Publications by authors named "Yulia Lin"

107 Publications

Examining prescribing practices with respect to oral iron supplementation for post-partum anemia: a retrospective review.

J Matern Fetal Neonatal Med 2021 Nov 29:1-7. Epub 2021 Nov 29.

Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Canada.

Purpose: Treatment for post-partum anemia frequently entails oral iron supplementation, but questions remain regarding optimal dosing, frequency, and efficacy. The objective of this study was to describe oral iron prescribing practices in post-partum women delivered Cesarean section, and identify factors associated with iron supplementation.

Methods: A retrospective review of Cesarean section deliveries at a single tertiary center between May 2019 and April 2020 was undertaken. Patient demographics, hematological indices, indication for Cesarean section and discharge prescriptions were collected. Univariate and multivariable analyses were performed to identify factors associated with oral iron prescription at discharge.

Results: During the study period, 1470 women were eligible for inclusion. The mean age at delivery was 34.4 ± 4.9 years and mean gestational age was 37.2 ± 3.6 weeks. Most pregnancies (92%) were singleton. Ninety-six total patients (6.5%) received intravenous iron post-partum. Fourteen percent of women (210/1470) received prescriptions for oral iron at discharge, most commonly ferrous fumarate (61.9%, 130/210). The most common dose provided was 300 mg (145/210). Ante-partum ferritin was available for most patients (64.3%, 945/1470), but only for 17 post-partum patients (1.2%). Factors significantly associated with oral iron prescription were earlier gestational age at birth (aOR 0.93, 95% CI 0.89-0.97), history of complications during pregnancy or labor (aOR 1.92, 95% CI 1.26-2.98), higher blood loss (aOR 2.66, 95% CI 1.36-5.44), post-partum anemia (aOR 6.28, 95%-CI 4.41-8.96), blood transfusion (aOR 5.43, 95%-CI 1.81-18.19) and antenatal iron supplementation (aOR 5.70, 95%-CI 4.02-8.17).

Conclusions: In summary, a relatively small proportion of women following Cesarean section were prescribed oral iron at discharge. We identified several factors associated with post-partum iron supplementation. This information will inform future prospective studies investigating the efficacy of iron supplementation in the treatment of post-partum anemia.
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http://dx.doi.org/10.1080/14767058.2021.2008897DOI Listing
November 2021

Cost-effectiveness of eltrombopag versus intravenous immunoglobulin for the perioperative management of immune thrombocytopenia.

Blood Adv 2021 Nov 15. Epub 2021 Nov 15.

McMaster University, Hamilton, Canada.

Eltrombopag has been shown to be non-inferior to intravenous immunoglobulin (IVIG) for improving perioperative platelet counts in patients with immune thrombocytopenia (ITP) in a randomized trial; thus, cost is an important factor for treatment and policy decisions. We used patient-level data from the trial to conduct a cost-effectiveness analysis comparing perioperative eltrombopag 50mg daily starting dose, with IVIG 1 or 2g/kg (according to local practice) from a Canadian public healthcare payer's perspective over the observation period, from preoperative day 21 to postoperative day 28. Resource utilization data were obtained from the trial data (eltrombopag, n=38; IVIG, n=36) and unit costs were collected from the Ontario Schedule of Benefits, Ontario Drug Formulary, and secondary sources. All costs were adjusted to 2020 Canadian dollars. We calculated the incremental cost per patient for all patients randomized. Uncertainty was addressed using non-parametric bootstrapping. The use of perioperative eltrombopag for patients with ITP resulted in a cost-saving of $413 Canadian dollars per patient. Compared with IVIG, the probability of eltrombopag being cost-effective was 70% even with zero willingness to pay. In a sensitivity analysis based on IVIG dose, we found that with the higher dose of IVIG (2g/kg), eltrombopag saved $2,714 per patient; whereas with the lower dose of IVIG (1g/kg), eltrombopag had a higher mean cost of $562 per patient. In summary, based on data from the randomized trial that demonstrated non-inferiority, the use of eltrombopag for the management of ITP in the perioperative setting was less costly than IVIG.
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http://dx.doi.org/10.1182/bloodadvances.2021005627DOI Listing
November 2021

Safety of idarucizumab in the reversal of dabigatran at six tertiary care Ontario hospitals.

Res Pract Thromb Haemost 2021 Jul 7;5(5):e12535. Epub 2021 Aug 7.

Departments of Laboratory Medicine and Pathobiology & Department of Medicine University of Toronto Toronto ON Canada.

Background: Idarucizumab, a monoclonal antibody fragment that reverses the anticoagulant effect of dabigatran, was approved for use in Canada in 2016.

Objective: Our objective was to assess the safety of idarucizumab among patients who received the drug within the first 3 years of its use in Canada.

Patients/methods: We performed a retrospective health records review of all idarucizumab use, excluding use in those <18 years of age, between May 16, 2016, and August 1, 2019, at six Ontario tertiary care hospitals. The primary outcome was mortality. The secondary outcomes were in-hospital arterial thrombotic event (ATE), in-hospital venous thromboembolism (VTE), length of hospital stay, and length of critical care stay.

