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Acquired hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). No previous systematic reviews (SRs) have compared different approaches to infection prevention. We sought to assess the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in these patients. We performed an SR and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in adult patients with hematological malignancies commonly associated with acquired hypogammaglobulinemia, specifically, CLL, NHL, and MM. We searched PubMed (MEDLINE), EMBASE, and Cochrane Registry up to 9 January 2021. Results for dichotomous data were expressed as relative risk (RR) with 95% confidence interval (CI) and pooled in a random-effects model. This review was registered with PROSPERO CRD42017070825. From 10 576 studies screened, there were 21 completed RCTs and 1 ongoing. Of these, 8 evaluated prophylactic immunoglobulin (n = 370; 7 published before 2000), 5 evaluated prophylactic antibiotics (n = 1587), 7 evaluated vaccination (n = 3996), and 1 compared immunoglobulin to antibiotics (n = 60). Prophylactic immunoglobulin reduced the risk of clinically documented infection (CDI) by 28% (n = 2 trials; RR, 0.72; 95% CI, 0.54-0.96), and vaccination reduced the risk by 63% (RR, 0.37; 95% CI, 0.30-0.45). Prophylactic antibiotics did not reduce the risk. No intervention reduced all-cause mortality. Prophylactic immunoglobulin and antibiotics increased the risk of adverse events. Findings should be interpreted with caution, given the high risk of bias in many studies. There is a clear need for high-quality contemporary trials to establish the effectiveness of different approaches to preventing infection.

Comprehensive clinical characteristics of Australian patients with classical Hodgkin Lymphoma (cHL) have not previously been systematically collected and described. We report real-world data of 498 eligible patients from the first five years of the Lymphoma and Related Diseases Registry (LaRDR), including baseline characteristics, histologic subtype and treatment patterns in first-line therapy. Patient demographics and distribution of histopathological subtypes of cHL are similar to reported international cohorts. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most common therapy for both early and advanced-stage disease, and 48% of patients with early-stage disease received radiotherapy. Treatment patterns are consistent with international guidelines. In comorbid patients ≥ 60 years of age with advanced-stage disease, there is greater variation in treatment. In patients with a recorded response, the objective response rate (ORR) was 96% in early-stage disease, and 88% in advanced-stage disease. Early progression-free survival data suggest Australian patients with cHL have good outcomes, similar to other international studies.

West Nile virus (WNV) is a potentially transfusion-transmissible virus endemic in the US. The aim of this study was to estimate the monthly WNV transfusion transmission (TT) risk in Australia associated with donors returning from the US in 2018 and consider the implications for mitigation strategies.We used a probabilistic risk model to estimate the monthly WNV TT risks for each outbreak state/district in the US for the 2018 transmission season and the cumulative monthly risk for all US states/districts.The highest monthly cumulative transfusion risk in Australia occurred in August 2018 when 746 West Nile neuroinvasive disease cases were reported in the US and the estimated mean WNV TT risk in Australia was 1 in 1.0 × 10Our modeling indicates that the WNV TT risk in Australia associated with seasonal outbreaks in the US is extremely small and may not warrant donation restrictions for donors returning from the US.

Myelodysplastic syndromes (MDS) have a major impact on quality of life (QoL). We performed a

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in thein vivoconcentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 54-fold of thein vitroIC50 (95% CI: 16 – 183). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants.Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination.

Background Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence. We aimed to describe the contemporary management and outcomes of patients with FNAIT in high-income countries.Methods In this multicentre, retrospective, cohort study, we set up a web-based registry for the collection of deidentified data on the management and course of neonates with FNAIT. Eight centres from seven countries (Australia, Norway, Slovenia, Spain, Sweden, the Netherlands, and the USA) participated. Eligibility criteria comprised neonates with FNAIT being liveborn between Jan 1, 2010, and Jan 1, 2020; anti-human platelet antigen (HPA) alloantibodies in maternal serum; confirmed maternal and fetal HPA incompatibility; and bleeding detected at antenatal ultrasound, neonatal thrombocytopenia (

