Are outcomes of locally advanced cervical cancer associated with prebrachytherapy hemoglobin values and transfusion practice? An observational study comparing two large academic centres with divergent clinical guidelines.

BACKGROUND AND PURPOSE: Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L. MATERIALS AND METHODS: This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2). RESULTS: Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality. CONCLUSIONS: The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use.

International Survey of the Management of Disseminated Intravascular Coagulation Among Pediatric and Neonatal Health Care Practitioners.

The International Society of Thrombosis and Hemostasis (ISTH) provides objective disseminated intravascular coagulation (DIC) measurement through diagnostic criteria validated in adults. The applicability of these criteria in pediatric and neonatal DIC is controversial and unvalidated. Primary objective: to evaluate current practice in pediatric and neonatal DIC management among different specialties. Secondary objective: to understand the potential impact of developmental hemostasis on DIC laboratory evaluation. We performed a multicenter survey between January and September 2016. The questionnaire was distributed internationally through professional societies. In all, 211 responses were received, of which 160 were full responses and 51 were partial. Overall, 85% of respondents practiced in tertiary academic centers; 70% practiced in pediatric-only hospitals. The majority of respondents (42%) used their personal clinical experience in the management of DIC. Sixty percent of respondents treated DIC until the resolution of both clinical and laboratory parameters. Laboratory investigations were monitored in the majority of DIC cases without thrombosis or bleeding (80%); age-specific reference ranges for tests were lacking in 20% of pediatric-only hospitals and 35% of combined pediatric/adult hospitals. Adherence to standardized DIC guidelines was poor but varied by geographical location. This survey reveals variable practices among pediatricians in the management of DIC. Further studies are needed to validate the DIC diagnostic criteria in children.

Understanding the nursing practices and perspectives of transfusion reaction reporting.

AIMS AND OBJECTIVES: The aim of this study was to investigate nurse perspectives on transfusion-related adverse reaction reporting practices. BACKGROUND: Transfusion-related adverse reaction reporting is an essential component of hemovigilance in Canada, but reporting rates vary and under-reporting of minor transfusion-related adverse reactions exists. To our knowledge, this is the first report of nursing transfusion-related adverse reaction reporting attitudes. DESIGN: This qualitative descriptive study explored the nursing practices and perspectives of transfusion-related adverse reaction reporting by conducting one-on-one interviews with nurses (n = 25) working in adult oncology inpatient and outpatient units. METHODS: Data were thematically analysed; data collection ended when saturation was reached. The COREQ checklist was used to guide this study. RESULTS: The study revealed that the nursing practices of transfusion-related adverse reaction reporting are not standardised to meet the institutional reporting guidelines. Under-reporting of febrile reactions exists at this institution. Major concepts uncovered included the factors impacting nurses' transfusion-related reporting practices, as well as barriers and facilitators to transfusion reporting. CONCLUSION: A practice change in transfusion-related adverse reaction reporting is needed to achieve optimal hemovigilance at this institution. Using the barriers and facilitators identified in this study, institutions can better inform future interventions by employing strategies like TR reporting education in order to improve reporting of transfusion-related adverse reactions in this hospital and other similar institutions. RELEVANCE TO CLINICAL PRACTICE: This study informs clinical practice and decision-making for nurses and nursing educators who manage blood transfusion administration procedures.

When donor T cells attack: The curious case of liver transplant-associated acute graft-versus-host-disease.

Graft versus host disease is a rare but deadly complication of solid organ transplant. Clinical features of graft-versus-host-disease are non-specific, which may lead to delayed diagnosis as more common conditions including infections or drug reactions are considered. We describe a 54-year-old male patient who underwent liver transplantation for alcohol use disorder-related cirrhosis and developed acute graft-versus-host disease. Initial clinical presentation included dermatitis, bone marrow failure and enteritis. Results of skin biopsy and cytogenetic studies were consistent with liver transplant-associated acute graft-versus-host disease. The importance of this case is to highlight to transplant physicians and surgeons the challenges of diagnosing graft-versus-host-disease. In our case, pre-existing partnerships among the liver and hematopoietic stem cell transplant teams, transfusion medicine specialists, critical care specialists and facilitated timely communication relevant to confirming graft-versus-host disease. We propose an algorithm to assist in the workup of suspected graft-versus-host disease. Because this condition is characterized by high mortality, a high index of suspicion is imperative for prompt diagnosis and optimal management of the donor-recipient immune interaction when patients present with classic clinical features.

The impact of red blood cell transfusion on mortality and treatment efficacy in patients treated with radiation: A systematic review.