Results: A total of 85 patients received idarucizumab during the study period for the following indications: 37 (43.5%) for spontaneous bleeding, 28 (32.9%) for traumatic bleeding, 11 (12.9%) for emergency surgeries/procedures, 5 (5.9%) for elective surgeries/procedures, and 4 (4.7%) for other indications. Nineteen patients (22.4%; 95% confidence interval [CI], 14.8%-32.3%) did not survive their hospitalization. During hospitalization, two patients (2.4%; 95% CI, 0.7%-8.2%) had ATE, and three patients (3.5%; 95% CI, 1.2%-9.9%) had VTE. The median length of stay was 8 (interquartile range [IQR], 2.5-13) days in hospital and 3 (IQR, 2-5) days in critical care.

Conclusions: Compared with clinical trial data, we found a numerically higher rate of mortality and similar rate of ATE and VTE among patients treated with idarucizumab in the real world.
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http://dx.doi.org/10.1002/rth2.12535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348998PMC
July 2021

Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: Long-term outcomes from a population-based cohort.

Surgery 2021 09 6;170(3):870-879. Epub 2021 Mar 6.

Division of General Surgery, Department of Surgery, University of Toronto, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Canada; Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Canada; Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Canada. Electronic address:

Background: Red blood cell transfusions are common in patients undergoing gastrointestinal cancer surgery. Yet, to adequately balance their risks and benefits, clinicians must understand how transfusions may affect long-term outcomes. We aimed to determine if perioperative red blood cell transfusions are associated with a higher risk of all-cause and cancer-specific death among patients who underwent gastrointestinal cancer resection.

Method: We identified a population-based cohort of patients who underwent gastrointestinal cancer resection in Ontario, Canada (2007-2019). All-cause death was compared between transfused and nontransfused patients using Cox proportional hazards regression, while cancer-specific death was compared with competing risk regression.

Result: A total of 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) had gastrointestinal cancer surgery during the study period; 20.8% received perioperative red blood cell transfusions. Patients who received red blood cell transfusions had increased hazards of all-cause and cancer-specific death relative to patients who did not (hazard ratio: 1.39, 95% confidence interval 1.34-1.44; cause-specific hazard ratio: 1.36, 1.30-1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months postoperatively) but remained elevated in each interval over 5 years. The association persisted after restricting to patients without postoperative complications or bleeding and was robust to unmeasured confounding.

Conclusion: Red blood cell transfusion among patients with gastrointestinal cancer is associated with increased all-cause death. This was observed long beyond the immediate postoperative period and independent of short-term postoperative morbidity and mortality. These findings should help clinicians balance the risks and benefits of transfusion before well-designed trials are conducted in this patient population.
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http://dx.doi.org/10.1016/j.surg.2021.02.003DOI Listing
September 2021

Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances.

Vox Sang 2021 Sep 26;116(8):898-909. Epub 2021 Feb 26.

Utilization, Efficacy, & Safety of Transfusion (QUEST) Research Program, University of Toronto Quality, Toronto, ON, Canada.

Background/objectives: Transfusion reactions (TRs) may cause or contribute to death. Cardiopulmonary TRs are distressing, and collectively account for most transfusion fatalities, though the degree to which they alter survival more broadly is unclear. Deaths (and their timing) after TRs may provide further insights.

Materials/methods: Adult (tri-hospital network) haemovigilance data (2013-2016) recorded referrals with conclusions ranging from unrelated to transfusion (UTR) to entities such as: septic TRs, serologic/haemolytic reactions, transfusion-associated circulatory overload (TACO), transfusion-associated dyspnoea (TAD), transfusion-related acute lung injury (TRALI), allergic transfusion reaction (ATR), and others. For (in- or out-patient) visits involving suspected TRs (VISTRs), all-cause mortalities (% [95% confidence interval]) and associated time-to-death (TTD) (median days, [interquartile range]) were compared. Diagnoses were defined inclusively (possible-to-definite) or strictly (probable-to-definite).

Results: Of 1144 events, rank order VISTR mortality following (possible-to-definite) TRs, and associated TTDs, were led by: DHTR 33% [6-19], 1 death at 123d; TRALI 32% [15-54], 6 deaths: 3d [2-20]; BaCon 21% [14-31], 17 deaths: 10d [3-28]; TACO 18% [12-26], 23 deaths: 16d [6-28]; TAD 17% [11-26]: 18 deaths, 6d [3-12]. Higher-certainty TRs ranked similarly (DHTR 50% [9-91]; BaCon 29% [12-55], 4 deaths: 12d [3-22]; and TACO 25% [16-38], 15 deaths: 21d [6-28]). VISTR mortality after TACO or TRALI significantly exceeded ATR (3·3% [2·4-5·8], P < 0·00001) but was not different from UTR events (P = 0·3).

