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Background: Extracorporeal life support (ECLS) is increasingly used worldwide over the past two decades and new indications are emerging, including extracorporeal cardiopulmonary resuscitation, trauma and COVID-19 cases. A frequent and remained feared complication is bleeding, and it is associated with high morbidity and mortality. However, trends of bleeding complications and outcomes have been poorly investigated. Method(s): Veno-venous (V-V) and veno-arterial (V-A) ECLS patients from the Extracorporeal Life Support Organization (ELSO) Registry database between 2000 and 2020 were included. Bleeding complication and mortality trends were analyzed. Bleeding complications included surgical site, cannulation site, gastrointestinal, pulmonary central nervous system and tamponade bleeding. Risk factors for bleeding complications were identified with multivariable analysis. Result(s): The analysis included 50.444 patients with single ECLS runs, 30.696 patients with V-A ECLS and 19.748 with V-V ECLS. Bleeding complications were reported in 13.534 patients (26.8%) and occurred more often in V-A ECLS compared to V-V ECLS patients (30.0% versus 21.9%). Bleeding patients showed lower hospital survival rates in both groups. Over the past twenty years bleeding complications showed a decreasing trend with a coefficient of -1.124 and -1.661 for V-V and V-A ECLS respectively. Surgical and cannulation site bleeding showed highest negative trend in both ECLS groups. Conclusion(s): The decrease in bleeding complications, especially cannulation and surgical site related bleeding, over the past two decades suggest improvement in anticoagulation management and possible equipment development. However, the persistent high rates of bleeding complications and association with mortality reinforces the need to understand bleeding complications more thoroughly during ECLS.

Background: Prophylactic immunoglobulin (Ig) replacement and prophylactic oral antibiotics (PA) are used to prevent infections in patients with haematological malignancies and acquired hypogammaglobulinemia. Ig has been shown to reduce infection risk, but is costly and in limited supply. PA have been shown to reduce infection risk in other patient populations and are less expensive, but have side-effects and can increase antimicrobial resistance rates. Guidelines and clinical practice vary internationally, with some recommending a trial of PA prior to commencing Ig replacement, and others omitting PA. The efficacy, safety and cost-effectiveness of Ig and PA have not been directly compared in a randomised controlled trial (RCT) in patients with acquired hypogammaglobulinemia secondary to haematological malignancies. Aim(s): To determine the feasibility of delivering PA as an alternative to Ig replacement in patients with haematological malignancies and acquired hypogammaglobulinemia. Method(s): Phase II, multicentre, feasibility RCT (ACTRN12616001723471). Eligible patients had acquired hypogammaglobulinemia due to a haematological malignancy, a history of recurrent or severe bacterial infections or an IgG level <4g/L (excluding paraprotein), and had a life expectancy more than 12 months. Exclusion criteria included prior allogeneic haematopoietic stem cell transplant and prior Ig replacement in the preceding 3 months. Patients were randomised to receive Ig (0.4g/kg IV every 4 weeks, modified to achieve an IgG trough level >= lower limit of reference range; or 0.1g/kg/week SC, modified to achieve an IgG trough level of >= lower limit of reference rage) or daily oral prophylactic antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg, with 100mg doxycycline as an alternative for hypersensitivity) for 12 months at a 1:2 ratio. Randomisation was stratified by site. Patients allocated to PA were allowed to cross over to Ig if they experienced a CTCAE >= Grade 3 infection.

Introduction: There is an increase in use of extracorporeal life support (ECLS) for cardiac support, with new indications emerging. Bleeding complications are the most frequent complications, associated with high morbidity and mortality. Despite the high frequency, the risk factors for bleeding complications remain poorly investigated. Method(s): To develop a prediction model for bleeding complications, adult patients included in the Extracorporeal Life Support Organization (ELSO) registry undergoing V-A ECLS between 2000 and 2020 were analyzed. The primary outcome was bleeding complications during V-A ECLS. Backward stepwise elimination in multivariable logistic regression analysis was used to develop the prediction model. The performance of the model was tested by ROC curves with AUC for discriminative ability and calibration plots. To detect overfitting of the model, internal validation was performed. Result(s): Single V-A ECLS runs were recorded in 28.767 adult patients, of which 29,0% developed bleeding complications. Sex, BMI, surgical cannulation, respiratory and hemodynamic variables prior to ECLS, the use of additional support devices, pre-ECLS interventions and different type of diagnosis were included in the prediction model. The model showed a fair predictive capability with an AUC of 0.66. Internal validation showed almost no overfitting of the model. An online calculator may simplify the use of the model. Conclusion(s): A multivariable model was developed and internally validated to calculate the risk for bleeding complications for adult patients receiving V-A ECLS. This model showed a favorabel predictive capability compared to the current literature. External validation is needed to confirm clinical use of this model.

