Search

Background and objectives Studies have shown granulocyte transfusions (GTXs) may be beneficial in neutropaenic patients with severe systemic infections. New Zealand Blood Service has a policy for provision of granulocytes to New Zealand's District Health Boards. We set out to explore utilization of therapeutic granulocyte infusions in New Zealand. Materials and methods Patients who received GTXs in the 16-year period between 2000 and 2016 were identified by the New Zealand electronic blood management system, eProgesa. Information pertaining to recipient demographics, disease-related factors, methods of granulocyte collection and clinical outcomes was obtained by the review of electronic transfusion and clinical records. Results Forty-five septic patients received granulocyte support for a total of 263 days. The median age of the recipients was 16 (range 0-74) years. Seventy-nine percent of the recipients had an underlying haematological malignancy with 50% having acute leukaemia. The median neutrophil count on the last day of GTX was 0.02 × 109 /L (range 0-16.32). Sixty-three percent (27/43 patients with available data) had persisting severe neutropaenia when the GTXs were stopped. The median duration of support was 3 (range 1-32) days. Forty-six percent of granulocyte collections were performed via apheresis. Of the 44 patients, for whom survival outcome was available, 18 (41%) survived the acute illness. Conclusion GTXs were infrequently used, most commonly in the setting of an underlying haematological malignancy. This may be explained by the current weak evidence base supporting this therapeutic modality. Procuring a sufficiently large dose of granulocytes for infusion remains an issue for adult recipients.

IntroductionCryopreservation at −80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries.Methods and analysisCLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change in clinical practice. Cost-effectiveness analyses will be incorporated into each study such that, should clinical non-inferiority compared with standard care be demonstrated, the hospitals in each country that would benefit most from changing to a cryopreserved platelet blood bank will be known.Ethics and disseminationCLIP-II was approved by the Austin Health Human Research Ethics Committee (HREC/54406/Austin-2019) and by the Australian Red Cross Lifeblood Ethics Committee (2019#23). CLIPNZ-II was approved by the New Zealand Southern Health and Disability Ethics Committee (21/STH/66). Eligible patients are approached for informed consent at least 1 day prior to surgery. There is no provision for consent provided by a substitute decision-maker. The results of the two trials will be submitted separately for publication in peer-reviewed journals.Trial registration numbersNCT03991481and ACTRN12621000271808.

Background and objectives Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. Materials and methods This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. Results Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 103 /μl vs. 157 × 103 /μl, median difference 39.5 ×103 /μl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. Conclusion This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.

New Zealand has a strategy of eliminating SARS-CoV-2 that has resulted in a low incidence of reported coronavirus-19 disease (COVID-19). The aim of this study was to describe the spread of SARS-CoV-2 in New Zealand via a nationwide serosurvey of blood donors. Samples (n = 9806) were collected over a month-long period (3 December 2020–6 January 2021) from donors aged 16–88 years. The sample population was geographically spread, covering 16 of 20 district health board regions. A series of Spike-based immunoassays were utilised, and the serological testing algorithm was optimised for specificity given New Zealand is a low prevalence setting. Eighteen samples were seropositive for SARS-CoV-2 antibodies, six of which were retrospectively matched to previously confirmed COVID-19 cases. A further four were from donors that travelled to settings with a high risk of SARS-CoV-2 exposure, suggesting likely infection outside New Zealand. The remaining eight seropositive samples were from seven different district health regions for a true seroprevalence estimate, adjusted for test sensitivity and specificity, of 0.103% (95% confidence interval, 0.09–0.12%). The very low seroprevalence is consistent with limited undetected community transmission and provides robust, serological evidence to support New Zealand's successful elimination strategy for COVID-19.