Conclusions: Only half of cardiopulmonary TRs constituted high certainty diagnoses. Nevertheless, cardiopulmonary TRs and suspected BaCon marked higher VISTR mortality with shorter TTDs. Short (<1 week) TTDs in TAD, BaCon or TRALI imply either contributing roles in death, treatment refractoriness and/or applicable TR susceptibilities in the dying.
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http://dx.doi.org/10.1111/vox.13086DOI Listing
September 2021

Multicenter observational study evaluating the impact of platelet transport bags on product wastage.

Transfusion 2021 05 11;61(5):1383-1388. Epub 2021 Feb 11.

University of Toronto Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program, Toronto, Ontario, Canada.

Background: Platelets are the most commonly discarded blood product in Canada, with the most common cause of in-date product loss being improper storage. Transport containers to maintain temperature and extend acceptable return time may represent a method to reduce wastage. The objective of this study was to evaluate the impact of a validated Platelet Transport Bag (PTB) on platelet wastage.

Study Design And Methods: Thirty-six hospitals with the highest platelet discards were invited to participate in a before-after observational study. Hospitals were instructed to utilize a validated 4-h PTB for clinical situations where immediate transfusion was not planned. Five hospitals audited in-date platelet discards from July 2018 to November 2019 to characterize wastage causes. In-date platelet discard data 12 months before and after the start date for each site were analyzed to determine changes in wastage.

Results: Of 36 hospital sites, 16 agreed to participate. Pre- and postdiscards were 277 and 301, respectively, for all sites combined. There were no significant before-after change in wastage rate (+0.05%, p = .51). Fifty discards were included in the detailed audit; the most common reasons were return to the blood bank after more than 60 min outside a PTB (n = 17, 34%) and return in a red cell cooler (n = 10, 20%).

Conclusion: Implementation of PTB did not improve wastage. Common causes of in-date discards were return after 1 h outside of a PTB and placement in a red cell cooler in error. Further research is required to investigate potential strategies to mitigate in-date platelet wastage.
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http://dx.doi.org/10.1111/trf.16303DOI Listing
May 2021

Determining Optimal Treatment to Correct Preoperative Anemia and Reduce Perioperative Allogeneic Blood Transfusions in Cardiac Surgery: A Retrospective Cohort Study.

J Cardiothorac Vasc Anesth 2021 09 5;35(9):2631-2639. Epub 2021 Jan 5.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Quality in Utilization, Education and Safety Research Program, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: Preoperative anemia management reduces red blood cell (RBC) transfusion and adverse outcomes, but how best to optimize the patient's hemoglobin (Hgb) before cardiac surgery remains unclear. The authors sought to determine the optimal treatment of anemia using iron and epoetin alfa before cardiac surgery.

Design: Retrospective cohort study.

Setting: Sunnybrook Health Sciences Centre, University of Toronto.

Participants: The study comprised 532 consecutive patients referred to the outpatient Blood Conservation Clinic and who underwent cardiac surgery between 2008 and 2018.

Interventions: Of the 532 patients, 207 received oral iron, 84 received intravenous (IV) iron, 71 received epoetin alfa, 92 received combination therapy, and 78 received no treatment.

Measurements And Main Results: Multivariate linear, logistic, and Poisson regressions modelled preoperative Hgb, the change from referral to preoperative Hgb (∆Hgb), the odds of transfusion, and the number of RBC units transfused, while accounting for baseline covariates. Higher ∆Hgb was associated with IV iron >600 mg (9.80 g/L [6.17-13.42]), epoetin alfa >80,000 U (5.80 g/L [2.20-9.40]), and higher referral Hgb (1.91 g/L [1.09-2.74] per 10 g/L). Higher preoperative Hgb (odds ratio 0.76 [0.64-0.90]; count ratio 0.84 [0.77-0.93] per 10 g/L) corresponded to a lower likelihood of being transfused and transfusion of fewer RBC units.

Conclusions: Preoperative IV iron >600 mg and epoetin alfa >80,000 U each was associated with significant increases in Hgb. Higher preoperative Hgb was associated with a lower likelihood of transfusion and transfusion of fewer RBC units. The authors recommend that cumulative preoperative doses of IV iron >600 mg and epoetin alfa >80,000 U be used for treatment of anemia before cardiac surgery.
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http://dx.doi.org/10.1053/j.jvca.2020.12.044DOI Listing
September 2021

A prospective observational study of the incidence, natural history, and risk factors for intravenous immunoglobulin-mediated hemolysis.

Transfusion 2021 04 12;61(4):1053-1063. Epub 2021 Jan 12.

University of Toronto Quality in Utilization, Education and Safety in Transfusion Research Program (QUEST), Toronto, Canada.

Background: Intravenous Immune Globulin (IVIG) is used to treat numerous immune-mediated and inflammatory conditions. There is growing awareness of hemolysis, occasionally severe, as a side-effect of this therapy. While most cases are associated with anti-A and/or anti-B isoagglutinins, the frequency and mechanism of hemolysis remain poorly characterized.