Background: Extracorporeal life support (ECLS) is increasingly used worldwide over the past two decades and new indications are emerging, including extracorporeal cardiopulmonary resuscitation, trauma and COVID-19 cases. A frequent and remained feared complication is bleeding, and it is associated with high morbidity and mortality. However, trends of bleeding complications and outcomes have been poorly investigated. Method(s): Veno-venous (V-V) and veno-arterial (V-A) ECLS patients from the Extracorporeal Life Support Organization (ELSO) Registry database between 2000 and 2020 were included. Bleeding complication and mortality trends were analyzed. Bleeding complications included surgical site, cannulation site, gastrointestinal, pulmonary central nervous system and tamponade bleeding. Risk factors for bleeding complications were identified with multivariable analysis. Result(s): The analysis included 50.444 patients with single ECLS runs, 30.696 patients with V-A ECLS and 19.748 with V-V ECLS. Bleeding complications were reported in 13.534 patients (26.8%) and occurred more often in V-A ECLS compared to V-V ECLS patients (30.0% versus 21.9%). Bleeding patients showed lower hospital survival rates in both groups. Over the past twenty years bleeding complications showed a decreasing trend with a coefficient of -1.124 and -1.661 for V-V and V-A ECLS respectively. Surgical and cannulation site bleeding showed highest negative trend in both ECLS groups. Conclusion(s): The decrease in bleeding complications, especially cannulation and surgical site related bleeding, over the past two decades suggest improvement in anticoagulation management and possible equipment development. However, the persistent high rates of bleeding complications and association with mortality reinforces the need to understand bleeding complications more thoroughly during ECLS.

Background: Prophylactic immunoglobulin (Ig) replacement and prophylactic oral antibiotics (PA) are used to prevent infections in patients with haematological malignancies and acquired hypogammaglobulinemia. Ig has been shown to reduce infection risk, but is costly and in limited supply. PA have been shown to reduce infection risk in other patient populations and are less expensive, but have side-effects and can increase antimicrobial resistance rates. Guidelines and clinical practice vary internationally, with some recommending a trial of PA prior to commencing Ig replacement, and others omitting PA. The efficacy, safety and cost-effectiveness of Ig and PA have not been directly compared in a randomised controlled trial (RCT) in patients with acquired hypogammaglobulinemia secondary to haematological malignancies. Aim(s): To determine the feasibility of delivering PA as an alternative to Ig replacement in patients with haematological malignancies and acquired hypogammaglobulinemia. Method(s): Phase II, multicentre, feasibility RCT (ACTRN12616001723471). Eligible patients had acquired hypogammaglobulinemia due to a haematological malignancy, a history of recurrent or severe bacterial infections or an IgG level <4g/L (excluding paraprotein), and had a life expectancy more than 12 months. Exclusion criteria included prior allogeneic haematopoietic stem cell transplant and prior Ig replacement in the preceding 3 months. Patients were randomised to receive Ig (0.4g/kg IV every 4 weeks, modified to achieve an IgG trough level >= lower limit of reference range; or 0.1g/kg/week SC, modified to achieve an IgG trough level of >= lower limit of reference rage) or daily oral prophylactic antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg, with 100mg doxycycline as an alternative for hypersensitivity) for 12 months at a 1:2 ratio. Randomisation was stratified by site. Patients allocated to PA were allowed to cross over to Ig if they experienced a CTCAE >= Grade 3 infection.

Introduction: There is an increase in use of extracorporeal life support (ECLS) for cardiac support, with new indications emerging. Bleeding complications are the most frequent complications, associated with high morbidity and mortality. Despite the high frequency, the risk factors for bleeding complications remain poorly investigated. Method(s): To develop a prediction model for bleeding complications, adult patients included in the Extracorporeal Life Support Organization (ELSO) registry undergoing V-A ECLS between 2000 and 2020 were analyzed. The primary outcome was bleeding complications during V-A ECLS. Backward stepwise elimination in multivariable logistic regression analysis was used to develop the prediction model. The performance of the model was tested by ROC curves with AUC for discriminative ability and calibration plots. To detect overfitting of the model, internal validation was performed. Result(s): Single V-A ECLS runs were recorded in 28.767 adult patients, of which 29,0% developed bleeding complications. Sex, BMI, surgical cannulation, respiratory and hemodynamic variables prior to ECLS, the use of additional support devices, pre-ECLS interventions and different type of diagnosis were included in the prediction model. The model showed a fair predictive capability with an AUC of 0.66. Internal validation showed almost no overfitting of the model. An online calculator may simplify the use of the model. Conclusion(s): A multivariable model was developed and internally validated to calculate the risk for bleeding complications for adult patients receiving V-A ECLS. This model showed a favorabel predictive capability compared to the current literature. External validation is needed to confirm clinical use of this model.

