Comparison of the solid-phase red cell adherence assay and tube method for detection and identification of red blood cell antibodies.

OBJECTIVES: Identifying antibodies to red blood cell antigens is one of transfusion medicine's critical responsibilities. The International Society of Blood Transfusion recognizes 354 red blood cell antigens. Accurate identification of clinically significant alloantibodies is imperative for preventing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We compared the performance of the tube (polyethylene glycol-indirect antiglobulin test [PEG-IAT]) and solid-phase red cell adherence assay techniques. METHODS: We performed a retrospective study on all antibody screens performed between 2007 and 2021 at Stanford Transfusion Services. Initially, 631,535 antibody screens were performed using a solid-phase technique. Subsequent antibody identifications were performed using a combination of tube testing and solid-phase techniques. RESULTS: Antibody screening resulted in 28,316 (4.5%) positive samples. Antibody identification performed on both platforms identified 50 discordant samples. The anti-E antibody had the lowest sensitivity (98.99%) in the automated solid-phase technique, while anti-Jkb had the lowest sensitivity (98.78%) with the PEG-IAT method. CONCLUSIONS: To our knowledge, this is the first robust, 15-year study comparing methodologic sensitivity to detect clinically significant alloantibodies. The incidence of discordant results between PEG-IAT and the solid-phase technique was low. Among discordant samples, anti-Jka was commonly detected using the solid-phase method but not with the PEG-IAT. In contrast, anti-E was commonly detected by PEG-IAT but not by the solid-phase method.

Incidence of formation of anti-D between patients with and without a history of solid organ transplant.

BACKGROUND AND OBJECTIVES: Solid organ transplant surgeries including liver transplants constitute a substantial risk of bleeding complications and given frequent national blood shortages, supporting D-negative transplant recipients with D-negative red blood cell products perioperatively can be difficult for the transfusion services. This study was designed to compare the incidence of alloimmunization after D-mismatched red cell transfusions between patients with and without a history of solid organ transplant at a single tertiary care hospital. The patients undergoing solid organ transplants are on strong immunosuppressive regimens perioperatively to help reduce the risk of rejection. We hypothesized that the use of these immunosuppressive agents makes these patients very less likely to mount an immune response and form anti-D antibodies when exposed to the D-positive red blood cell products perioperatively. STUDY DESIGN AND METHODS: At our center, D-negative patients who received ≥1 unit of D-positive red blood cell products were identified using historical transfusion records. Antibody testing results were examined to determine the incidence of the formation of anti-D and any other red cell alloantibodies after transfusion and these results were compared between patients with and without a history of solid organ transplant. RESULTS: We were able to identify a total of 22 patients over 10 years with D-negative phenotype who had undergone a solid organ transplant and had received D-positive red blood cell products during the transplant surgeries. We also identified a second group of 54 patients with D-negative phenotype who had received D-positive red blood cell products for other indications including medical and surgical. A comparison of the data showed no new anti-D formation among patients with a history of D mismatched transfusion during solid organ transplant surgeries. CONCLUSION: Among our limited study population, we observed a very low likelihood of D alloimmunization among solid organ transplant recipients. A larger, prospective study could help further evaluate the need for prophylactic D matching for red cell transfusions during solid organ transplant surgeries.

Plasma Exchange in Patients With Myositis due to Immune Checkpoint Inhibitor Therapy.

ABSTRACT: Immune checkpoint inhibitors used to treat malignancies may lead to various immune-related adverse events (irAEs) including conditions such as myositis and myasthenia gravis (MG). Here, we describe 2 cases of myositis treated effectively with therapeutic plasma exchange (PLEX). A 64-year-old man with thymic cancer developed leg weakness and dyspnea 1 month after the second dose of nivolumab with moderate weakness in proximal and distal muscles, with elevated creatine kinase levels. Another 77-year-old man with Stage IIIB squamous cell carcinoma of the lung developed progressive proximal muscle weakness and became nonambulatory after cycle 2 of durvalumab with persistently high creatine kinase levels despite prednisone treatment. Electrophysiology revealed irritative myopathy without evidence of neuromuscular junction dysfunction and MG antibody testing was nonrevealing. With PLEX, both patients noticed rapid improvement in strength. PLEX in conjunction with other immunosuppressive agents can result in rapid improvement in irAE-myositis even in patients without associated MG.

Updates on the mobilization pipeline for hematopoietic stem cell collection.

Hematopoetic Stem Cell Transplantation is a life saving procedure which requires mobilization of stem cells for apheresis procedure. In this review we aimed to examine mobilizing agents that are in use and under investigation. Apheresis practitioners who oversee stem cell collections should be familiar with the recent advances in mobilization agents to utilize most up-to-date information for better patient outcomes.

