots from US plasma contained neutralizing antibodies against the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Paralleled by the increasing numbers of post-coronavirus disease 2019 (COVID-19) donors, immunoglobulin lot antibody positivity increased to 93% by January 2021, at a mean titer of approximately 30 IU/mL. The correlation predicted that anti-SARS-CoV-2 potency would reach 345 IU/mL by July 2021. In addition to post-COVID-19 donors, the rapidly increasing number of plasma donors vaccinated against COVID-19 resulted in a mean antibody titer of >600 IU/mL in July 2021 immunoglobulin lots, with SARS-CoV-2 antibody titers for several lots even higher than those of earlier produced hyperimmune globulin products. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov: NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency.

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov : NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency. [ABSTRACT FROM AUTHOR]

Purpose Intravenous immune globulin (IVIG) therapy is used in patients with hypogammaglobulinemia to lower the risk of infections. IVIG and subcutaneous IVIG (SCIG) therapy have been to shown to be safe and effective when administered as clinic-based infusions. Concern from both patients and providers for increased transmission of the coronavirus disease 2019 (COVID-19) virus to immunosuppressed patients with scheduled medical visits and procedures made it necessary for us to reassess our process of how we manage patient care in general and chronic clinic infusions in particular. Here we describe our experience of transitioning patients from clinic-based to home based IVIG and/or SCIG infusions to decrease the risk of COVID-19 exposure. Methods Criteria were developed to identify high-risk immunosuppressed patients who would be appropriate candidates for potential conversion to home based IVIG infusions. Data were collected via chart review, and cost analysis was performed using Medicare Part B reimbursement data. A patient outcome questionnaire was developed for administration through follow-up phone calls. Results From March to May 2020, 45 patients met criteria for home-based infusion, with 27 patients (60%) agreeing to home-based infusion. Posttransition patient outcomes assessment, conducted in 26 patients (96%), demonstrated good patient understanding of the home-based infusion process. No infusion-related complications were reported, and 24 patients (92%) had no concerns about receiving future IVIG and/or SCIG doses at home. No patient tested positive for COVID-19 during the study period. Clinic infusion visits decreased by 26.6 visits per month, resulting in a total of 106 hours of additional available infusion chair time per month and associated cost savings of $12,877. Conclusion Transition of clinic based to home based IVIG/SCIG infusion can be successfully done to decrease potential exposure during a pandemic in a high-risk immunosuppressed population, with no impact on patient satisfaction, adherence, or efficacy. The home-based infusion initiative was associated with a reduction in costs to patients and an increase in available chair time in the infusion clinic. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Kawasaki disease (KD) is a significant febrile illness in children and is the leading cause of acquired pediatric heart disease in developed countries. Its recommended treatment is high‐dose intravenous immune globulin (IVIG) plus aspirin. However, IVIG‐related adverse events are seen frequently in this population. Premedication is commonly used to reduce this risk, but evidence supporting this practice is conflicting. Ultimately, practices vary among institutions and no standard guidelines regarding IVIG premedication currently exist. Methods: Electronic medical records for pediatric patients presenting to an academic, tertiary care medical center diagnosed with KD and who received at least one dose of IVIG were reviewed for: patient demographics, treatment characteristics, premedication use, adverse events, and coronary abnormalities at discharge. Descriptive statistics were used to evaluate study findings. Results: Sixty‐six patients receiving a total of 81 distinct IVIG administrations were evaluated. Most patients (64/66, 97%) were premedicated prior to infusion with 26% of patients (17/66) experiencing an IVIG‐related adverse event, totaling 25 documented adverse events. The most common events included chills and vomiting. Overall, the average duration of hospitalization was 4.37 days. Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities. Conclusion: Practitioners demonstrated a widespread use of premedication for IVIG. However, 26% of patients still experienced an adverse event. While premedication was not shown to have an adverse impact on patient outcomes, it also did not demonstrate a notable reduction from a historic adverse event incidence. [ABSTRACT FROM AUTHOR]