Objectives Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS‐CoV‐2 antibodies. This study explored antibody responses in recovered COVID‐19 patients in a setting where the probability of re‐exposure is effectively nil, owing to New Zealand's successful elimination strategy. Methods A triplex bead‐based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS‐CoV‐2 was developed. After establishing baseline levels with pre‐pandemic control sera (n = 113), samples from PCR‐confirmed COVID‐19 patients with mild–moderate disease (n = 189) collected up to 8 months post‐infection were examined. The relationship between antigen‐specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE‐2 interaction. Results While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4–8 months post‐infection. Anti‐RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti‐RBD IgG was demonstrated. Conclusion Antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting., This study shows that antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in New Zealand. The figure was created with BioRender.com.

ObjectivesCirculating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealand’s successful elimination strategy.MethodsA triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3, IgG4) responses against Nucleocapsid (N) protein, Receptor Binding Domain (RBD) and Spike (S) protein of SARS-CoV-2 was developed. After establishing baseline levels with pre-pandemic control sera (n=113), samples from PCR-confirmed COVID-19 patients with mild-moderate disease (n=189) collected up to eight months post-infection were examined. The relationship between antigen-specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE-2 interaction.ResultsWhile most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4-8 months post-infection. Anti-RBD antibodies were strongly correlated with NAbs at all time points (Pearson’s r ≥ 0.87) and feasibility of using finger prick sampling to accurately measure anti-RBD IgG was demonstrated.ConclusionAntibodies to SARS-CoV-2 persist for up to eight months following mild to moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.

BACKGROUND AND OBJECTIVES Analyser blockage due to gel formation by paraproteins leading to invalid results is a rare problem in viral nucleic acid testing (NAT) at New Zealand Blood Service (NZBS) despite many blood samples tested without problems from individuals with known paraproteins. This study aimed to identify common factors in samples causing blockages. METHOD Retrospective data were gathered on blood samples known to have blocked analysers at NZBS testing sites. Patients with plasma cell dyscrasia undergoing haematopoietic stem cell (HSC) harvest formed the comparator arm. These patients were identified from registry data of individuals undergoing autologous stem cell transplantation at Auckland City Hospital between 2013 and 2017. RESULTS Four individuals were identified as having blocked analysers between 2010 and 2018. A total of 184 HSC transplant patients were identified, with contemporaneous paraprotein levels available for 177 (96%). Patients with intact immunoglobulin subtypes (134, 73%) were further analysed. Of these, 119 patients (65%) also had total protein and globulin levels available. Mean paraprotein (37.5 g/l), total protein (95.3 g/l), globulin levels (51.5 g/l) and proportion of lambda subtype (75%) were higher in the blocker group compared with non-blocking comparators (4.7 g/l, 66.8 g/l, 27.7 g/l, 36.6% respectively) (P = 0·03, 0·02, 0·007, 0·12). The highest paraprotein and total protein levels from the non-blocking cohort overlapped with the lowest of the blocker group. DISCUSSION High protein levels (paraprotein >20 g/l, total protein >75 g/l) and a trend towards lambda subtype were associated with NAT analyser blockage. The overlap with non-blocking donor samples suggests factors in addition to protein quantity that are also important.

International audience

BACKGROUND Cryopreserved platelet (PLT) components stored at −80°C in 5% to 6% dimethyl sulfoxide (DMSO) demonstrate enhanced hemostatic activity. Alterations in PLT surface glycoprotein expression and release of procoagulant microparticles during the freeze/thaw cycle result in PLT activation. Nothing is known of the effect of gamma irradiation on the in vitro quality of reconstituted cryopreserved PLTs. STUDY DESIGN AND METHODS Gamma-irradiated (25-50 Gy) buffy coat–derived PLT components were either stored at room temperature for 7 days (the current expiry in New Zealand) or cryopreserved at −80°C using 5% to 6% DMSO. Cryopreserved PLTs were thawed at 37°C and reconstituted in ABO-identical plasma or PAS-E and compared to Day 7 gamma-irradiated liquid-stored PLTs. In vitro assays were performed to assess glycoprotein expression, PLT functionality and soluble cytokine release. RESULTS Cryopreserved PLTs after thawing and reconstitution in ABO-matched plasma or PAS-E displayed differing recoveries (82.7 and 75.9%, respectively). Key expression levels of glycoproteins GPIbα (CD42b) and GPIIb (CD41a) were reduced. Cryopreserved PLTs retained the ability to form an effective functional clot, while showing accelerated initiation of clot formation (R-time) compared to Day 7 gamma-irradiated liquid-stored PLTs. CONCLUSION Gamma-irradiated buffy coat–derived liquid-stored and cryopreserved PLTs have distinctly differing phenotypes. Cryopreserved PLTs reconstituted in ABO plasma have enhanced clot strength driven by coagulation factors and fibrinogen levels not present in PAS-E. Irradiated cryopreserved PLTs maintain a similar in vitro quality profile and hemostatic behavior to previously published, nonirradiated cryopreserved PLTs.

