Exploring the potential harm of varied blood storage on patients undergoing cardiovascular surgery.

BACKGROUND AND OBJECTIVES: Debate exists surrounding the optimal duration of red blood cell (RBC) storage. A hypothesis emerging from previous research suggests that exposure to fresh blood may be harmful to patients undergoing cardiac surgery. This study uses a large transfusion medicine database to explore the association between in-hospital mortality and red cell storage duration. MATERIALS AND METHODS: This is an exploratory retrospective cohort study of all adult patients at Hamilton, Canada, over a 14-year period that received at least one allogeneic red cell transfusion during their hospitalization for cardiac surgery requiring bypass. The primary outcome for the study was in-hospital death. Analysis was performed using multivariate Cox regression modelling with time-dependent and time-independent covariates and stratification variables. Five models with varying definitions for short, intermediate and prolonged duration of RBC storage were tested. RESULTS: From March 2004 to December 2017, 11,205 patients met the inclusion criteria and were included in the regression analyses. No significant effect of short-duration red storage on patient mortality was observed in all statistical models, with the red cells stored for the longest duration as the reference group. When patients who received exclusively fresh (hazard ratio [HR] 1.040, 95% confidence interval [CI] 0.588-1.841, p-value = 0.893) and older aged (HR 1.038, 95% CI 0.769-1.1.402, p-value = 0.0801) RBCs were compared with those who received exclusively mid-age red cells as the reference, statistical significance was similarly not reached. CONCLUSION: Red cells stored for the shortest duration are not associated with increased risk of mortality among cardiac surgery patients.

An evaluation of the clinical impacts of 7-day platelets.

BACKGROUND: In August 2017, Canadian Blood Services extended the shelf-life of platelet concentrates from 5 to 7 days. The clinical impacts of this policy change remain unclear. STUDY DESIGN AND METHODS: We used a before-after retrospective design of platelet-transfused adult inpatients in Hamilton, ON, Canada. Data were captured for 18 months before (Period 1: February 2016-July 2017) and 18 months after (Period 2: September 2017-February 2019) 7-day platelet implementation. Primary outcome was absolute platelet count increment (ACI) in univariate and multivariate analyses adjusted for confounders. Data were obtained from our institution's transfusion database, Ontario's Transfusion Transmitted Injuries Surveillance System, and the blood supplier. RESULTS: Overall, 1360 patients with single dose platelet transfusions were included in Period 1 and 1211 patients in Period 2. Median age at admission was 66 years, and approximately 40% of patients underwent cardiac surgery. Using a non-inferiority margin of -10 × 109 /L, platelets transfused during the 7-day storage period were non-inferior to those transfused in the 5-day storage period [mean count difference - 4.63 × 109 /L (95% CI -7.40 to -1.87, p = 0.0001)]. However, platelet ACIs following transfusion consistently trended lower in the 7-day group for all patients and subgroups. No differences in secondary clinical outcomes were observed. Platelet expiry reduced from 8.1 to 6.3% (p < 0.0001). CONCLUSION: Platelet transfusions following 7-day storage policy were non-inferior to transfusions in the 5-day policy period, although reduced ACIs were observed. There were no increases in adverse clinical outcomes.

KEL1 negative red cell transfusions for females of current or future child-bearing potential: A clinical impact and feasibility study.

BACKGROUND: Anti-K is an alloantibody stimulated in response to the KEL1 antigen and may cause hemolytic disease of the fetus and newborn (HDFN). Provision of KEL1 negative blood to females of child-bearing potential was not our practice. We assessed the impact of our policy and assessed feasibility of a KEL1 negative transfusion policy. STUDY DESIGN AND METHODS: This is a cohort study spanning Jan 1, 2007-Jun 30, 2017 in Hamilton, Canada. Data were obtained via our institution's transfusion database. Chart reviews of females age ≤45 with anti-K were performed; data on RBC KEL1 phenotype were obtained from the blood supplier when needed to ascertain the cause of alloimmunization. Descriptive analysis of hospital KEL1 negative inventory demand and supply was performed. RESULTS: From Jan 2007-Jun 2017, 8.6% of all RBC units transfused were provided to females age ≤45. There were 111 females with detectable anti-K. Median age at time of antibody detection was 34 years (interquartile range 27-40) and 28 of 111 (25.2%) patients may have been alloimmunized by transfusion. Of 49 pregnancies, seven had complications due to anti-K. We estimated that our existing RBC inventory (with 16% units known to be KEL1 negative in 2017) is sufficient to meet demand and support a KEL1 negative transfusion policy for females age ≤45. CONCLUSION: Transfusion was responsible for alloimmunization in 25% of females with anti-K over 10 years. Analysis of supply and demand can be used to inform feasibility of a KEL1 negative transfusion policy.

