Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Clinical characterization and hematopoietic stem cell transplant outcomes for congenital sideroblastic anemia caused by a novel pathogenic variant in SLC25A38.

BACKGROUND: Congenital sideroblastic anemia (CSA) constitutes an uncommon category of inherited anemia often associated with pathologic iron accumulation. Pathogenic variants in several genes have been identified as causative for CSA. Autosomal recessive pathogenic variants in the mitochondrial glycine transporter SLC25A38 have been implicated in a subset of patients with CSA. PROCEDURE: We describe seven individuals of Canadian Cree descent with a known or inferred homozygous novel founder missense variant in SLC25A38 (c.560G>A, p.Arg187Gln). RESULTS: All individuals presented as young children (median age 6 months) with severe microcytic, hypochromic anemia associated with pretransfusion iron overload, requiring red cell transfusion support and iron chelation. Six individuals received pyridoxine supplementation; two demonstrating transient partial responses. Three individuals underwent allogeneic hematopoietic stem cell transplantation (HSCT). One individual with significant iron loading died in the posttransplant period due to complications of sepsis. The other two individuals remain transfusion-free following HSCT. CONCLUSIONS: Despite a common genetic etiology, phenotypic variability was noted in this cohort. A transient response to pyridoxine was noted in two individuals but should not be considered a long-term therapeutic strategy. HSCT was curative when performed before significant iron loading occurred. Early identification of CSA and timely HSCT can result in excellent long-term outcomes.

Cold agglutinin disease complicating management of aortic dissection.

BACKGROUND: Cold agglutinin disease is characterized by acrocyanosis, hemolytic anemia, and occasionally, frank hemoglobinuria. Although cold agglutinins are commonly detected, they are rarely clinically significant due to subphysiologic temperatures at which agglutination occurs. Cardiovascular surgical procedures requiring hypothermia present a unique challenge for these patients, requiring modification of the conduct of cardiopulmonary bypass and cardioplegia. CASE REPORT: Herein we report a case of a patient with a prior history of symptomatic cold agglutinin disease and type A aortic dissection, presenting with dilation of his known diseased ascending aorta, requiring semi-urgent repair. The patient underwent plasma exchange on two successive days preceding surgery to reduce the cold agglutinin titre. A modified Bentall procedure and replacement of ascending aorta and hemiarch under deep hypothermic circulatory arrest was performed without complication. CONCLUSIONS: This case demonstrates the efficacy of employing plasma exchange in preparation for cardiac surgery with deep hypothermic circulatory arrest in a patient with clinically significant cold agglutinin disease. Plasma exchange alone may be sufficient in preparing patients with cold agglutinin disease for procedures requiring significant hypothermia when the delayed onset of action of alternative therapies is not acceptable. Choice of replacement fluid is critical in ensuring maintenance of coagulation proteins perioperatively and minimizing complement activation.

A Pharmacist-Managed Hydroxyurea Prescribing Protocol Improves Uptake and Optimization among Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a common genetic disorder with potentially serious sequelae that can be effectively treated with hydroxyurea. Despite its favorable benefit-risk profile, hydroxyurea uptake in patients with SCD is low. A pilot study was conducted at the Southern Alberta Rare Blood and Bleeding Disorders (SARBBDs) Comprehensive Care Program between January 2020 and September 2023 to assess the implementation of a pharmacist-led protocol for supporting the uptake of hydroxyurea among eligible patients with SCD and optimizing its dosing. The protocol standardized the prescription, monitoring, dose titration, and patient counselling by a clinic pharmacist. The number of patients enrolled in the SARBBDs program increased from 98 in January 2020 to 168 in 2023. During this period, the proportion of patients on hydroxyurea increased from 37.8% to 62.5%, the proportion of patients on hydroxyurea who were at a maximum tolerated dose (MTD) increased from 35.1% to 63.8%, and the average hemoglobin F level increased from 13.9% to 19.7%. The mean time to reach MTD was 10 months and required eight pharmacist interventions, six laboratory assessments, and three dose increases. Hydroxyurea continuation rates were high, with most discontinuations resulting from loss to follow-up or transition to a transfusion management strategy. This real-world pilot study demonstrated that implementation of a pharmacist-led prescribing and monitoring protocol nearly doubled hydroxyurea uptake and achievement of MTD in patients with SCD managed in a rare blood disorders clinic.

Clinical Outcomes in a Large Canadian Centralized CLL Clinic Based on Treatment and Molecular Factors over a Decade.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton's tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.

Efficacy and Safety of Tranexamic Acid in Major Non-Cardiac Surgeries at High Risk for Transfusion: A Systematic Review and Meta-Analysis.

Tranexamic acid (TXA) reduces transfusion requirements in cardiac surgery and total hip and knee arthroplasty, where it has become standard of care. Our objective is to determine the efficacy and safety of TXA in other surgeries associated with a high risk for red blood cell (RBC) transfusion. We identified randomized controlled trials in Medline, Embase, CENTRAL, and CAB abstracts from inception to June 2019. We included trials evaluating intraoperative IV TXA in adult patients undergoing a non-cardiac and non-hip and knee arthroplasty surgeries at high-risk for RBC transfusion, defined as a baseline transfusion rate ≥5% in comparator arm. We assessed risk of bias using the Cochrane Risk of Bias tool. We used GRADE methodology to assess certainty of evidence. From 8565 citations identified, we included 69 unique trials, enrolling 6157 patients. TXA reduces both the proportion of patients transfused RBCs (relative risk (RR) 0.59; 95% confidence interval (CI) 0.48 to 0.72; low certainty evidence) and the volume of RBC transfused (MD -0.51 RBC units; 95%CI -0.13 to -0.9 units; low certainty evidence) when compared to placebo or usual care. TXA was not associated with differences in deep vein thrombosis, pulmonary embolism, all-cause mortality, hospital length of stay, need for re-operation due to hemorrhage, myocardial infarction, stroke or seizure. In patients undergoing a broad range of non-cardiac and non-hip and knee arthroplasty surgeries at high risk for RBC transfusion, perioperative TXA reduced exposure to RBC transfusion. No differences in thrombotic outcomes were identified; however, summary effect estimates were limited by lack of systemic screening and short duration of follow-up.