Background The low, fluctuating levels of DNA characteristic of occult hepatitis B infection make its detection by nucleic acid testing (NAT) a challenge. Methods Four year’s routine use of the Ultrio and Ultrio Plus assays in blood donations in New Zealand was analysed. Results 0·09% of donations tested with Ultrio and Ultrio Plus assays showed reactivity in the multiplex assay, but non-reactivity in all three discriminatory assays and relevant mandatory serological assays (anti-HIV, anti-HCV, HBsAg). These donations were more likely to be anti-HBc reactive (Ultrio, 13%; Ultrio Plus, 57%; random donors, 6·8%). Thirty-four per cent of these anti-HBc-reactive donations were also reactive in either an alternate NAT assay or on repeat multiplex testing. Thirteen per cent of the donors of the discriminatory-negative, anti-HBc-reactive donations who had given other Ultrio- or Ultrio Plus-tested donations had at least one other multiplex reactive donation. Conclusion These findings suggest that their HBV DNA levels are around the assay’s limit of detection, that false reactivity cannot be presumed when a donor fails to discriminate and that caution should be applied when deciding whether to continue accepting donations from such donors.

To identify what diagnoses account for the utilisation of intravenous immunoglobulin (IVIG) in New Zealand (NZ), to establish regional differences in prescribing patterns, and to audit the appropriateness of its use in a subset of patients.We accessed NZ Blood Service and NZ Health Information Service data to retrospectively determine the quantities of IVIG issued by each District Health Board (DHB) during 2004 and the diagnoses associated with each treatment episode. DHB-of-domicile data was used to explore the influence of cross boundary flow of patients. In a further prospective audit performed over 6 months we collected data on all utilisation of IVIG in eight DHB. The indications for IVIG were checked for compliance with the Australian Health Minister's Advisory Council (AHMAC) and Auckland District Health Board (ADHB) guidelines.Retrospective audit--The rates at which IVIG was prescribed varied 11-fold across the different DHB, from 100.5 g/1000 population in Capital and Coast DHB to 8.8 g/1000 in Nelson-Marlborough DHB. With cross-boundary flow analysis, the rates at which the residents of different DHB received IVIG (from any DHB) varied 10-fold. The Auckland DHB (and to a lesser extent some other DHB) provided substantial amounts of IVIG to treat patients resident in other DHB. Eccentric patterns of utilisation (e.g. obstetric) were found in some regions. Prospective audit--We captured 466 treatment episodes. Primary antibody deficiency was by far the most frequent diagnosis. Five diagnoses accounted for 69% of the total IVIG utilisation. 80.6% of the diagnoses were in AHMAC category 1 (convincing evidence of benefit) and 71.5% were approved diagnoses in the ADHB guidelines. Compliance with the two sets of guidelines varied significantly across the different DHB.A limited set of disorders accounts for most of the IVIG prescribed in NZ. The wide variation in the patterns of utilisation in different regions is probably due to a range of factors and could usefully be studied further. There is almost certainly under- and over-utilisation in some regions for certain diagnostic categories. Up-to-date, evidence-based guidelines and a rigorous authorisation process have the potential to promote appropriate utilisation.

Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.