Aim: To determine the feasibility of an electronic dataset comprising hospital laboratory data, transfusion data (any fresh or manufactured product) and clinical outcomes in Australian hospitals. To provide a 'issing link' in monitoring alignment of practice with, and impact of, Australian national patient blood management (PBM) policies and guidelines. Method(s): Using the platform of the Australian and New Zealand Massive Transfusion Registry, all data from adult patients transfused any blood product at participating sites for 2017, including laboratory (for transfusion and other laboratory records) and hospital information systems data (for patient demographics, co-morbidities, admission and clinical outcome data) were extracted. Data were securely sent, imported into the database and data linkage algorithms applied. Analyses were performed using Stata software. Result(s): Selected results from data analyses of the first pilot site are presented. During 2017, 5859 patients received at least 1 transfusion product during a total of 11 201 separate admissions; of these, 3407 (30%) were day-admissions. Length-of-stay (LoS) was >=10 days for 51% of admissions. 21% of hospital stays included ICU admission, of which 25% (577/2307 ICU admissions) were >10 days LoS in ICU. In-hospital mortality was 9.6% (565 deaths/5859 patients), of which 28 deaths (5% of 565 deaths) were LoS <1-day Emergency admissions. Transfused blood products included 24 766 RBC (red blood cells), 9365 PLT (platelets), 7701 FFP (fresh frozen plasma), 4422 Cryo (cryoprecipitate), 52 251 grams IVIg (intravenous immunoglobulin) and 6301 vials of Prothrombinex. Conclusion(s): This study demonstrates feasibility of a potential national dataset linking comprehensive information from readily available electronic hospital data sources on all patients transfused any type of blood product, including immunoglobulins and coagulation factor concentrates, with clinical outcomes data adjusted for demographics and c

Aim: Using Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR) describe Whole Blood (WB) use in massive transfusion (MT) (>=5 red blood cells (RBC) in any 4 h period) in NZ and compare transfusion requirements, laboratory parameters and patient outcomes for WB recipients (WB-R) with those receiving only RBC units (RBC-R). Method(s): All adult MT recipients between 2011 and 2018, at 4 NZ sites with access to WB, were included in the analysis. Result(s): Three hundred fifteen of 1947 (16.1%) MT recipients received >=1 WB unit. WB was most commonly used in vascular surgery (21%), trauma (17%), gastrointestinal (14%), cardiac surgery (11%). WB-R received a median of 2 (IQR 1, 2) WB units and commenced transfusion sooner relative to time of hospital admission than RBC-R. WB-R received fewer RBC (9 (6,16) vs 10 (7,15), P = 0.013), more fresh frozen plasma (FFP) (6 (2,11) vs 5 (2, 9), p < 0.001) and more recombinant FVIIa (P = 0.02) than RBC-R. There were no differences in fibrinogen concentrate, prothrombin complex or other fresh blood products given. In first 4-h of MT, WB-R had shorter APTT compared to RBC-R (42 (34, 60) vs 47 (36, 71) seconds; P = 0.01). Nadir haemoglobin, platelet count and fibrinogen for the 2 groups were similar. WB-R had higher in-hospital mortality (31.4% vs 25.3%, P = 0.024), but similar ICU length of stay and ventilation time. After adjusting for age, sex, number of RBC and FFP units, clinical context and hospital site there was no significant association between WB use and mortality (adjusted odds ratio WB Plasma Reduced 1.19 (95% CI 0.80-1.78) and WB Leucodepleted 1.42 (95% CI 0.94-2.15)).