INTRODUCTION: Packed red blood cell (RBC) transfusion is frequently used in patients undergoing radiotherapy (RT) because retrospective data suggest that anemic patients may respond sub-optimally to RT. No high-quality evidence currently exists to guide transfusion practices and establish hemoglobin (Hb) transfusion thresholds for this patient population, and practice varies significantly across centers. This systematic review investigated whether maintaining higher Hb via transfusion in radiation oncology patients leads to improved outcomes. METHODS: We performed a literature search of studies comparing RBC transfusion thresholds in radiation oncology patients. Included studies assessed patients receiving RT for malignancy of any diagnosis or stage. Excluded studies did not evaluate Hb or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional control, number of transfusions and adverse events. RESULTS: One study met inclusion criteria. The study pooled results from two randomized controlled trials that stratified anemic patients with head and neck squamous cell carcinoma to RBC transfusion versus no transfusion. The study found no significant differences in overall survival or locoregional control after five years, despite increased Hb levels in the transfused group. We conducted a narrative review by extracting data from 10 non-comparative studies involving transfusion in patients receiving RT. Results demonstrated no consistent conclusions regarding whether transfusions improve or worsen outcomes. CONCLUSIONS: There is a lack of data on the effects of RBC transfusion on outcomes in patients undergoing RT. Well-designed prospective studies are needed in this area.

Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis.

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.

Underlying disorders of disseminated intravascular coagulation: Communication from the ISTH SSC Subcommittees on Disseminated Intravascular Coagulation and Perioperative and Critical Care Thrombosis and Hemostasis.

BACKGROUND: Disseminated intravascular coagulation (DIC), a systemic activation of coagulation, presents with multiple clinical and laboratory manifestations. In this International Society on Thrombosis and Haemostasis (ISTH) communication, we examined the importance of identifying the underlying disorder causing DIC to help physicians in the diagnosis and management of this common and severe condition. METHODS: Eight DIC experts participated in a three-step consensus process that searched for published guidelines and diagnostic scores on DIC to create a preliminary list of DIC underlying disorders from those reported in the literature Overall, 13 papers were identified, including three guidelines, one harmonization paper by the ISTH, one ISTH recommendation paper on cancer-associated DIC, five general diagnostic scores, two scores specific for pregnancy, and one specific for children. We then assessed the strength of the evidence on the association between the disease and DIC as many postulated DIC-associated disorders are rare. KEY RESULTS: Eight main subgroups - 'severe infection', 'solid tumour', 'haematological neoplasia', 'pregnancy complication', 'vascular disease', 'newborn-complication', 'tissue damage due to internal or external insult', and 'chemical and biological agent' - and a detailed list of specific causes of DIC were provided. CONCLUSIONS & INFERENCES: Our results suggest more data are needed to determine the association between DIC and specific diseases such as malignant lymphoma, colorectal cancer, or vasculitis, for which the evidence remains limited. When a patient develops a coagulopathy consistent with DIC, the first step is to immediately search for an underlying disorder, including specific causes that are rarely associated with DIC and to consider that patients may have more than one cause of DIC to identify the principal precipitating disorder to prioritize treatment.

The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis.

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain. OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients. METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials. RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction  = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1). CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

Intersecting Worlds of Transfusion and Transplantation Medicine: An International Symposium Organized by the Canadian Blood Services Centre for Innovation.

The principal theme of the symposium was centered on how the world of regenerative medicine intersects with that of transfusion medicine, with a particular focus on hematopoietic stem cells (HSCs) and stem cell therapies. The symposium highlighted several exciting developments and identified areas where additional research is needed. A revised map of human hematopoietic hierarchy was presented based on the functional and phenotypic analysis of thousands of single stem and progenitor cells from adult bone marrow and fetal liver. These analyses revealed that multipotency is largely restricted to the HSC and multipotent progenitor compartments in adult bone marrow where most progenitors are unipotent, whereas fetal liver contains a large number of distinct oligopotent progenitors. Furthermore, unlike adult bone marrow, multipotency is extended in the downstream progenitors in the hierarchy in the fetal liver stage. Production of platelets ex vivo from HSCs is emerging as a potentially viable option because of advances in culture techniques that combine cytokine mixtures, small molecules, and shear stress. However, limited HSC expansion and low platelet yield from culture-derived megakaryocytes remain problematic. Evidence was presented to support stricter guidelines for transfusion of platelets and red blood cells practices in allogeneic HSC transplant patients, although evidence is often extrapolated from general indications. Basic principles of human leukocyte antigen testing in HSC transplant were described, emphasizing the need for a national (and global) stem cell donor registry. Ongoing research is aimed at improving cellular cryopreservation including the establishment of a new thawing protocol that improves viability of umbilical cord blood CD34+ cells. Umbilical cord blood transplantation practices have also been improved; recent studies suggest noninferior outcomes when patients are transplanted with umbilical cord blood vs a matched adult donor. Finally, mesenchymal stem cell infusion is an example of a cellular therapy useful for immunomodulation. Preclinical trials suggest that mesenchymal stem cells may be effective in managing sepsis. In conclusion, practices and research surrounding HSCs are continuing to evolve rapidly as new information is obtained.