Study Design And Methods: A prospective observational study was conducted to determine incidence, natural history and risk factors for IVIG-mediated hemolysis. A total of 99 infusions of high-dose IVIG (2 g/kg or higher) administered to 78 non-group O patients were monitored and graded according to Canadian IVIG Hemolysis Pharmacovigilance Group. Serum ferritin and C3/C4 levels were monitored as indicators of macrophage activation and complement consumption, respectively. Supplementary investigations included assessment for ABO zygosity, Secretor status, FcR polymorphisms, eluate IgG subclass, monocyte monolayer assay, and a panel of cytokines.

Results: Hemolysis was observed in 32 of 99 (32%) of infusions, with 19 of 99 (19%) grade 2 or higher. Hemolysis was only apparent 5-10 days after a completed IVIG infusion in 84% of cases and was associated with increases in serum ferritin without complement-consumption. In univariate analysis, increased risk was observed in group AB patients, first-time IVIG recipients, those not taking immuosuppressive medications, or patients treated with a specific IVIG brand; however, in multivariate analysis, product association was no longer observed. No other patient- or practice-related risk factors were identified.

Conclusion: IVIG-mediated hemolysis is common and frequently severe. Monitoring for 5-10 days following an infusion should be considered in non-O patients receiving high-dose IVIG with known risk factors.
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http://dx.doi.org/10.1111/trf.16232DOI Listing
April 2021

A prospective multi-faceted interventional study of blood bank technologist screening of red blood cell transfusion orders: The START study.

Transfusion 2021 02 10;61(2):410-422. Epub 2021 Jan 10.

Department of Transfusion Medicine, Laboratory Services, Grey Bruce Health Services, Owen Sound, Ontario, Canada.

Background: Transfusion of red blood cells (RBC) is a common procedure, which when prescribed inappropriately can result in adverse patient outcomes. This study sought to determine the impact of a multi-faceted intervention on unnecessary RBC transfusions at hospitals with a baseline appropriateness below 90%.

Study Design And Methods: A prospective medical chart audit of RBC transfusions was conducted across 15 hospitals. For each site, 10 RBCs per month transfused to inpatients were audited for a 5-month pre- and 10-month post-intervention period, with each transfusion adjudicated for appropriateness based on pre-set criteria. Hospitals with appropriateness rates below 90% underwent a 3-month intervention which included: adoption of standardized RBC guidelines, staff education, and prospective transfusion order screening by blood bank technologists. Proportions of RBC transfusions adjudicated as appropriate and the total number of RBC units transfused per month in the pre- and post-intervention period were examined.

Results: Over the 15-month audit period, at the 13 hospital sites with a baseline appropriateness below 90%, 1950 patients were audited of which 81.2% were adjudicated as appropriate. Proportions of appropriateness and single-unit orders increased from 73.5% to 85% and 46.2% to 68.2%, respectively from pre- to post-intervention (P < .0001). Pre- and post-transfusion hemoglobin levels and the total number of RBCs transfused decreased from baseline (P < .05). The median pre-transfusion hemoglobin decreased from a baseline of 72.0 g/L to 69.0 g/L in the post-intervention period (P < .0001). RBC transfusions per acute inpatient days decreased significantly in intervention hospitals, but not in control hospitals (P < .001). The intervention had no impact on patient length of stay, need for intensive care support, or in-hospital mortality.

Conclusion: This multifaceted intervention demonstrated a marked improvement in RBC transfusion appropriateness and reduced overall RBC utilization without impacts on patient safety.
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http://dx.doi.org/10.1111/trf.16243DOI Listing
February 2021

Declining Use of Red Blood Cell Transfusions for Gastrointestinal Cancer Surgery: A Population-Based Analysis.

Ann Surg Oncol 2021 Jan 9;28(1):29-38. Epub 2020 Nov 9.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada.

Background: Gastrointestinal cancer surgery patients often develop perioperative anemia commonly treated with red blood cell (RBC) transfusions. Given the potential associated risks, evidence published over the past 10 years supports restrictive transfusion practices and blood conservation programs. Whether transfusion practices have changed remains unclear. We describe temporal RBC transfusion trends in a large North American population who underwent gastrointestinal cancer surgery.

Methods: We conducted a population-based retrospective cohort study of patients who underwent gastrointestinal cancer resection between 2007 and 2018 using health administrative datasets. The outcome was RBC transfusion during hospitalization. Temporal transfusion trends were analyzed with Cochran-Armitage tests. Multivariable regression assessed the association between year of diagnosis and likelihood of RBC transfusion while controlling for confounding.