A single center experience for clinical evaluation of paroxysmal cold hemoglobinuria and Donath-Landsteiner testing.

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare form of autoimmune hemolytic anemia (AIHA), mainly affecting children. The diagnosis and management are challenging due to similarities to other causes for AIHA and limited availability to Donath-Landsteiner (DL) testing. STUDY DESIGN AND METHODS: In this single-center retrospective study, we aimed to characterize the clinical presentation and outcomes of PCH patients, defined as having positive Donath-Landsteiner antibodies, compared to a cohort of AIHA patients. RESULTS: DL-positive patients were observed to have higher lactate dehydrogenase levels and lower reticulocyte counts compared to DL-negative patients, although this was not statistically significant. We also observed that using steroids in DL-positive patients did not significantly impact their recovery. DISCUSSION: Our findings support the limited published data on PCH patients and further prompt larger multicenter studies to further characterize these patients so that they are more readily identified, especially in centers where DL antibody testing is not readily available.

Neonatal Fc receptor blockade as emerging therapy in diseases with plasma exchange indications.

Neonatal Fc receptor (FcRn) blockade may represent a mechanism similar to plasma exchange (PLEX) in reducing immunoglobulin levels and thus have a broad implication for apheresis practitioners. Although only efgartigimod received FDA approval for myasthenia gravis in December 2021, multiple trials are currently underway with different FcRn therapies in a varied group of IgG antibody-mediated neurological and hematological disorders which are outlined in this review. In this review we discuss FcRn's mechanism of action, and its potential use in various neurological and non-neurological diseases. In addition, we further compare the kinetics and adverse events of PLEX and FcRn blockade. We encourage apheresis practitioners to be familiar with this class of drugs in order to better understand how these two therapies can be used either standalone, or in combination with other therapies as both FcRn antagonism and PLEX improve clinical state by reducing IgG levels and pathogenic antibodies.

Plasma Exchange in Alzheimer's Disease.

Therapeutic plasma exchange (TPE) has traditionally been used to selectively remove pathologic contents including autoantibodies, abnormal proteins, immune complexes, or toxins from a patient's plasma. In addition to the removal of molecular contributors to disease, fluid replacement and infusion of beneficial plasma constituents including albumin can be tapered based on the pathophysiologic mechanisms of the offending disease. This treatment modality has shown efficacy in symptomatic relief and slowing of disease progression for various neurologic, immunologic, and hematologic diseases. This review outlines the rationale for TPE in the treatment of Alzheimer's Disease (AD) through a potential mechanism leveraging the concentration gradient of amyloid ß peptides and the infusion of albumin, and critically reviews the clinical evidence for treatment of AD using TPE and albumin replacement. This review also highlights potential sources of bias that must be considered in conjunction with the evidence of efficacy for the use of TPE in AD.

Plasma exchange for severe immune-related adverse events from checkpoint inhibitors: an early window of opportunity?

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several advanced malignancies leading to durable remission in a subset of patients. Their rapidly expanding use has led to an increased frequency of immune-related adverse events (irAEs). The pathogenesis of irAEs is poorly understood but may involve aberrant activation of T cells leading to inflammatory cytokine release or production of pathogenic antibodies leading to organ damage. Severe irAEs can be extremely debilitating and, in some cases, life threatening. IrAEs may not always be corticosteroid responsive or may require excessively high, often toxic, corticosteroid doses. Therapeutic plasma exchange (PLEX) is a treatment modality that has shown promising results for the management of certain severe irAEs, including irAEs that are not mentioned in current treatment guidelines. PLEX may attenuate ongoing irAEs and prevent delayed irAEs by accelerating clearance of the ICI, or by acutely removing pathogenic antibodies, cytokines, and chemokines. Here, we summarize examples from the literature in which PLEX was successfully used for the treatment of irAEs. We posit that timing may be a critical factor and that earlier utilization of PLEX for life-threatening irAEs may result in more favorable outcomes. In individuals at high risk for irAEs, the availability of PLEX as a potential therapeutic mitigation strategy may encourage life-saving ICI use or rechallenge. Future research will be critical to better define which indications are most amenable to PLEX, particularly to establish the optimal place in the sequence of irAE therapies and to assess the ramifications of ICI removal on cancer outcomes.

Herpes hepatitis as a complication of total abdominal hysterectomy; an unusual complication of abdominal instrumentation.

Herpes simplex virus hepatitis is a rare but potentially fatal disease without early intervention. Impaired immunity is a major predisposing risk factor but infection in immunocompetent individuals is not unheard of. Diagnosis is complicated by its rarity and nonspecific signs and symptoms on presentation. Identification by liver biopsy is often limited due to concurrent coagulopathy. Early and aggressive treatment is centered on antiviral therapy with acyclovir. We present a case of herpes hepatitis in an immunocompetent woman following abdominal instrumentation.