Bone lesions and other disease- and treatment-related side effects commonly experienced by people with multiple myeloma (MM) may impede their ability to exercise. This systematic review evaluated the safety, feasibility, and efficacy of exercise program participation on the physiological and/or psychological health of people with MM. Literature searches were conducted through five electronic databases and appraised using the Delphi list of criteria. Controlled trials that assessed the safety and feasibility of an exercise intervention and its effects on disease- or treatment-related symptoms in people with MM were included. Seven studies of varying quality involving 563 participants were included. All studies concluded that exercise was safe, reporting zero serious and 4 adverse events attributable to exercise testing or training. Attendance ranged from 58% to 96%, however no study reported adherence to the exercise prescription. Compared to a control group, exercise did not appear to affect fatigue, depression, anxiety, body composition, quality of life, or sleep. Isolated studies identified between-group differences favoring exercise in lower limb strength (+8.4 kg, 95% CI 0.5, 16.3, P= .04), peak oxygen uptake (+1.2 mL/kg/min, 95% CI 0.3, 3.7, P= .02), physical activity (+6.5MET-hs/wk, P.001), stem cell collection attempts (1.1 ± 0.2 vs. 1.5 ± 0.9, P.01), and red blood cell (1.8 ± 2.2 vs. 2.4 ± 2.6, P.05) and platelet transfusions (2.3 ± 1.6 vs. 3.5 ± 3.4, P.05) during transplantation. Exercise interventions appear safe and well attended by people with MM. The lack of improvements in disease- and treatment-related symptoms requires further exploration to determine whether exercise is a sufficient stimulus to elicit benefits in this unique population.

In the context of critical bleeding and massive transfusion (CB/MT), little is known about the development of new red blood cell (RBC) alloantibodies. We performed a retrospective, observational study to examine the frequency of RBC alloantibodies (pre-existent, anamnestic, or new) in patients with CB/MT, defined as transfusion of five or more RBC units in any 4-hour period, for any cause of CB.Data on 2,585 New Zealand patients (date/time of MT initiation, demographic data, blood group, clinical context, and transfused RBCs) were obtained from the Australian and New Zealand Massive Transfusion Registry. RBC alloantibody screening/identification data were extracted from the New Zealand Blood Service database. We calculated summary statistics, compared proportions between different independent groups using the Chi-squared test, and performed logistic regression analysis to examine the effects of variables on alloantibody presence or formation. We also determined the immunogenicities of selected RBC antigens in the context of CB/MT.Of 1,234 assessable patients, 1,166 (94.5%) showed no evidence of any alloantibody. Pre-existent, anamnestic, and new alloantibodies were found, respectively, in 4.3%, 0.4%, and 7.2% of assessable patients. By multivariable regression analysis, transfusion of D-positive RBC to D-negative patients was independently associated with new alloantibody formation. Neither the quantum of RBC transfused nor trauma as clinical context were so associated although the latter trended towards a predisposition. "Antibodies of undetermined specificity" were the commonest pre-existent and new alloantibodies. The immunogenicity of JkRBC alloantibodies of any type were rare in this CB/MT population. Patients undergoing CB/MT appear to have low risks of re-stimulating anamnestic alloantibodies, or of developing new RBC alloantibodies.

Home blood product transfusion has been utilized around the world in various forms over the past few decades. There is current interest in decentralizing hospital care to improve patient independence and convenience, minimize cost to the health service, and to prevent nosocomial infection, especially with the recent COVID-19 pandemic. The transition to "hospital in the home" is occurring across the healthcare sector driven by aims to improve patient outcomes and patient satisfaction, capacity pressures in the acute care sector, and most recently due to concerns regarding infectious disease transmission in hospital settings. This review explores the published literature on home red cell and platelet transfusions, and where the literature is limited, also considered data from subcutaneous immunoglobulin studies. Current published experience on red cell and platelet transfusion at home has identified benefits to the patient and health service, with further studies needed to quantify improvement in quality of life and health-related outcomes. Safety concerns may be a perceived barrier to implementation of home transfusion, however current published data suggests serious adverse reactions are rare. Cost-effectiveness data for home transfusion are very limited and a key area for future research. Home transfusion has the potential to benefit from newer technologies, such as portable/remote monitoring and electronic patient identifiers.