Results: Of 79,764 patients undergoing gastrointestinal cancer resection, the median age was 69 years old (interquartile range (IQR) 60-78 years) and 55.5% were male. The most frequent procedures were colectomy (52.8%) and proctectomy (23.0%). A total of 18,175 patients (23%) received RBC transfusion. The proportion of patients transfused decreased from 26.5% in 2007 to 18.9% in 2018 (p < 0.001). After adjusting for patient, procedure, and hospital factors, the most recent time period (2015-2018) was associated with a reduced likelihood of receiving RBC transfusion [relative risk 0.86 (95% confidence interval: 0.83-0.89)] relative to the intermediate time period (2011-2014).

Conclusion: Over 11 years, we observed decreased RBC transfusion use and reduced likelihood of transfusion in patients undergoing gastrointestinal cancer resection. This information provides a foundation to further examine transfusion appropriateness or explore if additional transfusion minimization in surgical patients can be achieved.
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http://dx.doi.org/10.1245/s10434-020-09291-yDOI Listing
January 2021

TACO-BEL-3: a feasibility study and a retrospective audit of diuretics for patients receiving blood transfusion at ten hospitals.

Vox Sang 2021 Apr 26;116(4):434-439. Epub 2020 Oct 26.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Background And Objectives: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related morbidity and mortality. A recently completed pilot trial randomized patients to pre-transfusion furosemide versus placebo but had a slower than expected enrollment rate. We sought to determine whether the lack of recruitment was due to a paucity of eligible patients or excessively restrictive eligibility criteria.

Materials And Methods: At 10 sites, eligible patients were retrospectively identified by first screening blood bank databases over one month for all transfusion episodes meeting trial inclusion criteria, defined as non-surgical patients receiving single RBC unit transfusions. The age threshold was decreased from 65 to 50 years. The first 10 patients meeting inclusion criteria then underwent detailed chart review for the exclusion criteria. The incidence of TACO and furosemide use was also recorded.

Results: At the 10 sites, 11 969 red cell units were transfused over 1 month and 1356 met the inclusion criteria. Of the 100 charts reviewed, 60 (60%) had no exclusion criteria. Active bleeding was the most common reason for ineligibility. There were 813 eligible transfusion episodes. Of the eligible patients, 17 (28·3%) had evidence of congestive heart failure, and furosemide was prescribed in 24 (40%). Despite the use of a lower age threshold, three cases of TACO were detected with an incidence of 3%.

Conclusion: A large number of transfusion episodes met eligibility criteria. With a 3% incidence of TACO, 50% decrease through the use pre-transfusion furosemide and a target consent rate of 30%, a definitive trial of approximately 3000 patients could be completed within 1 year.
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http://dx.doi.org/10.1111/vox.12994DOI Listing
April 2021

The utility of a monocyte monolayer assay in the assessment of intravenous immunoglobulin-associated hemolysis.

Transfusion 2020 12 22;60(12):3010-3018. Epub 2020 Oct 22.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Background: Hemolysis following the administration of intravenous immunoglobulin (IVIG) is an important adverse event (AE). While the monocyte monolayer assay (MMA) has been used to predict in vivo hemolysis when serologically incompatible blood may be transfused, it has also been shown to correlate with IVIG-associated hemolysis. In this study, the MMA was examined for its utility in assessing the risk of hemolysis after IVIG.

Study Design And Methods: Forty-two non-blood group O patients receiving high-dose IVIG (≥2 g/kg) were examined using an autologous and allogeneic MMA. Hemolysis was defined by a drop in hemoglobin of ≥1 g/L, a positive direct antiglobulin test (DAT) and eluate, and a decrease in haptoglobin or increase in lactate dehydrogenase and/or reticulocytes.

Results: Forty-two patients provided 50 assessable postinfusion samples, with hemolysis observed in 20 (40%) of cases. Autologous MMA using post-IVIG red blood cells significantly correlated with clinical outcomes when compared to allogeneic MMA (P = .0320 vs .5806, t test). No significant difference in receiver operating characteristics was observed when comparing autologous MMA testing against DAT for the diagnosis of IVIG-associated hemolysis. However, when using samples collected 5 to 10 days after receipt of high-dose IVIG, the autologous MMA had higher sensitivity than the DAT.

Conclusion: MMA testing with autologous monocytes collected 5 to 10 days after receipt of high-dose IVIG can be used for the diagnosis of IVIG-associated hemolysis and may be of particular value in cases in which the Day 5 to 10 DAT is negative.
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http://dx.doi.org/10.1111/trf.16131DOI Listing
December 2020

Evaluating the appropriateness of platelet transfusions compared with evidence-based platelet guidelines: An audit of platelet transfusions at 57 hospitals.

Transfusion 2021 01 20;61(1):57-71. Epub 2020 Oct 20.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Platelet transfusions are used to prevent or control bleeding in patients with thrombocytopenia or platelet dysfunction. The pretransfusion platelet count threshold has been studied extensively in multiple patient settings yielding high-quality evidence that has been summarized in several comprehensive evidence-based platelet guidelines.