Since December 31, 2019, unknown causes of pneumonia have been reported in Wuhan, China. This special pneumonia associated with a novel coronavirus was named 2019‐nCoV by the World Health Organization (WHO) in January 2020. From the beginning of this infectious disease, clinicians and researchers have been endeavoring to discover an effective and suitable treatment for affected patients. To date, there is no definitive and specific treatments for coronavirus disease‐19 (COVID‐19) infection while drugs introduced are still in the clinical trial phase. Intravenous immune globulin (IVIG) is a biological product prepared from the serum and an optional treatment for patients with antibody deficiencies. In many countries, much attention has been paid to the use of IVIG in the treatment of patients with COVID‐19. Due to the therapeutic importance of IVIG in virus infections, in the current study, we reviewed the possible effect of IVIG in viral infections and potential evidence of IVIG therapy in patients with COVID‐19 virus. [ABSTRACT FROM AUTHOR]

Histobulin is complementary to IVIG therapy but is an essential therapeutic for PWCD. Histoublin is recommended not only in atopic dermatitis and multiple food allergies but also in patients with multiple allergic diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Irrational drug use is a global health challenge in all healthcare settings, such as hospitals. This study evaluated the impact of an intervention by the pharmaceutical care unit on the use pattern of high-value medications and their direct costs in a referral hospital. Methods This interventional, prospective study was carried out in clinical wards of Namazi Hospital (Shiraz University of Medical Sciences) during six months from May 2015 to October 2015. Clinical pharmacists completed the checklists for albumin, intravenous (IV) pantoprazole, and IV immune globulin (IVIG), as three high-cost medications. When ordering these medications, the physicians were asked to complete the checklists. Then, trained pharmacists examined the checklists, based on the clinical and paraclinical conditions. Results The total number of administered medications and their relative cost decreased by 50.76% through guideline implementation; the difference was significant (P

Abstract Background Healthcare delivery organizations face increasing pressure to manage the use of medications in terms of safety, waste reduction, and cost containment. Objective To describe a computerized provider order entry (CPOE) system intervention to optimize use of a commonly ordered, high‐cost therapeutic: intravenous immune globulin (IVIG). Design Description of IVIG order configuration, medication use patterns, and subsequent order set configuration development in a CPOE system. Measurements IVIG orders were extracted from the CPOE system before and after the implementation of a specialty orderset to determine the indications for use, dosing, and duration of therapy. Orders were compared to a theoretical dosing schedule created from published evidence and data from a prior medication use evaluation. Results During 36 months before the implementation of the IVIG order set, 1965 IVIG orders were reviewed. The prescribed IVIG dose varied considerably from the expected dose (mean = −1.8, range = −4.9‐1.5). In the 27 months after order set implementation, 848 IVIG orders were reviewed. The prescribed IVIG dose was closer to the expected dose (mean = −1.2, range = −3.9‐2.6, P

Introduction: Although intravenous immune globulin (IVIg) is used to treat patients in the outpatient setting, there is limited documentation addressing the safety of this practice.Methods: Retrospective analysis of 438 patients with neuromuscular diseases receiving IVIg in an outpatient setting.Results: Adverse events (AE) overall occurred in 16.9% of patients. Headache was the most common AE, noted in 11.6% of patients. Serious AEs occurred in 0.91% of patients; aseptic meningitis was the only one noted. Multivariate analyses identified the following risk factors for AEs: first-lifetime course of IVIg, higher dose per course of IVIg, diagnosis of myasthenia gravis, women, and younger age.Discussion: Intravenous immune globulin is generally safe to administer in an outpatient setting. Women, myasthenia gravis patients, and those receiving their first course or a higher total dose of IVIg are at an increased risk of experiencing an AE. [ABSTRACT FROM AUTHOR]

Background: Healthcare delivery organizations face increasing pressure to manage the use of medications in terms of safety, waste reduction, and cost containment. Objective: To describe a computerized provider order entry (CPOE) system intervention to optimize use of a commonly ordered, high‐cost therapeutic: intravenous immune globulin (IVIG). Design: Description of IVIG order configuration, medication use patterns, and subsequent order set configuration development in a CPOE system. Measurements: IVIG orders were extracted from the CPOE system before and after the implementation of a specialty orderset to determine the indications for use, dosing, and duration of therapy. Orders were compared to a theoretical dosing schedule created from published evidence and data from a prior medication use evaluation. Results: During 36 months before the implementation of the IVIG order set, 1965 IVIG orders were reviewed. The prescribed IVIG dose varied considerably from the expected dose (mean = −1.8, range = −4.9‐1.5). In the 27 months after order set implementation, 848 IVIG orders were reviewed. The prescribed IVIG dose was closer to the expected dose (mean = −1.2, range = −3.9‐2.6, P < .0001). Conclusions: Order configuration processes are cumbersome and time‐consuming, but can be streamlined to enhance a medication’s usage in the healthcare system. A better understanding of institution‐specific ordering patterns may facilitate more efficient and effective order configuration and optimize drug use. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity. Two hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded. Mean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05). In our study, in females and in patients without any history of past infection, platelet count >20 × 109/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature. [ABSTRACT FROM AUTHOR]