SummaryBackgroundA large number of studies have been carried out involving passive antibody administration for the treatment and prophylaxis of COVID-19 and have shown variable efficacy. However, the determinants of treatment effectiveness have not been identified. Here we aimed to aggregate all available data on randomised controlled trials of passive antibody treatment for COVID-19 to understand how the dose and timing affect treatment outcome.MethodsWe analysed published studies of passive antibody treatment from inception to 7 January 2022 that were identified after searching various databases such as MEDLINE, Pubmed, ClinicalTrials.gov. We extracted data on treatment, dose, disease stage at treatment, and effectiveness for different clinical outcomes from these studies. To compare administered antibody levels between different treatments, we used data on in vitro neutralisation of pseudovirus to normalise the administered dose of antibody. We used a mixed-effects regression model to understand the relationship between disease stage at treatment and effectiveness. We used a logistic model to analyse the relationship between administered antibody dose (normalised to the mean convalescent titre) and outcome, and to predict efficacy of antibodies against different Omicron subvariants.FindingsWe found that clinical stage at treatment was highly predictive of the effectiveness of both monoclonal antibodies and convalescent plasma therapy in preventing progression to subsequent stages (pInterpretationEarly administration of passive antibody therapy is crucial to achieving high efficacy in preventing clinical progression. A dose-response curve was derived for passive antibody therapy administered to ambulant symptomatic subjects to prevent hospitalisation. For many of the monoclonal antibody regimens analysed, the administered doses are estimated to be between 7 and >1000 fold higher than necessary to achieve 90% of the maximal efficacy against the ancestral (Wuhan-like) virus. This suggests that a number of current treatments should maintain high efficacy against Omicron subvariants despite reduction in in vitro neutralisation potency. This work provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19.FundingThis work is supported by an Australian government Medical Research Future Fund awards GNT2002073 and MRF2005544 (to MPD, SJK), MRF2005760 (to MPD), an NHMRC program grant GNT1149990 (SJK and MPD), and the Victorian Government (SJK). SJK is supported by a NHMRC fellowship. DC, MPD, ZKM and EMW are supported by NHMRC Investigator grants and ZKM and EMW by an NHMRC Synergy grant (1189490). DSK is supported by a University of New South Wales fellowship. KLC is supported by PhD scholarships from Monash University, the Haematology Society of Australia and New Zealand and the Leukaemia Foundation. TT, HW and CB are members of the National COVID-19 Clinical Evidence Taskforce which is funded by the Australian Government Department of Health.Research in contextEvidence before this studyWe identified randomised controlled trials (RCTs) evaluating the effectiveness of SARS-CoV-2-specific neutralising monoclonal antibodies, hyperimmune immunoglobulin and convalescent plasma in the treatment of participants with a confirmed diagnosis of COVID-19 and in uninfected participants with or without potential exposure to SARS-CoV-2. The RCTs were identified from published searches conducted by the Cochrane Haematology living systematic review teams.A total of 37 randomised controlled trials (RCT) of passive antibody administration for COVID-19 were identified. This included 12 trials on monoclonal antibodies, 21 trials of convalescent plasma treatment, and 4 trials of hyperimmune globulin. These trials involved treatment of individuals either prophylactically or at different stages of infection including post-exposure prophylaxis, symptomatic infection, and hospitalisation. The level of antibody administered ranged from a 250 ml volume of convalescent plasma through to 8 grams of monoclonal antibodies. Data for analysis was extracted from the original publications including dose and antibody levels of antibody administered, disease stage and timing of administration, primary outcome of study and whether they reported on our prespecified outcomes of interest, which include protection against symptomatic infection, hospitalisation, need for invasive mechanical ventilation (IMV) and death (all-cause mortality at 30 days).Added value of this studyOur study included data across all 37 RCTs of passive antibody interventions for COVID-19 and aggregated the studies by the stage of infection at initiation of treatment. We found that prophylactic administration or treatment in earlier stages of infection had significantly higher effectiveness than later treatment. We also estimated the dose-response relationship between administered antibody dose and protection from progression from symptomatic ambulant COVID-19 to hospitalisation. We used this relationship to predict the efficacy of different monoclonal antibody treatment regimes against the Omicron subvariants BA.1, BA.2, and BA.4/5. We also used this dose-response relationship to estimate the maximal efficacy of monoclonal antibody therapy in the context of pre-existing endogenous neutralising antibodies.Implications of all the available evidenceThis work identifies that both prophylactic therapy and treatment in the early stages of symptomatic infection can achieve significant protection from infection or hospitalisation respectively. The dose-response relationship provides a quantitative means to predict the change in efficacy of different monoclonal antibodies against new variants and in semi-immune populations based on in vitro neutralisation data. We predict a number of existing monoclonal antibodies will be effective for preventing severe outcomes when administered early in BA.4/5 infections. It is likely that these therapies will provide little protection in individuals with high levels of endogenous neutralising antibodies, such as healthy individuals who have recently received a third dose of an mRNA vaccine.