Study Design And Methods: A prospective 12-week audit of consecutive platelet transfusions using validated and evidence-based adjudication criteria was conducted. Patient demographic, laboratory, and transfusion details were collected with an electronic audit tool. Each order was adjudicated either electronically or independently by two transfusion medicine physicians. The aim was to determine platelet transfusion appropriateness and common scenarios with deviations from guidelines.

Results: Fifty-seven (38%) of 150 hospitals provided data on 1903 platelet orders, representing 90% of platelet usage in the region during the time period. Overall, 702 of 1693 adult (41.5%) and 133 of 210 pediatric orders (63.3%) were deemed inappropriate. The most common inappropriate platelet order was for prophylaxis in the absence of bleeding or planned procedure in patients with hypoproliferative thrombocytopenia and a platelet count over 10 x 10 /L (53% of inappropriate orders in adults and 45% in pediatrics). Platelet transfusions ordered with either a preprinted transfusion order set (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.44-2.73) or technologist prospective screening (OR, 1.40; 95% CI, 1.10-1.78) were more likely to be appropriate.

Conclusion: There is a discrepancy between clinical practice and evidence-based platelet guidelines. Broad educational and system changes will be needed to align platelet transfusion practice with guideline recommendations.
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http://dx.doi.org/10.1111/trf.16134DOI Listing
January 2021

Physician Factors Associated with Inappropriate Vitamin B12 Prescribing in Ontario, Canada.

J Gen Intern Med 2021 09 9;36(9):2888-2890. Epub 2020 Sep 9.

Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s11606-020-06185-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390716PMC
September 2021

Impact of red blood cell alloimmunization on fetal and neonatal outcomes: A single center cohort study.

Transfusion 2020 11 7;60(11):2537-2546. Epub 2020 Sep 7.

Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Background: Alloimmunization can impact both the fetus and neonate.

Study Objectives: (a) calculate the incidence of clinically significant RBC isoimmunization during pregnancy, (b) review maternal management and neonatal outcomes, (c) assess the value of prenatal and postnatal serological testing in predicting neonatal outcomes.

Study Design And Methods: A retrospective audit of consecutive alloimmunized pregnancies was conducted. Data collected included demographics, clinical outcomes, and laboratory results. Outcomes included: incidence of alloimmunization; outcomes for neonates with and without the cognate antigen; and sensitivity and specificity of antibody titration testing in predicting hemolytic disease of the fetus and newborn (HDFN).

Results: Over 6 years, 128 pregnant women (0.4%) were alloimmunized with 162 alloantibodies; anti-E was the most common alloantibody (51/162; 31%). Intrauterine transfusions (IUTs) were employed in 2 (3%) of 71 mothers of cognate antigen positive (CoAg+) neonates. Of 74 CoAg+ neonates, 58% required observation alone, 23% intensive phototherapy, 9% top up transfusion, and 3% exchange transfusion; no fetal or neonatal deaths occurred. HDFN was diagnosed in 28% (21/74) of neonates; anti-D was the most common cause. The sensitivity and specificity of the critical gel titer >32 in predicting HDFN were 76% and 75%, respectively (negative predictive value 95%; positive predictive value 36%). The sensitivity and specificity of a positive direct antiglobulin test (DAT) in predicting HDFN were 90% and 58%, respectively (NPV 97%; PPV 29%).

Conclusion: Morbidity and mortality related to HDFN was low; most alloimmunized pregnancies needed minimal intervention. Titers of >32 by gel warrant additional monitoring during pregnancy.
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http://dx.doi.org/10.1111/trf.16061DOI Listing
November 2020

Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial.

Lancet Haematol 2020 Sep;7(9):e640-e648

Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; McMaster Centre for Transfusion Research, Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Background: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin.

Methods: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 10 cells per L before major surgery or less than 50 × 10 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 10 cells per L before major surgery or 45 × 10 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204.

Findings: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; p=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; p=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred.

Interpretation: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles.

Funding: GlaxoSmithKline and Novartis.
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http://dx.doi.org/10.1016/S2352-3026(20)30227-1DOI Listing
September 2020

Educating the next frontier of transfusionists: a transfusion camp pilot program for nurse practitioners.

Transfusion 2020 06 20;60(6):1142-1148. Epub 2020 Mar 20.

Vancouver Coastal Health Authority, Vancouver, British Columbia, Canada.

Background: Blood transfusion is common and potentially lifesaving but is associated with risk and overuse. Nurse practitioners (NPs) in multidisciplinary care teams are increasingly expanding their scope of practice to transfusion medicine (TM). Resources aimed at NPs are lacking, and little is known about NP TM knowledge. Thus, we developed a pilot TM curriculum for NP credentialing and assessed its impact.

Methods: NP leads and TM directors adapted the successful Canadian Transfusion Camp for medical postgraduate trainees into a 3-day curriculum for NPs. Two modalities were used to assess the pilot: 1) a participant demographics survey and needs assessment; and 2) the validated BEST-TEST knowledge assessment exam administered before and after the course.