Aim: Patients with haematologic malignancies are major recipients of blood products; however comprehensive Australian data about clinical outcomes of transfusion are limited. As part of a feasibility study to establish a national comprehensive dataset of all transfusions and their outcomes, we analysed transfusion data for adult haematology/oncology patients from the first pilot site. Method(s): Hospital electronic data on adult patients receiving any blood product (>=1 RBC [red blood cells], platelet, FFP [fresh frozen plasma], cryoprecipitate, or plasma derivative) during 2017 were imported, linked and analysed using the expanded platform of the Australian and New Zealand Massive Transfusion Registry. Data included laboratory (for transfusion and blood tests) and hospital information systems records (for patient demographics, co-morbidities, admission and clinical outcome data). Haematology/oncology patients were identified by ICD-10-AM diagnostic codes. Analyses were performed using Stata software. Result(s): Of 5859 transfused admitted patients, 767 (13%) were haematology/ oncology patients. Of these 38% were acute leukaemias, 25% myeloma, 15% NHL (non-Hodgkin lymphoma), 7% chronic leukaemias, and 15% MDS and other haematopoietic neoplasms. Patient median age was 66.7y, [IQR, 57, 74], and 58% were male. Haematology/oncology patients were 30% (3365/11201) of all admissions where a transfusion was performed; of which 56% were day-admissions. 61% of patients were admitted only once; 34% had 2-10 admissions and 5% had 11-100 admissions. They accounted for 33% RBCs, 69% platelets, 20% cryoprecipitate, 5% FFP and 13% IVIg (intravenous immunoglobulin; in grams) transfused. For outpatients receiving platelet transfusions, median [IQR] platelet count was 17 x109/L [10, 51]. Conclusion(s): Haematology/oncology patients represented 13% of all transfused patients, but required significant proportions of the transfusion product inventory, including 69% of all platelets, cons

Aim: To determine the feasibility of an electronic dataset comprising hospital laboratory data, transfusion data (any fresh or manufactured product) and clinical outcomes in Australian hospitals. To provide a 'issing link' in monitoring alignment of practice with, and impact of, Australian national patient blood management (PBM) policies and guidelines. Method(s): Using the platform of the Australian and New Zealand Massive Transfusion Registry, all data from adult patients transfused any blood product at participating sites for 2017, including laboratory (for transfusion and other laboratory records) and hospital information systems data (for patient demographics, co-morbidities, admission and clinical outcome data) were extracted. Data were securely sent, imported into the database and data linkage algorithms applied. Analyses were performed using Stata software. Result(s): Selected results from data analyses of the first pilot site are presented. During 2017, 5859 patients received at least 1 transfusion product during a total of 11 201 separate admissions; of these, 3407 (30%) were day-admissions. Length-of-stay (LoS) was >=10 days for 51% of admissions. 21% of hospital stays included ICU admission, of which 25% (577/2307 ICU admissions) were >10 days LoS in ICU. In-hospital mortality was 9.6% (565 deaths/5859 patients), of which 28 deaths (5% of 565 deaths) were LoS <1-day Emergency admissions. Transfused blood products included 24 766 RBC (red blood cells), 9365 PLT (platelets), 7701 FFP (fresh frozen plasma), 4422 Cryo (cryoprecipitate), 52 251 grams IVIg (intravenous immunoglobulin) and 6301 vials of Prothrombinex. Conclusion(s): This study demonstrates feasibility of a potential national dataset linking comprehensive information from readily available electronic hospital data sources on all patients transfused any type of blood product, including immunoglobulins and coagulation factor concentrates, with clinical outcomes data adjusted for demographics and c

Aim: Using Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR) describe Whole Blood (WB) use in massive transfusion (MT) (>=5 red blood cells (RBC) in any 4 h period) in NZ and compare transfusion requirements, laboratory parameters and patient outcomes for WB recipients (WB-R) with those receiving only RBC units (RBC-R). Method(s): All adult MT recipients between 2011 and 2018, at 4 NZ sites with access to WB, were included in the analysis. Result(s): Three hundred fifteen of 1947 (16.1%) MT recipients received >=1 WB unit. WB was most commonly used in vascular surgery (21%), trauma (17%), gastrointestinal (14%), cardiac surgery (11%). WB-R received a median of 2 (IQR 1, 2) WB units and commenced transfusion sooner relative to time of hospital admission than RBC-R. WB-R received fewer RBC (9 (6,16) vs 10 (7,15), P = 0.013), more fresh frozen plasma (FFP) (6 (2,11) vs 5 (2, 9), p < 0.001) and more recombinant FVIIa (P = 0.02) than RBC-R. There were no differences in fibrinogen concentrate, prothrombin complex or other fresh blood products given. In first 4-h of MT, WB-R had shorter APTT compared to RBC-R (42 (34, 60) vs 47 (36, 71) seconds; P = 0.01). Nadir haemoglobin, platelet count and fibrinogen for the 2 groups were similar. WB-R had higher in-hospital mortality (31.4% vs 25.3%, P = 0.024), but similar ICU length of stay and ventilation time. After adjusting for age, sex, number of RBC and FFP units, clinical context and hospital site there was no significant association between WB use and mortality (adjusted odds ratio WB Plasma Reduced 1.19 (95% CI 0.80-1.78) and WB Leucodepleted 1.42 (95% CI 0.94-2.15)).