Māori and Pacific peoples (MPP) in New Zealand (NZ) have poorer health outcomes than other ethnicities. However, this has not been clinically investigated in multiple myeloma (MM). Using data from the Australian and NZ Myeloma and Related Diseases Registry for all participating centers in NZ, we compared MPP demographics, clinical characteristics, diagnostics, treatment, and outcomes to non-MPP.MPP were defined as having ≥1 grandparent of this heritage. We tested ethnicity as a predictor of overall survival (OS) with multivariable Cox regression.Of 568 NZ patients with MM (September 2012 to April 2021) and ethnicity data, 138 were MPP. They were diagnosed younger than non-MPP (median age 63 [IQR: 57-72] vs. 70y [62-77], P.001). Obesity (53 vs. 27%, P.001), diabetes (24 vs. 8%, P.001), renal insufficiency (28 vs. 17%, P = .005), pulmonary disease (10 vs. 5%, P = .02) and FISH abnormalities (54 vs. 42%, P = .04) were more common in MPP, and a lower proportion received first-line drug therapy (88 vs. 94%, P = .03) and autologous stem cell transplant (ASCT) (age70y: 56 vs. 70%, P = .03). OS for MPP was shorter than non-MPP even after adjusting for age, comorbidities, disease stage, performance status, FISH abnormalities and treatment (HR 1.58 [1.04-2.39], P = .03).MPP with MM in NZ were younger, a greater proportion had comorbidities and FISH abnormalities at diagnosis, fewer received first-line treatment and/or ASCT, and they had poorer OS than non-MPP. Investigation of modifiable factors to improve outcomes and discern why MM occurs at a younger age in MPP is needed.

Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life-threatening condition.

It is uncertain whether the duration of red-cell storage affects mortality after transfusion among critically ill adults.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.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.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 .).

Optimal red cell transfusion thresholds in myelodysplastic syndrome are not established. In this survey of 110 Australasian haematologists' practice in myelodysplastic syndrome-related anaemia, 92% of respondents set transfusion thresholds, and would typically transfuse at a haemoglobin80 g/L aiming for a post-transfusion haemoglobin 90-100 g/L, reflecting a restrictive transfusion strategy. Higher thresholds were typically used for patients with cardiovascular disease or anaemia symptoms. These results will inform the design of clinical trials comparing transfusion thresholds.