Results: Of the 23 volunteer participants, the majority reported prescribing blood products within the last year, primarily red blood cells. Minimal opportunities to undertake continuing medical education in TM were identified. NPs often used preprinted order forms, consultation with physicians sharing care, or local fact sheets to guide transfusion; rather than TM physician consultation or guidelines. Exam scores significantly improved after the course (before, 35.2% vs. after, 50.3%; p = 0.005), suggesting average initial knowledge being below medical postgraduate trainee-level improving to postgraduate trainee level. Questions on appropriate transfusion triggers and correct recipient identification were most correctly answered; and responses to transfusion reaction questions required improvement.

Conclusions: Our needs assessment suggests that TM resources for NPs are relevant but lacking. Our initiative supports the generalizability, scalability, and effectiveness of the Transfusion Camp program. Further implementation, refinement, and future impact assessments are required.
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http://dx.doi.org/10.1111/trf.15755DOI Listing
June 2020

Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial.

Br J Haematol 2020 04 20;189(2):279-290. Epub 2020 Jan 20.

Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.

Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow-up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ-C30 and EQ-5D-5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80 g/l, to maintain haemoglobin 85-100 g/l) with liberal thresholds (105 g/l, maintaining 110-125 g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n = 20 restrictive; n = 18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention-to-treat population was 86% (95% confidence interval 75-94%) and 99% (95-100%) for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient-centred outcomes.
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http://dx.doi.org/10.1111/bjh.16347DOI Listing
April 2020

Preoperative anemia-screening clinics.

Authors:
Yulia Lin

Hematology Am Soc Hematol Educ Program 2019 12;2019(1):570-576

Transfusion Medicine and Tissue Bank, Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Preoperative anemia is associated with increased postoperative morbidity and mortality and with increased risk of perioperative transfusion. It is an important and modifiable risk factor for surgical patients. For high-blood-loss surgery, preoperative anemia is defined as hemoglobin <13 g/dL for both male and female patients. Preoperative anemia is common, ranging from 25% to 40% in large observational studies. The most common treatable cause of preoperative anemia is iron-deficiency anemia; the initial laboratory tests should focus on making this diagnosis. Management of iron-deficiency anemia includes iron supplementation with IV iron therapy when oral iron is ineffective or not tolerated, there is severe anemia, and there is insufficient time to surgery (<4 weeks). In other situations, erythropoiesis-stimulating agents may be considered, particularly for those patients with multiple alloantibodies or religious objections to transfusion. To facilitate the diagnosis and management of preoperative anemia, establishment of preoperative anemia-screening clinics is essential. The goals of management of preoperative anemia are to treat anemia, reduce the need for transfusion, and improve patient outcomes.
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http://dx.doi.org/10.1182/hematology.2019000061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913451PMC
December 2019

Vitamin B12 Therapy in Older Adults and Misconception of Its Inappropriateness-Reply.

JAMA Intern Med 2019 11;179(11):1606-1607

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jamainternmed.2019.4902DOI Listing
November 2019

A retrospective study of the added value of parallel titers compared with serial titers.

Transfusion 2019 10 4;59(10):3084-3088. Epub 2019 Sep 4.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Prenatal antibody titers for alloimmunized patients are subject to multiple sources of variation. A parallel titer on the previous sample at the same time as the current sample is recommended. The purpose of this study was to determine the added value of parallel titers.

Study Design And Methods: This is a retrospective study of samples from consecutive prenatal patients with at least two prenatal antibody titers performed in the same pregnancy at a single institution between October 2010 and March 2017. Prenatal titers were performed using gel technology. Data were collected to determine the sensitivity and specificity of a clinically significant increase (twofold or greater) in serial titers compared with the gold standard of using parallel titers.

Results: There were 155 serial prenatal titers performed in 59 alloimmunized pregnant women. Nineteen samples (12%) had a serial titer increase of twofold or greater with eight false positive samples (increase less than twofold when using parallel titers). Thirty-six samples (23%) had a serial titer increase of onefold with two false negative samples (increase of twofold or greater using parallel titers). One hundred samples (65%) had no increase (or a decrease) in serial titer with none having an increase of twofold or greater using parallel titers. The sensitivity of a twofold or greater increase in serial titers was 84.6% (95% CI 55-98%) and the specificity was 94.4% (95% CI 89-98%) when compared with parallel titers.

Conclusion: This study questions the value of parallel titers on every prenatal titer performed. When no increase in serial titers was observed, parallel titers added no new information.
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http://dx.doi.org/10.1111/trf.15505DOI Listing
October 2019

Serologic assessments in acute transfusion reactions: practices and yields.

Vox Sang 2019 Oct 7;114(7):749-761. Epub 2019 Aug 7.

University of Toronto Quality, Efficacy & Safety in Transfusion (QUEST) Research Program, Utilization, Toronto, Ontario, Canada.