Transfusion premedication practices among pediatric health care practitioners in Canada: results of a national survey.

BACKGROUND: Although not supported by strong evidence, premedication (pretransfusion medication) is commonly prescribed to patients who have had a transfusion reaction. The research questions were: 1) What are Canadian pediatric practitioners' views and practices regarding premedication and 2) what are barriers to reducing premedication overuse in pediatrics? STUDY DESIGN AND METHODS: An online survey targeted hematology/oncology, emergency medicine, general surgery, intensive care, and cardiac intensive care practitioners in all 16 Canadian pediatric tertiary hospitals. The survey included four sections: demographic, clinical, future directions, and organizational questions. RESULTS: Fifty-five individuals from 15 of 16 pediatric tertiary care sites completed the survey: 53 physicians and two nurse practitioners. More than half of the respondents (55%; 30/55) were pediatric hematology/oncology providers, and 35% (19/55) were directors of their respective divisions. Eighty-seven percent of respondents estimated that they premedicate up to 25% of red blood cell (RBC) transfusions, and 13% premedicate 26% to 50% RBC transfusions. Proportions were similar for platelet transfusions. Most respondents reported that trainees are involved in transfusion and premedication order decisions. Seven percent believe that their hospital does not use leukoreduction and 27% are not sure. Sixty-five percent of respondents were not aware of a clinical practice guideline or a standard order set (SOS) at their institution: 51% are interested in having both available. Factors influencing the decision to premedicate and barriers to change were identified. CONCLUSION: Premedication practices are variable in Canadian pediatric academic hospitals. Evidence-based premedication clinical practice guidelines and SOS could be explored as a way to standardize practices. There were perceived educational and institutional barriers to practice change.

Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol.

INTRODUCTION: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. METHODS AND ANALYSIS: First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. ETHICS AND DISSEMINATION: Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013003526.

Neurological PRESentations in Sickle Cell Patients Are Not Always Stroke: A Review of Posterior Reversible Encephalopathy Syndrome in Sickle Cell Disease.

Acute neurological changes in sickle cell disease (SCD) patients often raise the suspicion for stroke. Posterior reversible encephalopathy syndrome (PRES) can mimic stroke in its clinical presentation. We aimed to (i) review the PRES literature in SCD patients including clinical presentation, risk factors, pathophysiology, and management and (ii) elucidate the distinction between PRES and stroke in SCD. The exact pathophysiology of PRES in SCD remains elusive but is likely multifactorial and related to sickling, ischemia, and chronic anemia predisposing to vasogenic edema. PRES and stroke in SCD are distinguishable conditions. Our review may help elucidate a clinical approach to this distinction.

Practising what we preach: A look at healthy active living policy and practice in Canadian paediatric hospitals.

BACKGROUND: In the past 30 years, the rate of obesity has risen considerably among Canadian children. Paediatric hospitals are in a unique position to model healthy environments to Canadian children. OBJECTIVE: To obtain an overview of healthy active living (HAL) policy and practice in Canadian paediatric hospitals. METHODS: Working in partnership with the local Canadian Paediatric Society HAL champions and the Canadian Association of Paediatric Health Centres liaisons, a nationwide survey was conducted in 2006/2007 to identify healthy eating, physical activity and smoking cessation practices in all 16 Canadian paediatric academic hospitals. RESULTS: Policies addressing healthy eating and/or physical activity promotion were present in 50% of hospitals with a greater focus on nutrition. Wellness committees were created in 50% of the hospitals, most of which were recently established. Healthy food options were available in cafeterias, although they were often more expensive. Fast food outlets were present in 75% of hospitals. Although inpatient meals were designed by dietitians, 50% offered less nutritious replacement kids meals (ie, meal substitutions) on request. Options for play available to inpatients and outpatients were primarily sedentary, with screen-based activities and crafts predominating over active play. Physical activity promotion for staff focused on reduced membership fees to fitness centres and classes. CONCLUSION: Canadian paediatric hospitals do not adequately promote HAL for patients and staff. The present study findings suggest further effort is required to create necessary healthy lifestyle modifications in these institutions through Canadian Paediatric Society/Canadian Association of Paediatric Health Centres-led policy development and implementation initiatives. A national-level policy framework is required to regulate interhospital variability in policies and practices.