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6 months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation. [ABSTRACT FROM AUTHOR]

The presence of residual activated coagulation factor XI (FXIa) in some commercial intravenous immunoglobulin (IVIG) products has been identified as the root cause of a small number of thromboembolic events in patients who had received such therapy. Our objectives here were to design and evaluate the manufacturing process of GC5107, a 10% glycine-stabilized IVIG product, for its capacity to remove FXIa. The manufacturing process included a cation exchange chromatography (CEX) step, which employs a resin that binds immunoglobulin G (IgG) with high capacity. Procoagulant activity was assessed using Western blot analysis, enzyme-linked immunosorbent assay, thrombin generation assay, chromogenic FXIa assay, and non-activated partial thromboplastin time (NaPTT) assay. A spiking study in which large quantities of FXIa were added to samples before CEX chromatography was used to examine the robustness of the process to remove FXIa. Western blot and ELISA analyses demonstrated that residual FXIa remained in the intermediate manufacturing products until after CEX chromatography, when it was reduced to undetectable levels. The spiking study demonstrated that CEX chromatography removed >99% of FXI protein and reduced FXI activity to below detection limits, even in samples containing 158-fold greater FXIa levels than that of normal samples. Procoagulant activity in 9 consecutive lots of GC5107 was reduced to below the detection limits of the thrombin generation and chromogenic FXIa assays (<1.56 IU/ml and <0.16 IU/ml, respectively). The NaPTT of >250 s in all 9 lots indicated very low levels of procoagulant activity. We demonstrate that a novel 10% IVIG manufacturing process including CEX chromatography is a robust means of removing FXIa from the final preparation., Competing Interests: GK, JL, M-JK, EB, JH and SP are salaried employees of GC Biopharma Corporation. AH is a salaried employee of GC Biopharma USA Inc., (© 2023 Kang, Huber, Lee, Kim, Bang, Hong and Park.)

Introduction: Cost of illness studies are essential to estimate societal costs of chronic inflammatory demyelinating polyneuropathy (CIDP) and identify cost-driving factors.Methods: In total, 108 patients were recruited from 3 specialized neuroimmunological clinics. Costs were calculated for a 3-month period, including direct and indirect costs. The following outcomes were assessed: inflammatory neuropathy cause and treatment disability scale, Mini-Mental State Examination, Beck Depression Inventory, Charlson comorbidity index, EuroQol-5D, World Health Organization quality of life instrument, and socioeconomic status. Univariate and multivariate analyses were applied to identify cost-driving factors.Results: Total quarterly costs were €11,333. Direct costs contributed to 83% of total costs (€9,423), whereas indirect costs accounted for 17% (€1,910) of total costs. The cost of intravenous immunoglobulin (IVIg) was the main determinant of total costs (67%). Reduced health-related quality of life and depressive symptoms were identified as independent predictors of higher total costs.Discussion: CIDP is associated with high societal costs, mainly resulting from the cost of IVIg treatment. Muscle Nerve 58: 681-687, 2018. [ABSTRACT FROM AUTHOR]

Recurrent embryo implantation failure is a disorder with potentially dreadful physiological and psychological manifestations for those who are affected. Embryo implantation and formation of a functional placenta are processes that require a plethora of regulatory mechanisms involving both maternal and embryonic cells. In the ensuing overview, an attempt is made to understand (1) the pathophysiology of recurrent unexplained implantation failure (2) the available evidence for the two popular treatment modalities, i.e., intravenous immune globulin and intralipid, (3) the limitation of current available data, (4) the pathophysiology and immunomodulatory treatment options for recurrent implantation failure to address the pathological, psychological, and financial distress, and associated impact on couple's quality of life. [ABSTRACT FROM AUTHOR]