Accuracy of International Classification of Diseases, 10th Revision Codes for Identifying Sepsis: A Systematic Review and Meta-Analysis.

Administrative databases are increasingly used in research studies to capture clinical outcomes such as sepsis. This systematic review and meta-analysis examines the accuracy of International Classification of Diseases, 10th revision (ICD-10), codes for identifying sepsis in adult and pediatric patients. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science, CENTRAL, Epistemonikos, and McMaster Superfilters from inception to September 7, 2021. STUDY SELECTION: We included studies that validated the accuracy of sepsis ICD-10 codes against any reference standard. DATA EXTRACTION: Three authors, working in duplicate, independently extracted data. We conducted meta-analysis using a random effects model to pool sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We evaluated individual study risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool and assessed certainty in pooled diagnostic effect measures using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS: Thirteen eligible studies were included in the qualitative synthesis and the meta-analysis. Eleven studies used manual chart review as the reference standard, and four studies used registry databases. Only one study evaluated pediatric patients exclusively. Compared with the reference standard of detailed chart review and/or registry databases, the pooled sensitivity for sepsis ICD-10 codes was 35% (95% CI, 22-48, low certainty), whereas the pooled specificity was 98% (95% CI: 98-99, low certainty). The PPV for ICD-10 codes ranged from 9.8% to 100% (median, 72.0%; interquartile range [IQR], 50.0-84.7%). NPV ranged from 54.7% to 99.1% (median, 95.9%; interquartile range, 85.5-98.3%). CONCLUSIONS: Sepsis is undercoded in administrative databases. Future research is needed to explore if greater consistency in ICD-10 code definitions and enhanced quality measures for ICD-10 coders can improve the coding accuracy of sepsis in large databases.

Symmetrical peripheral gangrene in critical illness.

Symmetrical peripheral gangrene (SPG) is a disabling complication that affects a small proportion of patients who survive critical illness. Its pathogenesis reflects profoundly disturbed procoagulant-anticoagulant balance in susceptible tissue beds secondary to circulatory shock (cardiogenic, septic). There is a characteristic SPG triad: (a) shock (hypotension, lactic acidemia, normoblastemia, multiple organ dysfunction), (b) disseminated intravascular coagulation (DIC), and (c) natural anticoagulant depletion (protein C, antithrombin). In recent years, risk factors for natural anticoagulant depletion have been identified, most notably acute ischemic hepatitis ("shock liver"), which is seen in at least 90% of patients who develop SPG. Moreover, there is a characteristic time interval (2-5 days, median 3 days) between the onset of shock/shock liver and the beginning of ischemic injury secondary to peripheral microthrombosis ("limb ischemia with pulses"), reflecting the time required to develop severe depletion in hepatically-synthesized natural anticoagulants. Other risk factors for natural anticoagulant depletion include chronic liver disease (e.g., cirrhosis) and, possibly, transfusion of colloids (albumin, high-dose immunoglobulin) lacking coagulation factors. A causal role for vasopressor therapy is unproven and is unlikely; this is because critically ill patients who develop SPG do so usually after at least 36-48 hours of vasopressor therapy, implicating a time-dependent pathophysiological mechanism. The most plausible explanation is a progressive time-dependent decline in key natural anticoagulant factors, reflecting ongoing DIC ("consumption"), proximate liver disease whether acute or chronic ("impaired production"), and colloid administration ("hemodilution"). Given these evolving concepts of pathogenesis, a rationale approach to prevention/treatment of SPG can be developed.

Circulating heparin-like anticoagulants: Case report and review of literature.

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Management of iron deficiency.

Iron deficiency (ID) affects billions of people worldwide and remains the leading cause of anemia with significant negative impacts on health. Our approach to ID and iron deficiency anemia (IDA) involves three steps (I3): (1) identification of ID/IDA, (2) investigation of and management of the underlying etiology of ID, and (3) iron repletion. Iron repletion options include oral and intravenous (IV) iron formulations. Oral iron remains a therapeutic option for the treatment of ID in stable patients, but there are many populations for whom IV iron is more effective. Therefore, IV iron should be considered when there are no contraindications, when poor response to oral iron is anticipated, when rapid hematologic responses are desired, and/or when there is availability of and accessibility to the product. Judicious use of red cell blood transfusion is recommended and should be considered only for severe, symptomatic IDA with hemodynamic instability. Identification and management of ID and IDA is a central pillar in patient blood management.

Premedication for the prevention of nonhemolytic transfusion reactions: a systematic review and meta-analysis.