Aim: Patients with haematologic malignancies are major recipients of blood products; however comprehensive Australian data about clinical outcomes of transfusion are limited. As part of a feasibility study to establish a national comprehensive dataset of all transfusions and their outcomes, we analysed transfusion data for adult haematology/oncology patients from the first pilot site. Method(s): Hospital electronic data on adult patients receiving any blood product (>=1 RBC [red blood cells], platelet, FFP [fresh frozen plasma], cryoprecipitate, or plasma derivative) during 2017 were imported, linked and analysed using the expanded platform of the Australian and New Zealand Massive Transfusion Registry. Data included laboratory (for transfusion and blood tests) and hospital information systems records (for patient demographics, co-morbidities, admission and clinical outcome data). Haematology/oncology patients were identified by ICD-10-AM diagnostic codes. Analyses were performed using Stata software. Result(s): Of 5859 transfused admitted patients, 767 (13%) were haematology/ oncology patients. Of these 38% were acute leukaemias, 25% myeloma, 15% NHL (non-Hodgkin lymphoma), 7% chronic leukaemias, and 15% MDS and other haematopoietic neoplasms. Patient median age was 66.7y, [IQR, 57, 74], and 58% were male. Haematology/oncology patients were 30% (3365/11201) of all admissions where a transfusion was performed; of which 56% were day-admissions. 61% of patients were admitted only once; 34% had 2-10 admissions and 5% had 11-100 admissions. They accounted for 33% RBCs, 69% platelets, 20% cryoprecipitate, 5% FFP and 13% IVIg (intravenous immunoglobulin; in grams) transfused. For outpatients receiving platelet transfusions, median [IQR] platelet count was 17 x109/L [10, 51]. Conclusion(s): Haematology/oncology patients represented 13% of all transfused patients, but required significant proportions of the transfusion product inventory, including 69% of all platelets, cons

Anaemia is a major public health issue, affecting 25% of the population worldwide according to the World Health Organization. Iron deficiency is responsible for approximately half of all cases globally, with other causes including anaemia of chronic disease, other nutritional deficiencies, haemoglobinopathies, renal impairment, malignancy and bone marrow disease. In the elderly, where anaemia is even more common, the cause is frequently multifactorial. Anaemia is associated with increased mortality, decreased cognitive and physical function, depressive symptoms and fatigue, particularly in older adults. Poor outcomes have also been reported in anaemic patients with underlying comorbidities such as cardiac and renal disease, and cancer. Within a hospital setting, anaemia is highly prevalent. Preoperative anaemia, affecting up to 30% of patients, is associated with poor clinical outcomes including higher in-hospital mortality, longer length of stay and higher ICU admission rates. Anaemia management requires a proactive and multi-faceted approach, typically involving a multi-disciplinary team in which the transfusion practitioner plays a vital role. This includes screening of high-risk patients and pre-admission clinics to identify and manage patients at high risk of peri-operative anaemia. Implementation of patient blood management (PBM) guideline recommendations has been shown to be effective to prevent and optimally manage anaemia within the community and hospital settings. The transfusion practitioner has key roles in the coordination, monitoring and auditing of PBM programs. Active patient involvement and engagement of all members of the multidisciplinary team, including primary care clinicians, are also key to enhance the success of such programs.

Background : t- PA can increase BBB permeability and trigger the infiltration of immune cells into the central nervous system. Few plasmin- dependent and - independent pathways participate in this phenomenon, for example, activation of Rho- Kinase 2 and platelet derived growth factor C, respectively. Since plasmin also possesses pro- inflammatory properties, including C3 and C5 convertase activity, we hypothesized that complement activation plays an additional role in this process. Aims : We aimed to evaluate the effect of complement inhibition on t- PA- and plasminogen (plg)- mediated opening of the BBB using an established in vitro model with C5 and C5a- receptor 1 (C5aR1) inhibitors. Methods : An in vitro model of the BBB was assembled on porous membranes of Transwell inserts as a co- culture system of human brain endothelial cells on the luminal surface and human immortalized astrocytes on the abluminal surface. The luminal compartment was stimulated with t- PA and plasminogen in the presence of PMX205 (non- competitive inhibitor of C5aR1), Avacopan (C5aR1 antagonist) or eculizumab (humanised monoclonal inhibitor of human C5). BBB permeability was assessed at both 4hr and 24hr post- stimulation by evaluation of fluorescent albumin passage from the luminal to the abluminal chambers over 1hr. Permeability changes were calculated relative to non- treated controls. Results : PMX205 and Avacopan decreased t- PA mediated increase in BBB permeability by almost 50%, at both the 4 and 24hr time points. Interestingly, our preliminary results indicate that eculizumab was without any significant effect. Conclusions : t- PA- and plasmin- mediated increase in BBB permeability is partly driven by C5a receptor activation. Inhibition of C5 or C5aR1 may have therapeutic implications in traumatic brain injury and stroke thrombolysis, where either endogenous or administered t- PA can compromise the BBB, leading to secondary insults.

