Jason Tay

Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series

Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII deficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagulation test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcutaneous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in patients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobulin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvious lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients (27%) having partial resolution; 9 of these patients (14%) had a relapse. Thirteen patients (20%) died (7 from internal hemorrhage). Completeness of reporting varied for specific CAse REport items. Patient demographics, clinician-assessed outcomes, and laboratory test results were reported in all case reports. Least reported items included informed consent (6%), patient perspective (3%), and a title containing the words case report (9%). Our systematic review provides the most complete overview of published reports of FXIII acquired inhibitor to date. There is a paucity of data available on FXIII acquired inhibitor, and the available data may be limited by variable reporting. Despite multimodal therapy, a significant proportion of patients with FXIII acquired inhibitor have a large burden of morbidity and mortality.

A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers

Infection remains one of the most common transplant‐related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non‐uniform practice in the use of Ig treatment. We aimed to survey lead transplant practitioners for current practice around polyvalent Ig use in post‐transplant recipients across Canada.

Network geometry of evidence from randomised controlled trials addressing donor selection and source of haematopoietic progenitor cells used in allogeneic transplantation: a systematic scoping review: RCT evidence network of cell source in HCT

A scoping review of randomised controlled trials (RCTs) addressing source of cells and choice of donor for allogeneic haematopoietic cell transplantation (HCT) was performed to create a network of best evidence that allows us to identify new potential indirect comparisons for the strategic development of future studies that connect to the existing evidence network.

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis: IMMUNOGLOBULIN PROPHYLAXIS IN HSCT

Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients.

Early Relapse for Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Therapy: A Single-center Experience

Introduction Multiple myeloma is a heterogeneous disease with diverse clinical courses and patient outcomes. Although the introduction of novel agents has improved the overall survival (OS) of multiple myeloma patients, reports have highlighted that a subset of patients persists who experience early relapse (ER) and whose prognosis is significantly poorer than that of patients with a longer therapy response. Methods The purpose of the present study was to understand the effect of ER on OS and identify other predictors of OS. We analyzed the outcomes of 257 patients who had undergone novel agent‐based induction and single autologous stem cell therapy at our center from 2010 to 2016. Results ER occurred in 35 patients (13.6%), and the group had a greater percentage of high‐risk cytogenetics (48.5% vs. 23.3%; P = .0001), a lower percentage of a very good partial response or better (51.4% vs. 80.5%; P = .001), and a shorter median OS (17.8 months vs. not realized; P = .0001) compared with the non‐ER group. Multivariate analysis showed that the presence of ER, high‐risk cytogenetics, and lactate dehydrogenase > 350 UI/L are independent prognosticators for OS (P < .05). Conclusions Our results have demonstrated that ER is an important clinical indicator of patients at high risk. As applications of novel agents evolve, further studies are required to tailor therapy for this patient group. Micro‐Abstract The purpose of the present study was to understand the effect of early relapse (ER) on the overall survival of myeloma patients. We analyzed the outcomes of 257 patients who had received novel agent‐based induction therapy and undergone single autologous stem cell therapy at our center from 2010 to 2016. We have concluded that ER, high‐risk cytogenetics, and lactate dehydrogenase > 350 UI/L are significant prognosticators for poor patient outcome in those with multiple myeloma.

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study

Introduction In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue—haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding. Methods and analysis This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3–5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses. Ethics and dissemination This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by the Ottawa Health Science Network Research Ethics Board. Study results will presented at national and international conferences. Importantly, the results of this trial will inform the feasibility and conduct of a larger study. Trial registration number NCT02650791; Pre-results.