Background & Objectives: Serologic testing after transfusion reactions (TRs) aims to find accountable immune haemolytic incompatibility. Our hospital policies recommend serologic testing in all TR, except for low-risk fevers (subclinical temperature <39°C) or uncomplicated allergic reactions. Assessing compliance with these guidelines and serologic testing yields may provide insights on quality of practice and value.

Materials & Methods: Interrogation of two haemovigilance databases identified all possible-to-definite TR over a 4-year period (2013-2016) at four academic hospitals. We reviewed the performance and outcome of serologic testing by site, year, reaction type, implicated product and service.

Results: Serologic testing occurred in 769 (55%) of 1408 referrals, with 1153 (82%) compliant with guidelines. Similar proportions deviated to overtesting (85/550 [15%]) and undertesting (174/858 [20%]), with undertesting seen most often in atypical TR. Overall, 30 (4.4%) of 769 cases had a new finding, but only 2 (0.3%) reflected host-derived antibodies. Overall, the number needed to test to discover an unexpected allospecificity was 385, or 253 if limited to high-risk fevers. Reaction- and product-specific yields ranged from 0% to 48%. The yield in complicated allergic reactions was low at 2%, constituting only predictable passive isohaemagglutinin(s) in retrospect. Investigated IVIG TR accounted for most of this cohort's signal by passive isohaemagglutinins in 48%.

Conclusion: The performance of post-TR serologic testing revealed practice gaps and expected context-specific yields. Tailored serologic testing (i.e. indirect antiglobulin tests for alloantibodies in post-RBC/high-risk febrile reactions, ± isoagglutinin-focused tests after IVIG or ABO-minor-mismatched platelets) may improve value and liberate resources for other unmet needs in TR investigation.
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http://dx.doi.org/10.1111/vox.12830DOI Listing
October 2019

Outpatient transfusions: time to study what matters to patients.

Transfusion 2019 06;59(6):1887-1890

Division of Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

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http://dx.doi.org/10.1111/trf.15382DOI Listing
June 2019

Pseudo heparin resistance caused by elevated factor VIII in a critically ill patient.

Can J Anaesth 2019 Aug 10;66(8):995-996. Epub 2019 May 10.

University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s12630-019-01391-yDOI Listing
August 2019

Transfusion Camp: a prospective evaluation of a transfusion education program for multispecialty postgraduate trainees.

Transfusion 2019 06 4;59(6):2141-2149. Epub 2019 Apr 4.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Canada.

Background: The optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes, and self-reported behavior was evaluated.

Methods: Didactic lectures (delivered locally, by webinar, or recorded) and locally facilitated team-based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20-question multiple-choice exam was conducted before and after Transfusion Camp. Attitudes and self-reported behavior were collected through a survey.

Results: Over 2 academic years (July 2016 to June 2018), 390 trainees from 16 different specialties (predominantly anesthesia, 41%; hematology, 14%; and critical care, 7%) attended at least 1 day of Transfusion Camp. The mean pretest score was 10.3 of 20 (±2.9; n = 286) compared with posttest score of 13.0 (±2.8; n = 194; p < 0.0001). Lower pretest score and greater attendance (4-5 days compared with 1-3 days) were associated with larger improvement in posttest score; delivery format, specialty, and postgraduate year were not. Trainees reported an improvement in self-rated abilities to manage TM scenarios; 95% rated TM knowledge as very or extremely important in providing patient care; and 81% indicated that they had applied learning from Transfusion Camp into clinical practice.

Conclusions: Transfusion Camp increased TM knowledge, fostered a positive attitude toward TM, and enabled a self-reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.
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http://dx.doi.org/10.1111/trf.15284DOI Listing
June 2019

Canadian expert consensus: management of hypersensitivity reactions to intravenous iron in adults.

Vox Sang 2019 May 2;114(4):363-373. Epub 2019 Apr 2.

Department of Medicine, Division of Gastroenterology, McMaster University Medical Centre, McMaster University, Hamilton, ON, Canada.

Background And Objectives: Rare but potentially life-threatening hypersensitivity reactions can occur during the administration of intravenous iron. To provide guidance to healthcare professionals caring for adults receiving intravenous iron, a panel of 10 Canadian clinical experts developed a practical algorithm for the identification and management of hypersensitivity reactions to intravenous iron.

Materials And Methods: A systematic search of PubMed to February 2018 was performed. Articles related to hypersensitivity reactions were selected for review. The algorithm was developed during a 1-day live meeting based on the literature review and clinical expertise where evidence was lacking. The algorithm was then refined through an iterative process involving a web-based platform and virtual meetings.

Results: The algorithm provides guidance to healthcare professionals in preparing for and administering IV iron, as well as recognizing and managing hypersensitivity reactions to intravenous iron. Considerations for re-challenging patients who have experienced prior reactions are provided.

Conclusion: Healthcare professionals who are involved in the care of patients receiving intravenous iron should be trained to anticipate, recognize and manage hypersensitivity reactions to intravenous iron to optimize patient care.
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http://dx.doi.org/10.1111/vox.12773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850285PMC
May 2019
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