Intravascular large B-cell lymphoma presenting as multiple stroke: A case report.

INTRODUCTION: Intravascular large B-cell lymphoma (IVLBCL) is an uncommon disease with a poor prognosis if not diagnosed early. It can present with central nervous system (CNS) manifestations. The diagnosis of IVCBCL is difficult to make given its varied clinical manifestations and the lack of a specific diagnostic modality. CASE PRESENTATION: We report an interesting case of IVLBCL presenting as bilateral strokes. The diagnosis was made by a random skin biopsy, which confirmed IVLBCL. The patient was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).Neurological symptoms improved with R-CHOP. Repeat magnetic resonance imaging (MRI) of the brain showed improvement of the prior lesions. CONCLUSION: IVLBCL is an aggressive disease with high mortality. Timely diagnosis and treatment can be lifesaving.

Primary malignant melanoma of the lung: a case report of a rare tumor and review of the literature.

Primary malignant melanoma of the lung (PMML) is a rare malignancy that exhibits aggressive behavior and has a very poor prognosis. We are reporting on a case of PMML in an otherwise healthy 22-year-old Caucasian male with no significant past medical history and an unremarkable family history. The patient initially presented with a 2-month history of a cough and an unexplained 22-lb weight loss. His initial chest X-ray demonstrated opacification of the right lower lobe (RLL) of his lung and a subsequent computerized tomography scan (CT scan) of his lung revealed a large mass occupying most of his RLL (Figure 1). The patient subsequently underwent a bronchoscopy with endobronchial ultrasound. Biopsies revealed a poorly differentiated carcinoma. A positron emission tomography with low dose CT scan was performed per protocol and revealed an intensely hypermetabolic tumor with no evidence for lymphatic disease or extra-thoracic spread. The patient underwent a surgical exploration and a right lower lobectomy with a thoracic lymphadenectomy. The pathology including immunohistochemical stains demonstrated a malignant melanoma with no lymph node involvement. A physical examination including ophthalmic, mucosal, and skin examinations revealed no evidence for an extra-thoracic site of the disease. The patient had negative margins for resection and did not receive any adjuvant therapy and is alive and well with no evidence for recurrence 3 years after the resection.

A case report on 2 unique presentations of upper extremity deep vein thrombosis.

RATIONALE: Thoracic outlet syndrome (TOS) is a rare cause of upper extremity deep vein thrombosis (UEDVT). The treatment usually involves catheter directed thrombolysis followed by systemic anticoagulation. Surgical decompression is frequently recommended after anticoagulation for definitive therapy. PATIENT CONCERNS: We report two cases of UEDVT secondary to venous TOS with important clinical presentations. DIAGNOSES: Venous TOS. INTERVENTIONS: One patient was initially treated conservatively but had a recurrent UEDVT. The second patient had a residual stump from a prior rib resection that was causing compression on the subclavian vein, resulting in recurrent venous symptoms. OUTCOMES: Both patients achieved significant improvement in their symptoms at 1 year follow-up. LESSONS: UEDVTs can be debilitating, and may limit activities of daily living. Surgical decompression may offer significant improvement in quality of life and symptom relief in such patients.

One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity.

BACKGROUND: One of the most important problems in finding blood donors is the inadequacy of volunteer number. To overcome this problem, one of the solutions we suggest is innovating new health benefits of blood donation. The aim of the present study is to investigate the effects of blood donation on oxidative status markers and acute-phase reactants. METHODS: A total of 96 healthy volunteers were recruited into the study. Blood samples were withdrawn 5 min before and 24 h after the blood donation. Serum nitric oxide, malondialdehyde levels, and activity of superoxide dismutase and myeloperoxidase were measured spectrophotometrically. Serum levels of high-sensitive C-reactive protein and pentraxin-3 as acute-phase reactants were measured by enzyme-linked immunosorbent assay kits. RESULTS: We found statistically significant lower pentraxin-3 and high-sensitive C-reactive protein levels and higher superoxide dismutase activity and nitric oxide level 24 h after blood donation in serum of blood donor when compared with before blood donation. CONCLUSIONS: These findings suggest that blood donation affected oxidative status and acute-phase reactants in donors. Blood donation removes oxidants and decreases oxidative stress by elevating antioxidant enzyme such as superoxide dismutase. This is one more health benefit or reason why we should donate blood. Further large-scale studies should evaluate this mechanism and compare the same effect of wet cupping therapy.

Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study.