Anaemia is a major public health issue, affecting 25% of the population worldwide according to the World Health Organization. Iron deficiency is responsible for approximately half of all cases globally, with other causes including anaemia of chronic disease, other nutritional deficiencies, haemoglobinopathies, renal impairment, malignancy and bone marrow disease. In the elderly, where anaemia is even more common, the cause is frequently multifactorial. Anaemia is associated with increased mortality, decreased cognitive and physical function, depressive symptoms and fatigue, particularly in older adults. Poor outcomes have also been reported in anaemic patients with underlying comorbidities such as cardiac and renal disease, and cancer. Within a hospital setting, anaemia is highly prevalent. Preoperative anaemia, affecting up to 30% of patients, is associated with poor clinical outcomes including higher in-hospital mortality, longer length of stay and higher ICU admission rates. Anaemia management requires a proactive and multi-faceted approach, typically involving a multi-disciplinary team in which the transfusion practitioner plays a vital role. This includes screening of high-risk patients and pre-admission clinics to identify and manage patients at high risk of peri-operative anaemia. Implementation of patient blood management (PBM) guideline recommendations has been shown to be effective to prevent and optimally manage anaemia within the community and hospital settings. The transfusion practitioner has key roles in the coordination, monitoring and auditing of PBM programs. Active patient involvement and engagement of all members of the multidisciplinary team, including primary care clinicians, are also key to enhance the success of such programs.

Background : t- PA can increase BBB permeability and trigger the infiltration of immune cells into the central nervous system. Few plasmin- dependent and - independent pathways participate in this phenomenon, for example, activation of Rho- Kinase 2 and platelet derived growth factor C, respectively. Since plasmin also possesses pro- inflammatory properties, including C3 and C5 convertase activity, we hypothesized that complement activation plays an additional role in this process. Aims : We aimed to evaluate the effect of complement inhibition on t- PA- and plasminogen (plg)- mediated opening of the BBB using an established in vitro model with C5 and C5a- receptor 1 (C5aR1) inhibitors. Methods : An in vitro model of the BBB was assembled on porous membranes of Transwell inserts as a co- culture system of human brain endothelial cells on the luminal surface and human immortalized astrocytes on the abluminal surface. The luminal compartment was stimulated with t- PA and plasminogen in the presence of PMX205 (non- competitive inhibitor of C5aR1), Avacopan (C5aR1 antagonist) or eculizumab (humanised monoclonal inhibitor of human C5). BBB permeability was assessed at both 4hr and 24hr post- stimulation by evaluation of fluorescent albumin passage from the luminal to the abluminal chambers over 1hr. Permeability changes were calculated relative to non- treated controls. Results : PMX205 and Avacopan decreased t- PA mediated increase in BBB permeability by almost 50%, at both the 4 and 24hr time points. Interestingly, our preliminary results indicate that eculizumab was without any significant effect. Conclusions : t- PA- and plasmin- mediated increase in BBB permeability is partly driven by C5a receptor activation. Inhibition of C5 or C5aR1 may have therapeutic implications in traumatic brain injury and stroke thrombolysis, where either endogenous or administered t- PA can compromise the BBB, leading to secondary insults.

Background: Massive obstetric haemorrhage (MOH) is defined as blood loss of >1000 ml during pregnancy and the puerperium with rising incidence and severity in the developed world. Dilutional coagulopathy, thrombocytopenia and hyperfib-rinogenaemia can perpetuate bleeding and require prompt correction in order to reduce mortality and morbidity. Aim(s): To better define current MOH transfusion management and clinical outcomes, including differences in cause of MOH. Method(s): We performed a bi-national, multi-centred, cohort study of women who received massive transfusion for MOH using the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). MOH was defined as >24 weeks gestation requiring >5 red blood cells (RBC) units within 4 h. Causes of bleeding were identi-fied using the International Classification of Diseases (ICD-10-AM) coding system. Result(s): 249 patients from 18 Australian and 5 New Zealand hospitals met the inclusion criteria. Modes of delivery were vaginal 115 (46%) or caesarean section (emergency 87 [35%]; elective 47 [19%]). Sixty-two percent occurred outside usual working hours defined as weekends as well as 6 pm-8 am on weekdays. Six patients were reported to develop an amniotic fluid embolism. Bleeding causes included obstetric trauma (n = 48, 19%), uterine atony/abnormal forces of labour (n = 56, 22%), placenta praevia (n = 51, 20%), other types of morbidly adherent placenta (n = 24, 9%) and other causes (n = 22, 8%). The majority (53%) had more than one and 48 patients had no documented cause. The median platelet count, APTT and INR were >75 9 10 99/L, <1.5 and <1.59 upper limit of normal, respectively at 4 and 24 h for all causes. Patients with placenta praevia and other types of morbidly adherent placenta had the highest median first fibrinogen levels (2.0 g/L [IQR 1.5-3.0] and 2.5 g/L [IQR 2.1-3.3] respectively). Ninety-five and 87% of women with prolonged nadir APTT/INR and nadir platelet count <50 9 109/L, respectively, receive