BACKGROUND: The efficacy of premedication for the prevention of nonhemolytic transfusion reactions remains controversial. This systematic review and meta-analysis assessed the effect of premedication on the rate of nonhemolytic transfusion reactions after allogeneic blood transfusion. STUDY DESIGN AND METHODS: We searched the literature using CENTRAL, MEDLINE, EMBASE, ISI Web of Science, and clinicaltrials.gov databases from inception until October 31, 2018. We included all randomized controlled trials comparing premedication to placebo or no treatment in patients receiving any labile blood product. Outcome measures were reported as relative risks (RRs) with 95% confidence intervals (CIs). Data were combined for similar outcomes where appropriate using a random-effects model. Analyses were done at both the patient and transfusion level. RESULTS: Three randomized trials using acetaminophen and antihistamine as premedication met the inclusion criteria. A total of 517 patients received 4444 red blood cell or platelet transfusions. Pooled patient-level estimates with premedication for all nonhemolytic, febrile nonhemolytic, and minor allergic reactions were RR, 0.92 (95% CI, 0.63-1.35); RR, 0.54 (95% CI, 0.26-1.1); and RR, 1.37 (95% CI 0.81-2.31), respectively. Transfusion-level analyses also showed no benefit with premedication. Of 517 patients randomized, only 27 (5.2%) had a history of transfusion reactions. CONCLUSION: Routine premedication with acetaminophen and antihistamines did not prevent nonhemolytic transfusion reactions; however, the estimate of effect was greatest for febrile reactions. The impact of premedication in patients with a prior history of transfusion reactions remains unknown and requires further evaluation in future clinical trials.

The association between platelet transfusions and mortality in patients with critical illness.

BACKGROUND: Platelet (PLT) transfusions are frequently administered in the setting of critical illness but their clinical impacts remain unknown. This study examined the association between PLT transfusions and death in a large intensive care unit (ICU) patient population. STUDY DESIGN AND METHODS: Using a transfusion registry spanning 2008 to 2015, this study assessed effect of in-ICU PLT transfusions on ICU and in-hospital mortality using a stratified, time-dependent Cox proportional hazards model adjusted for illness severity, thrombocytopenia, and other confounders. Patients with known malignancy were excluded. Exposure to PLT transfusions were analyzed dichotomously (ever or never transfused) and continuously (number of transfusions). Medical, general surgery, and cardiac surgery subgroups were analyzed separately. RESULTS: Overall 32,842 adult patients were admitted to ICU, and 4927 patients received PLT transfusion(s). Crude in-ICU and in-hospital mortality were higher for PLT-transfused patients compared to nontransfused patients (9.2% vs. 6.7% and 12.3% vs. 9.3%, respectively). After confounders were adjusted for, PLT transfusions (ever vs. never) were not associated with increased mortality in ICU (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.60-1.02; p = 0.06) or in hospital (HR, 0.89; 95% CI, 0.68-1.09; p = 0.41). Continuous exposure analysis also showed no association between PLT transfusions and death. PLT transfusions have a protective effect on in-hospital mortality in the subgroup of general surgery patients (HR, 0.71; 95% CI, 0.51-0.99; p = 0.04; ever or never analysis). CONCLUSION: Platelet transfusions were not associated with increased risk of death in critically ill patients. Further studies are required to identify subgroups for which PLT transfusions may be beneficial.

Transfusion Safety: The Nature and Outcomes of Errors in Patient Registration.

The transfusion chain is susceptible to error at every step. Accurate patient registration is a key first step that links a patient with their historical medical profile, yet patient registration is marked by its own challenges. Registration errors are deviations from standard operating procedures that occur during the process of patient registration. A frequent consequence of registration errors is the obfuscation of historical information and patient misidentification. Through duplicate registrations, patient information can be spread across multiple records and through hybrid registrations information from multiple patients can be combined into a single record. Patients with the same core identifiers, and the misuse of health insurance information also pose a threat to accurate registration. In the context of transfusion, this can lead to ABO discrepancies, failing to match for previously identified alloantibodies, and redundant serological investigations. Other consequences include missed billing opportunities and the inadvertent sharing of medical information. Reducing the occurrence of registration errors can be achieved through a multifaceted approach combining targeted educational efforts with technological improvements to the registration system. A recent development being the use of biometric identifiers. Despite their frequency, published reports on the occurrence and underlying cause of registration errors are rare. Most reports are found within articles on general medical errors or misidentification events and consequently, the true rate of registration errors among health information systems is not known. Here we summarize literature pertaining to how and why registration errors occur and their implications in the context of blood transfusion.

Red blood cells, still vital after all these years: Commentary on Canadian Blood Services' International Symposium 2017.

