A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia.

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015-2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05-6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01-1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients.

The burden of immune-mediated refractoriness to platelet transfusions in myelodysplastic syndromes.

Up to 65% of patients with myelodysplastic syndromes (MDS) have thrombocytopenia and require platelet (PLT) transfusion. The current standard of practice is to provide random- or single-donor PLT transfusion and manage PLT refractoriness (PLT-R) if and when it develops. This study assessed the prevalence and risk factors for immune-mediated PLT-R in patients in the South Australian (SA) MDS Registry. STUDY DESIGN AND METHODS: A retrospective analysis of MDS patients enrolled in the SA-MDS registry was performed. HLA data was analyzed from January 2003 to 30 June 2017 to ensure minimum follow-up of 2 years. RESULTS: During the study period, 341 of 681 (50%) MDS patients required at least one PLT transfusion, with 29 of 341 (9%) of all PLT transfusion patients requiring HLA-matched PLT transfusion for PLT-R. Of these 29 patients, 70% were females treated with disease-modifying therapies suggesting that these patients are at high risk of HLA alloimmunization. CONCLUSIONS: Immune-mediated PLT-R is common in MDS and can be expensive and difficult to manage once it occurs. Therefore, PLT transfusion practices should be optimized, especially for female MDS patients planned for disease-modifying therapies. This can help save time and streamline management, especially in the provision of PLT products for these patients, where the consequences of alloimmunization and PLT-R can be severe.

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome.

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.

Red alert - a new perspective on patterns of blood use in the South Australian public sector.

OBJECTIVES: In 2006 South Australia had a red cell issue rate, measured as product issues per 1000 population, 22.4% higher than the national average. A pilot study was undertaken to investigate the disparity in issue rates between SA and the national average with a secondary aim of establishing information on SA red cell use. METHODS: A linked electronic database was developed using clinical, epidemiological and red cell transfusion data within hospitals in the SA public sector. Aggregated red cell use across the SA public health sector was analysed by clinical variables such as Diagnosis Related Group (DRG), including specialty related groups (SRGs) and major diagnostic categories (MDCs). The DRGs that were associated with blood use were identified and applied to national hospital separations data in order to derive comparative blood utilisation rates for SA and Australia. RESULTS: Although blood issue and usage by population measure showed a significant difference of 22.4 and 22.0% respectively between SA and Australia, when measured against weighted separations the differences reduced to 7.4 and 7.1% respectively. CONCLUSION: This study showed the importance of analysing blood issues and utilisation on an activity adjusted basis rather than a raw per capita basis.