Background: Beta thalassaemia major is an inherited disorder of haemoglobin requiring life-long red blood cell (RBC) transfusion therapy. Information is required to understand the true costs of this support as part of overall management, and the cost-effectiveness of new treatments being developed for this condition. However, no current Australian or international data are available. Determining the true cost of trans-fusion requires a comprehensive investigation of the complex range of activities required in providing RBC support to a specific transfusion-dependent patient cohort, as various factors influence the cost (e.g. inpatient/outpatient setting), including laboratory, clinical and governance activities, and inputs required to deliver the service. Aim(s): To accurately determine the total cost of RBC transfusion support for adult transfusion-dependent thalassaemia patients at Monash Medical Centre (MMC), a thalassaemia treatment centre in Melbourne, Australia. Method(s): A time-driven activity-based costing (TD ABC) study of clinical, laboratory and administrative processes for RBC transfusions for transfusion-dependent adult thalassaemia patients at MMC was performed. Detailed process maps were developed for every procedure undertaken over 1 month (March 2017). Direct and indirect costs (personnel, consumables, equipment, clinical and testing procedures) were calculated, including costs of governance, managing long-term consequences of transfusion, and other complications. Detailed process maps and corresponding flowcharts were developed to provide a step-by-step description of the entire transfusion pathway including pre-transfusion phlebotomy, laboratory procedures, patient day admission for RBC administration, and treatments and processes directly related to the transfusion. Direct observations to verify process maps and timing of the processes were conducted. Expert opinion was obtained where processes were unable to be timed. All activities, resources

Background: Massive obstetric haemorrhage (MOH) is defined as blood loss of >1000 ml during pregnancy and the puerperium with rising incidence and severity in the developed world. Dilutional coagulopathy, thrombocytopenia and hyperfib-rinogenaemia can perpetuate bleeding and require prompt correction in order to reduce mortality and morbidity. Aim(s): To better define current MOH transfusion management and clinical outcomes, including differences in cause of MOH. Method(s): We performed a bi-national, multi-centred, cohort study of women who received massive transfusion for MOH using the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). MOH was defined as >24 weeks gestation requiring >5 red blood cells (RBC) units within 4 h. Causes of bleeding were identi-fied using the International Classification of Diseases (ICD-10-AM) coding system. Result(s): 249 patients from 18 Australian and 5 New Zealand hospitals met the inclusion criteria. Modes of delivery were vaginal 115 (46%) or caesarean section (emergency 87 [35%]; elective 47 [19%]). Sixty-two percent occurred outside usual working hours defined as weekends as well as 6 pm-8 am on weekdays. Six patients were reported to develop an amniotic fluid embolism. Bleeding causes included obstetric trauma (n = 48, 19%), uterine atony/abnormal forces of labour (n = 56, 22%), placenta praevia (n = 51, 20%), other types of morbidly adherent placenta (n = 24, 9%) and other causes (n = 22, 8%). The majority (53%) had more than one and 48 patients had no documented cause. The median platelet count, APTT and INR were >75 9 10 99/L, <1.5 and <1.59 upper limit of normal, respectively at 4 and 24 h for all causes. Patients with placenta praevia and other types of morbidly adherent placenta had the highest median first fibrinogen levels (2.0 g/L [IQR 1.5-3.0] and 2.5 g/L [IQR 2.1-3.3] respectively). Ninety-five and 87% of women with prolonged nadir APTT/INR and nadir platelet count <50 9 109/L, respectively, receive

