Zoe McQuilten

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors

Background Currently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency. Design and Methods Sera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzyme-linked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency. Results In 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20.4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2–199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%. Conclusions Serum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion

The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults

BACKGROUND It is uncertain whether the duration of red‐cell storage affects mortality after transfusion among critically ill adults. METHODS In an international, multicenter, randomized, double‐blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short‐term storage group) or standard‐issue (oldest available), compatible, allogeneic red cells (long‐term storage group). The primary outcome was 90‐day mortality. RESULTS From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short‐term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long‐term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short‐term storage group and 594 (24.1%) in the long‐term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], ‐1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, ‐2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between‐group differences in outcome. CONCLUSIONS The age of transfused red cells did not affect 90‐day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886; ClinicalTrials.gov number, NCT01638416.)

A review of pathophysiology and current treatment for neonatal alloimmune thrombocytopenia (NAIT) and introducing the Australian NAIT registry

Fetomaternal or neonatal alloimmune thrombocytopenia (NAIT) is a rare but serious condition associated with significant fetal and neonatal morbidity and mortality. The most useful predictor of severe disease is a history of a sibling with an antenatal intracranial haemorrhage. However, NAIT can occur during the first pregnancy and may not be diagnosed until the neonatal period. Antenatal treatment options include maternal intravenous immunoglobulin (IVIG) and corticosteroid treatment, fetal blood sampling (FBS) and intrauterine platelet transfusion (IUT) and early delivery. FBS (with or without IUT) can be used to direct and monitor response to therapy, and to inform mode and timing of delivery. However, this procedure is associated with significant risks, including fetal death, and is generally now reserved for high‐risk pregnancies. This review highlights the current understanding of the epidemiology and pathophysiology of NAIT and summarises current approaches to investigation and management. It also introduces the newly established Australian NAIT registry. Owing to the relative rarity of NAIT, accruing sufficient patient numbers for studies and clinical trials at an institutional level is difficult. This national registry will provide an opportunity to collect valuable information and inform future research on this condition.

Off-Label Use of Recombinant Factor VIIa in Pediatric Patients

OBJECTIVE: To examine off-label recombinant factor VIIa (rFVIIa) use in pediatric patients including clinical indications, dose, adverse events, and outcomes. METHODS: All pediatric patients entered into the Haemostasis Registry from 75 participating hospitals were analyzed. RESULTS: Three hundred and eighty-eight pediatric patients received off-label rFVIIa from 2003 to 2009. Median age was 12 months (interquartile range 1 month to 11 years). Clinical context included cardiac surgery (52.1%), medical (11.6%), other surgery (10.8%), hematology/oncology (10.3%), trauma (9.3%), intracranial hemorrhage (3.1%), and liver disease (2.8%). Twenty-six patients received extracorporeal membrane oxygenation at the time of rFVIIa administration. Median first dose was 114 μg/kg (interquartile range 90–181; range 7–2250). Thirty-four percent received >1 dose. There was a reduction in usage of red blood cells, platelets, fresh-frozen plasma, and cryoprecipitate in the 24 hours after the first dose for all patients (all P values < .001). Thromboembolic adverse events (TEAs) were reported in 5.4%. No association between TEA and size of first dose was found. Where data were available, 82% of patients were subjectively classified as responding to rFVIIa. Overall 28-day mortality was 27%. In multivariate analysis, pH values before administration and clinical context were independently associated with response to first dose and 28-day mortality. CONCLUSIONS: There was a significant reduction in blood product administration after rFVIIa and a subjective response rate of 82%. Both pH and clinical context were associated with response to rFVIIa and mortality. Overall, 5.4% had a TEA reported.

Underestimation of myelodysplastic syndrome incidence by cancer registries: Results from a population‐based data linkage study

Myelodysplastic syndromes (MDS) appear to be underreported to cancer registries, with important implications for cancer and transfusion support service planning and delivery. Two population‐based databases were linked to estimate MDS incidence more accurately.

Hemoglobin and iron indices in nonanemic premenopausal blood donors predict future deferral from whole blood donation.

BACKGROUND: Iron deficiency anemia is an important reason for blood donor deferral. We prospectively determined whether screening donors with hemoglobin (Hb) and iron indices before donation can predict subsequent deferral due to anemia.

African culturally and linguistically diverse communities' blood donation intentions in Australia: integrating knowledge into the theory of planned behavior.

The Theory of Planned Behavior (TPB) has been extensively used to examine donation intentions in the general community. This research seeks to examine whether TPB applies to one culturally and linguistically diverse (CALD) community in Australia and also incorporates blood donation knowledge as an antecedent in the model, given that the TPB assumes people make informed decisions regarding blood donation.

Transfusion interventions in critical bleeding requiring massive transfusion: a systematic review

Critical bleeding (CB) requiring massive transfusion (MT) can occur in a variety of clinical contexts and is associated with substantial mortality and morbidity. In 2011, the Australian National Blood Authority (NBA) published patient blood management guidelines for CB and MT, which found limited high-quality evidence from which only 2 recommendations could be made. The aim of this systematic review (SR) was to update these guidelines and identify evidence gaps still to be addressed. A comprehensive search was performed for randomized controlled trials (RCTs) and SRs using MeSH index and free text terms in MEDLINE, the Cochrane Library (Issue 11, 2012), EMBASE, CINHAL, PUBMED, and the Transfusion Evidence Library up to July 15, 2014. The evidence was grouped according to 4 questions based on the original guideline relating to transfusion interventions: (1) effect of dose, timing, and ratio of red blood cells (RBCs) to component therapy on patient outcomes; (2) effect of RBC transfusion on patient outcomes; (3) effect of fresh frozen plasma, platelet, cryoprecipitate, fibrinogen concentrate, and prothrombin complex concentrate on patient outcomes; and (4) effect of recombinant activated factor VII (rFVIIa) on patient outcomes. From this search, 19 studies were identified: 6 RCTs and 13 SRs. Two of the RCTs were pilot/feasibility studies, 3 were investigating rFVIIa, and 1 compared restrictive versus liberal RBC transfusion in upper gastrointestinal hemorrhage. Overall, limited new evidence was identified and substantial evidence gaps remain, particularly with regard to the effect of component therapies, including ratio of RBC to component therapies, on patient outcomes. Clinical trials to address these questions are required.

Duration of red blood cells storage and outcome in critically ill patients.

PURPOSE There is conflicting evidence on the effect of red blood cells (RBC) storage duration and clinical outcomes. We aimed to investigate the association between RBC storage duration and clinical outcomes in patients admitted to the intensive care unit (ICU). MATERIALS AND METHODS We retrospectively (2001-2011) studied adults admitted to the ICUs of 2 hospitals who received RBC. Using the mean, maximum and minimum age of RBC units transfused, we evaluated the association between RBC storage duration and mortality. We also analyzed the association between mean age of RBC units and length of stay (LOS) in survivors. We performed sensitivity analyses in patients who only received RBC in ICU and who only received leukodepleted RBC. RESULTS We studied 8416 patients who received a median of 4 (interquartile range, 2-7) RBC units. After multivariate analysis, age of RBC was not independently associated with mortality, including in the subgroup analyses. Furthermore, there was no clinically relevant relationship between mean RBC age and LOS. CONCLUSIONS RBC storage duration was not associated with increased mortality nor ICU and hospital LOS. These results support the view that the effect of RBC storage duration on outcomes in critically ill patients is uncertain.