A Case of Waldenstrom's Macroglobulinemia Morphologically Resembling Plasma Cell Myeloma.

Although both are characterized by the presence of an IgM monoclonal gammopathy, IgM multiple myeloma and Waldenstrom's macroglobulinemia are two distinct hematologic entities. Differentiation of each however, may be challenging, but obviously critical to ensuring appropriate therapeutic decision-making and patient prognostication. Herein we report a case of a patient with Waldenstrom's macroglobulinemia presenting with bone marrow morphology mimicking plasma cell myeloma, highlighting the importance of clinical correlation and ancillary studies to reach an appropriate diagnosis.

Midterm outcomes after postoperative delirium on cognition and mood in patients after cardiac surgery.

OBJECTIVE: Delirium is a common neurologic complication after cardiac surgery. Our primary objective was to determine the impact of delirium on self-reported problems with midterm cognitive functioning and mood postcardiac surgery. METHODS: A single-center, prospective cohort study was conducted, enrolling 197 patients undergoing coronary artery bypass grafting or valve replacement. Baseline cognition and mood were assessed preoperatively in elective patients as a part of routine care using the Montreal Cognitive Assessment and Patient Health Questionnaire 9, respectively. During hospitalization, delirium was diagnosed using the Confusion Assessment Method (Confusion Assessment Method/Confusion Assessment Method Intensive Care Unit). Follow-up assessments were carried out via telephone interview at 6 to 9 months after cardiac surgery using the EuroQoL-5D, Patient Health Questionnaire 9, Alcohol Use Disorders Identification Test Consumption, Memory Impairment Screen, and Category Fluency Test assessments. We examined resultant scores in the domains of cognition and mood among delirious and nondelirious cohorts, controlling for confounders deemed clinically relevant. RESULTS: A total of 197 patients were enrolled in the study, of whom 44 (22%) developed postoperative delirium. After adjustment, no differences were observed in cognitive functioning between the delirious and nondelirious subjects after 6 to 9 months. However, delirious patients were more likely to experience self-reported problems in affective (depression and anxiety) functioning as measured by the EuroQoL-5D (odds ratio, 4.41; 95% confidence interval, 1.51-12.92; P < .01). CONCLUSIONS: Postoperative delirium is associated with increased anxiety and depression at 6 to 9 months postcardiac surgery. Future investigation should seek to evaluate the utility of screening programs for affective disorders in those individuals who develop delirium in the postoperative period.

Effect of post-discharge virtual wards on improving outcomes in heart failure and non-heart failure populations: A systematic review and meta-analysis.

BACKGROUND: Unplanned hospital admissions in high-risk patients are common and costly in an increasingly frail chronic disease population. Virtual Wards (VW) are an emerging concept to improve outcomes in these patients. PURPOSE: To evaluate the effect of post-discharge VWs, as an alternative to usual community based care, on hospital readmissions and mortality among heart failure and non-heart failure populations. DATA SOURCES: Ovid MEDLINE, EMBASE, PubMed, the Cochrane Database of Systematic Reviews, SCOPUS and CINAHL, from inception through to Jan 31, 2017; unpublished data, prior systematic reviews; reference lists. STUDY SELECTION: Randomized trials of post-discharge VW versus community based, usual care that reported all-cause hospital readmission and mortality outcomes. DATA EXTRACTION: Data were reviewed for inclusion and independently extracted by two reviewers. Risk of bias was assessed using the Cochrane Collaboration risk of bias tool. DATA SYNTHESIS: In patients with heart failure, a post-discharge VW reduced risk of mortality (six trials, n = 1634; RR 0.59, 95% CI = 0.44-0.78). Heart failure related readmissions were reduced (RR 0.61, 95% CI = 0.49-0.76), although all-cause readmission was not. In contrast, a post-discharge VW did not reduce death or hospital readmissions for patients with undifferentiated high-risk chronic diseases (four trials, n = .3186). LIMITATIONS: Heterogeneity with respect to intervention and comparator, lacking consistent descriptions and utilization of standardized nomenclature for VW. Some trials had methodologic shortcomings and relatively small study populations. CONCLUSIONS: A post-discharge VW can provide added benefits to usual community based care to reduce all-cause mortality and heart failure-related hospital admissions among patients with heart failure. Further research is needed to evaluate the utility of VWs in other chronic disease settings.

Anaplasmosis: An emerging tick-borne disease of importance in Canada.

Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Anaplasma phagocytophilum. As a tick-borne disease, the public health impact of HGA continues to increase with range expansion of the disease vector. The clinical presentation of HGA is often a non-specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an appropriate diagnosis. Herein we present three cases of HGA, highlighting the spectrum of disease by which HGA can manifest. Although each case has their unique features, we outline important shared clinical elements to facilitate an empiric diagnosis while definitive laboratory investigations are pending. Our case series further serves to highlight the critical importance of prompt antimicrobial treatment to reduce morbidity and potential mortality.