Background: Beta thalassaemia major is an inherited disorder of haemoglobin requiring life-long red blood cell (RBC) transfusion therapy. Information is required to understand the true costs of this support as part of overall management, and the cost-effectiveness of new treatments being developed for this condition. However, no current Australian or international data are available. Determining the true cost of trans-fusion requires a comprehensive investigation of the complex range of activities required in providing RBC support to a specific transfusion-dependent patient cohort, as various factors influence the cost (e.g. inpatient/outpatient setting), including laboratory, clinical and governance activities, and inputs required to deliver the service. Aim(s): To accurately determine the total cost of RBC transfusion support for adult transfusion-dependent thalassaemia patients at Monash Medical Centre (MMC), a thalassaemia treatment centre in Melbourne, Australia. Method(s): A time-driven activity-based costing (TD ABC) study of clinical, laboratory and administrative processes for RBC transfusions for transfusion-dependent adult thalassaemia patients at MMC was performed. Detailed process maps were developed for every procedure undertaken over 1 month (March 2017). Direct and indirect costs (personnel, consumables, equipment, clinical and testing procedures) were calculated, including costs of governance, managing long-term consequences of transfusion, and other complications. Detailed process maps and corresponding flowcharts were developed to provide a step-by-step description of the entire transfusion pathway including pre-transfusion phlebotomy, laboratory procedures, patient day admission for RBC administration, and treatments and processes directly related to the transfusion. Direct observations to verify process maps and timing of the processes were conducted. Expert opinion was obtained where processes were unable to be timed. All activities, resources

Background The time to treatment initiation is determined by tumour burden in patients with follicular lymphoma (FL). The Groupe d'Etude des Lymphomes Folliculaires ('GELF') criteria, defined in the pre-rituximab era, are commonly used to assess tumour burden.2 Patients must meet >=1 of the following criteria to be considered "high" tumour burden according to GELF: any tumour mass >7 cm; >= 3 nodal sites (each >3 cm); B symptoms; splenomegaly; compression syndrome; pleural/peritoneal effusion; leukemic phase or cytopenias. Low tumour burden FL is often excluded from clinical trials, based on data from initial retrospective studies and later randomised trials, demonstrating no survival advantage with chemotherapy compared with observation alone. 1-3 Conversely, it is recommended those with high burden disease receive immediate therapy. The use of GELF in therapeutic decision-making outside of clinical trials is not well described. Methods Cases of newly diagnosed Grade 1-3a FL were retrospectively identified from the Australian Lymphoma and Related Diseases Registry (LaRDR), and 2 additional institutional databases from 2002-2019. Additional data was obtained from electronic hospital records. The primary aim of the study was to determine the utilisation of GELF criteria in guiding therapeutic decisions in FL. The secondary aims were to document frequency of GELF according to stage and treatment and to determine the impact of the number of GELF criteria on PFS. Survival analysis was calculated according to the Kaplan-Meier method. Results 385 cases were identified. Patient characteristics are in table 1. The median follow-up was 2 years (range 0.1-18) with 2-year PFS and OS of 89% (95% CI 85-92%) and 96% (95% CI 92-98%) respectively. 94 (24%) patients underwent a 'watch and wait' approach (W&W), 54 (14%) received radiotherapy alone and 237 (62%) received chemotherapy +/- radiotherapy. 118 (31%) patients had stage I/II disease at diagnosis, of these 36 (30%) underwent

Background The time to treatment initiation is determined by tumour burden in patients with follicular lymphoma (FL). The Groupe d'Etude des Lymphomes Folliculaires ('GELF') criteria, defined in the pre-rituximab era, are commonly used to assess tumour burden.2 Patients must meet >=1 of the following criteria to be considered "high" tumour burden according to GELF: any tumour mass >7 cm; >= 3 nodal sites (each >3 cm); B symptoms; splenomegaly; compression syndrome; pleural/peritoneal effusion; leukemic phase or cytopenias. Low tumour burden FL is often excluded from clinical trials, based on data from initial retrospective studies and later randomised trials, demonstrating no survival advantage with chemotherapy compared with observation alone. 1-3 Conversely, it is recommended those with high burden disease receive immediate therapy. The use of GELF in therapeutic decision-making outside of clinical trials is not well described. Methods Cases of newly diagnosed Grade 1-3a FL were retrospectively identified from the Australian Lymphoma and Related Diseases Registry (LaRDR), and 2 additional institutional databases from 2002-2019. Additional data was obtained from electronic hospital records. The primary aim of the study was to determine the utilisation of GELF criteria in guiding therapeutic decisions in FL. The secondary aims were to document frequency of GELF according to stage and treatment and to determine the impact of the number of GELF criteria on PFS. Survival analysis was calculated according to the Kaplan-Meier method. Results 385 cases were identified. Patient characteristics are in table 1. The median follow-up was 2 years (range 0.1-18) with 2-year PFS and OS of 89% (95% CI 85-92%) and 96% (95% CI 92-98%) respectively. 94 (24%) patients underwent a 'watch and wait' approach (W&W), 54 (14%) received radiotherapy alone and 237 (62%) received chemotherapy +/- radiotherapy. 118 (31%) patients had stage I/II disease at diagnosis, of these 36 (30%) underwent