Canadian Blood Services (CBS), Canada's national blood transfusion service, has for many years sponsored an annual conference, for the education and awareness of interested participants, showcasing the latest evidence-based understanding of both basic science and clinical issues in transfusion medicine and science. The 15th iteration of this symposium took place September 9, 2017 and focused on some of the vital aspects of red blood cells (RBC), in line with the" 3Rs" concept, namely the provision of the Right red blood cell (RBC) product to the Right patient at the Right time. Presentations touched upon: the evolution of blood banking in North America; the monocyte monolayer assay as a predictor of post-transfusion hemolysis; hemoglobin-based oxygen carriers; RBC alloimmunization; serological approaches to complex RBC antibody problems; randomized clinical trials related to the age of stored RBC; RBC genotyping; pathophysiology, prevention and treatment of hemolytic disease of the fetus and newborn (HDFN); and testing and timing in perinatal serology. This commentary provides summaries of all speakers' presentations annotated with relevant references. Special thanks are due to all contributors for their praiseworthy approaches in sharing their experiences and knowledge on this interesting scientific/clinical and management theme.

Exploring donor and product factors and their impact on red cell post-transfusion outcomes.

The impact of donor characteristics, red cell age, and red cell processing methods on recipient outcomes is an emerging area of research. Knowledge generated from exploring this transfusion continuum has the potential to change the way donors are selected and how donations are processed and stored with important clinical and operational impact. Recently, donor characteristics including age, gender, donation frequency, genetics, and ethnicity have been shown to affect product quality and possibly recipient outcomes. The structural, biochemical and immunological changes that occur with red cell storage appear to not cause harm to blood recipients after 14 randomized clinical trials. However, both in vitro and clinical data are now beginning to question the safety of blood stored for a shorter duration. Whole blood filtration, a method of blood processing, has been linked to inferior recipient outcomes when compared to red cell filtration. Collectively, this emerging body of literature suggests that pre-transfusion parameters impact product quality and recipient outcomes and that no 2 units of red cells are quite the same. This review will summarize both the pre-clinical and clinical studies evaluating these associations.

Platelet Transfusion Practices in the ICU: Data From a Large Transfusion Registry.

BACKGROUND: Platelet transfusions are commonly used in critically ill patients, but transfusion thresholds, count increments, and predictors of ineffectual transfusions remain unclear. METHODS: This retrospective study included consecutive adult nononcology patients who received platelet transfusions in ICUs at three Canadian academic hospitals between 2006 and 2015. Data were collected from a validated transfusion database. We determined independent predictors of ineffectual platelet transfusions, defined as transfusions that raised platelet counts by < 5 × 10(9)/L. Reasons for transfusion were adjudicated in a subgroup of patients who underwent transfusion despite normal platelet counts. RESULTS: We identified 7,320 ICU admissions (n = 7,073 patients) during which 15,879 platelet transfusions were administered. Most admissions (78.7%) were for cardiac surgery. Based on 5,700 analyzable transfusions, the median pretransfusion platelet count was 87 × 10(9)/L (interquartile range [IQR], 57-130). The pretransfusion platelet count was ≥ 50 × 10(9)/L and ≥ 150 × 10(9)/L for 79.6% and 17.8% of transfusions, respectively. Reasons for transfusion despite a normal platelet count were active bleeding or surgery in patients receiving antiplatelet agents or anticoagulants. The median platelet count increment was 23 × 10(9)/L (IQR, 7-44), and 21.8% of transfusions were ineffectual. ABO incompatibility, sepsis, liver disease, and red cell and cryoprecipitate transfusions were associated with a poor platelet count increment. CONCLUSIONS: Platelet transfusions were commonly used in the ICU when platelet counts were ≥ 50 × 10(9)/L. One platelet transfusion increased platelet count by 23 × 10(9)/L. One in five transfusions was ineffectual, and ABO incompatibility was identified as a modifiable risk factor. These data can help direct efforts to reduce platelet overuse and improve transfusion quality.

Hemophagocytic Lymphohistiocytic Syndrome and Enteropathy-Associated T-cell Lymphoma in a Patient with Refractory Celiac Disease.

A 70-year-old woman with celiac disease presented with weight loss and diarrhea unresponsive to gluten-free diet (GFD) and prednisone. Diagnosis of type 2 refractory celiac disease (RCD) was made by small intestinal biopsies showing severe villous blunting and intraepithelial lymphocytosis. She was diagnosed with hemophagocytic lymphohistiocytic syndrome (HLH) after developing fever, pancytopenia, hypofibrinogenemia, elevated ferritin, and demonstration of hemophagocytosis on her bone marrow biopsy. An expert pathologist on lymphoma reviewed her biopsies and revised the final diagnosis to type 1 enteropathy-associated T-cell lymphoma (EATL) based on large T-cells infiltrating the lamina propria. We describe the first case of HLH associated with localized EATL and RCD.