BACKGROUND: T-cell large granular lymphocytic leukaemia (T-LGL) is a lymphoproliferative disease that presents with immune-mediated cytopenias and is characterised by clonal expansion of cytotoxic CD3+ CD8+ lymphocytes. Use of methotrexate, ciclosporin, or cyclophosphamide as first therapy improves cytopenias in 50% of patients, but long-term use of these can lead to toxicity. We aimed to explore the activity and safety of alemtuzumab, an anti-CD52 monoclonal antibody, in patients with T-LGL. METHODS: We did this single-arm, phase 2 trial in consecutively enrolled adults with T-LGL referred to the National Institutes of Health in Bethesda, MD, USA. Alemtuzumab was given intravenously at 10 mg per day for 10 days. The primary endpoint was haematological response at 3 months after infusion. A complete response was defined as normalisation of all affected lineages, and a partial response was defined in neutropenic patients as 100% increase in the absolute neutrophil count to more than 5 × 10(8) cells per L, and in those with anaemia, as any increase in haemoglobin of 20 g/L or higher observed in at least two serial measurements 1 week apart and sustained for 1 month or longer without exogenous growth factors support or transfusions. Analysis was by intention to treat. We report results from the first stage of this Simon two-stage design trial; enrolment into the second stage is continuing. This study is registered with ClinicalTrials.gov, number NCT00345345. FINDINGS: From Oct 1, 2006, to March 1, 2015, we enrolled 25 patients with T-LGL. 14 patients (56%; 95% CI 35-76) had a haematological response at 3 months. Four patients with associated myelodysplastic syndrome and two who had received haemopoietic stem cell transplantation had either no response or were not evaluable, meaning 14 (74% [49-91]) of the 19 patients with classic T-LGL responded. All patients had an infusion reaction (24 [96%] patients grade 1-2, one [4%] patient grade 3), which improved with symptomatic therapy. All patients developed lymphopenia, with 22 (88%) patients having grade 3 or 4 lymphopenia. The other most common grade 3 and 4 adverse events were leukopenia (eight [32%]) and neutropenic infections (five [20%]). Seven patients died; all were non-responders. INTERPRETATION: This is the largest and only prospective study of alemtuzumab in patients with T-LGL. The activity reported with a single course of a lymphocytotoxic drug in patients with mainly relapsed and refractory disease suggests that haematological response can be achieved without continued use of oral immunosuppression. FUNDING: National Heart, Lung, and Blood Institute.

Antioxidant signal and kidney injury molecule-1 levels in shockwave lithotripsy induced kidney injury.

PURPOSE: Shockwave lithotripsy (SWL) induces acute kidney injury (AKI) that extends from the papilla to the outer cortex by causing ischemia and the production of nephrotoxic agents. Direct ischemic damage and the generation of free radicals cause injury to the proximal tubular cells. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is upregulated in proximal tubular cells after ischemic or nephrotoxic injury and is not expressed in healthy kidneys. We evaluated the extent of free radical production in response to SWL by measuring urinary total antioxidant capacity (TAC) and total oxidant status (TOS). Furthermore, we investigated the severity of SWL-induced kidney injury by measuring KIM-1 expression levels. PATIENTS AND METHODS: The study population comprised 30 patients who were carefully selected and 30 age and sex matched control subjects. All patients received the same SWL procedure. Midstream urine samples were collected from patients before SWL and at 120 minutes after SWL. Urine KIM-1 levels were measured by enzyme-linked immunosorbent assay, and TAC and TOS were measured via spectrophotometry. RESULTS: Mean levels of TAC (2.88±0.56 mmolTxEq/L),TOS (8.27±1.57 µmolH2O2Eq/L), and KIM-1 (0.55±0.08 ng/mL) before SWL were not significantly different from mean TAC, TOS, and KIM-1 levels measured from the control group at 2.81±0.42 mmolTxEq/L, 10.73±1.4 µmolH2O2Eq/L, and 0.51±0.07 ng/mL, respectively. Two hours after SWL, mean urine TAC levels (2.81±0.85 mmolTxEq/L, P=0.02) were decreased and mean KIM-1 expression (0.85±0.11 ng/mL, P=0.01) was significantly increased, but there was no significant difference in mean TOS levels (11.24±1.9 µmolH2O2Eq/L, P=0.627) compared with the control group. CONCLUSIONS: The increased burden of free radical oxidants in the setting of decreasing antioxidant capacity may be one of the initial indicators of AKI after SWL. Moreover, KIM-1 demonstrates great potential as an early and noninvasive biomarker of SWL-induced kidney injury.

Prognostic factors in first-line chemotherapy treated metastatic gastric cancer patients: a retrospective study.

BACKGROUND: The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy. METHODS: We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses. RESULTS: Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables. CONCLUSION: Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.