Conflicting data exist about the impact of a monosomal karyotype (MK) on overall survival (OS) for patients with myelodysplastic syndromes (MDSs) and particularly for those with a complex karyotype (CK). This study was aimed at determining whether an MK is associated with OS independently of the number of cytogenetic abnormalities (CAs) in a population-based MDS cohort.Cancer registry data on incident MDS cases were linked with cytogenetic data and hospital administrative data from 2000 to 2010 for the Australian state of Victoria.Between 2000 and 2010, 1404 incident MDS cases with cytogenetic results were identified. A CK, defined as 3 or more abnormalities, was present in 126 (9%). A very complex karyotype (vCK), defined as 5 or more abnormalities, was present in 95 (7%). An MK was associated with worse OS in the whole cohort (median 6 vs 39 months, P 0.001) including those with a coexisting CK (6 vs 17 months, P 0.001) or vCK (6 vs 9 months, P = 0.02). After adjustments for the number of CAs, an MK remained independently associated with OS, although its effect size decreased with increasing cytogenetic complexity (hazard ratio for an MK, 4.81; 95% confidence interval, 3.08-7.52; hazard ratio for the number of CAs, 1.22; 95% confidence interval, 1.15-1.30; and hazard ratio for the interaction between an MK and CAs, 0.83; 95% confidence interval, 0.77-0.89).These results support the clinical utility of an MK as an independent predictor of adverse outcomes for MDS patients, even among CK and vCK groups, although its prognostic effect decreases with increasing cytogenetic complexity.

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.Data from the statewide Victorian Cancer Registry (VCR) and Victorian Admitted Episode Dataset (VAED, capturing all inpatient admissions), in Australia, were linked. Incidence rates were calculated based on VCR reported cases and using additional MDS cases identified in VAED. Differences between reported and nonreported cases were assessed. A multivariate capture-recapture method was used to estimate missed cases.Between 2003 and 2010, 2692 cases were reported to VCR and an additional 1562 cases were identified in VAED. Annual incidence rate for those aged 65 years and older based on VCR was 44 per 100,000 (95% confidence interval [CI] = 43-45 per 100,000) and 68 per 100,000 (95% CI = 67-70 per 100,000) using both data sets. Cases not reported to VCR were more likely to have had previous malignancies recorded in VAED (23% versus 19%, P = .003) and to require red cell transfusion (59% versus 54%, P = .003). Using the multivariate model, an estimated 1292 cases were missed by both data sources: the re-estimate was 5546 (95% CI = 5438-5655) MDS cases, with an annual incidence in those aged 65 or older of 103 per 100,000 (95% CI = 100-106).This study reports a higher incidence of MDS using 2 data sources from a large and well-defined population than reported using cancer registry notifications alone.

Estimating change in clinical demand for red blood cells (RBCs) from a disaster, as well as triaging introduced in response, is essential to plan effectively for a major blood shortage. We aimed to develop a RBC demand model to assess the impact of restriction policies on RBC use and patient outcomes.A compartmental dynamic model was developed in which patients require RBCs acutely (within 1 hr), urgently (24 hr), semiurgently (1-7 days), or nonurgently; outcomes included death or remaining at or transitioning to more or less urgent categories. A mathematical model was developed with transitions governed by differential equations and calibrated to a baseline scenario of adequate blood supply (using population-based hospital data sets, registries, and RBC issues). Distribution into urgency categories was based on a prospective study of 5132 randomly selected RBC units. Scenarios when the blood supply is limited compared to baseline were investigated. Transition rates between urgency categories under these scenarios were established by clinician survey.In the baseline 21-day scenario, patients requiring the most RBCs were other surgery (2162, 22%), medical anemia (1916, 12%), malignant hematology (1092, 16%), and gastrointestinal hemorrhage (1115, 8%). A policy of withholding RBCs for all nonurgent indications results in an estimated reduction of only 1007 (11.2%) RBC units and, if extended to semiurgent, a reduction of 2567 (28.5%) RBC units.Based on this model, restrictions that withhold transfusion from nonurgent patients have minimal impact on RBC demand and may not be sufficient to address changed demand and/or decreased supply during a prolonged disaster.

We investigated the incidence of myelodysplasia (MDS), its transfusion requirements, and complications of red blood cell (RBC) transfusion dependence (TD) using a hospitalization data set from a population of 5.3 million.This study was a retrospective cohort analysis of a population data set that captures diagnostic and procedure data on all hospitalizations from more than 300 hospitals within the Australian state of Victoria from 1998 to 2008.There were 3149 incident cases of MDS. The age-standardized incidence rate was higher than reported from local cancer registries (for 2007 9.6 per 100,000 [95% confidence interval {CI}, 9.2-10.0] vs. 4.8). Median age was 79 years, 56.3% were males, and 34.6% were TD-MDS. Overall number of hospitalizations with transfusion increased over the study period, but not median transfusion episodes per patient. TD-MDS was associated with new diagnoses of congestive heart failure (CHF; incident rate ratio [IRR], 1.92; 95% CI, 1.41-2.60), but not diabetes (IRR, 1.29; 95% CI, 0.54-3.04) or liver disease (IRR, 1.91; 95% CI, 0.63-5.78). TD-MDS was associated with bacterial (IRR, 1.75; 95% CI, 1.37-2.24) and fungal infections (IRR, 3.13; 95% CI, 1.70-5.75) and leukemia (relative risk [RR], 1.42; 95% CI, 1.07-1.88) and sepsis as cause of death (RR, 1.23; 95% CI, 1.03-1.47) but not CHF (RR, 0.97; 95% CI, 0.71-1.32).There was a higher incidence of MDS compared with that reported by cancer registries. Overall hospitalizations increased over the study period with no change in transfusion episodes per patient. There were more incident cases of CHF and infections in TD-MDS; however, CHF was not a more frequent cause of death.

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.

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.

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.We recruited premenopausal, eligible (nonanemic) female donors. Hb, ferritin, soluble transferrin receptor (sTfR), and hepcidin were measured, and the sTfR/(log)ferritin (sTfR-F) index was calculated. After 6 months, the donor database was reviewed and whether donors had returned and undergone successful donation was recorded.Of donors, 59 of 261(22.6%) were iron depleted (ferritin15 ng/mL). Iron-depleted donors had donated more often in the previous year, were younger, and had lower Hb. After a minimum of 6 months, 145 eligible donors had returned; of these 10 (6.9%) were deferred for anemia. Donors who developed anemia had significantly lower Hb, ferritin, and hepcidin and higher sTfR and sTfR-F at baseline. The area under the receiver operating characteristic curve for Hb as a predictor of deferral was 0.86, and for ferritin was 0.88. Hb of less than 130 g/L and ferritin of less than 10 ng/mL combined had sensitivity 80% and specificity 96% in predicting deferral.Screening with Hb and iron indices enables prediction of donors at risk of subsequent anemia and who would most benefit from prevention strategies.

Hospital transfusion laboratories collect information regarding blood transfusion and some registries gather clinical outcomes data without transfusion information, providing an opportunity to integrate these two sources to explore effects of transfusion on clinical outcomes. However, the use of laboratory information system (LIS) data for this purpose has not been validated previously.Validation of LIS data against individual patient records was undertaken at two major centers. Data regarding all transfusion episodes were analyzed over seven 24-hour periods.Data regarding 596 units were captured including 399 red blood cell (RBC), 95 platelet (PLT), 72 plasma, and 30 cryoprecipitate units. They were issued to: inpatient 221 (37.1%), intensive care 109 (18.3%), outpatient 95 (15.9%), operating theater 45 (7.6%), emergency department 27 (4.5%), and unrecorded 99 (16.6%). All products recorded by LIS as issued were documented as transfused to intended patients. Median time from issue to transfusion initiation could be calculated for 535 (89.8%) components: RBCs 16 minutes (95% confidence interval [CI], 15-18 min; interquartile range [IQR], 7-30 min), PLTs 20 minutes (95% CI, 15-22 min; IQR, 10-37 min), fresh-frozen plasma 33 minutes (95% CI, 14-83 min; IQR, 11-134 min), and cryoprecipitate 3 minutes (95% CI, -10 to 42 min; IQR, -15 to 116 min).Across a range of blood component types and destinations comparison of LIS data with clinical records demonstrated concordance. The difference between LIS timing data and patient clinical records reflects expected time to transport, check, and prepare transfusion but does not affect the validity of linkage for most research purposes. Linkage of clinical registries with LIS data can therefore provide robust information regarding individual patient transfusion. This enables analysis of joint data sets to determine the impact of transfusion on clinical outcomes.