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Article: Fibrinogen, Coagulation, and Ageing.

Donkin, Rebecca / Fung, Yoke Lin / Singh, Indu

2023 Volume 102, Page(s) 313–342

Abstract: The World Health Organization estimates that the world's population over 60 years of age will nearly double in the next 30 years. This change imposes increasing demands on health and social services with increased disease burden in older people, ... ...

Abstract	The World Health Organization estimates that the world's population over 60 years of age will nearly double in the next 30 years. This change imposes increasing demands on health and social services with increased disease burden in older people, hereafter defined as people aged 60 years or more. An older population will have a greater incidence of cardiovascular disease partly due to higher levels of blood fibrinogen, increased levels of some coagulation factors, and increased platelet activity. These factors lead to a hypercoagulable state which can alter haemostasis, causing an imbalance in appropriate coagulation, which plays a crucial role in the development of cardiovascular diseases. These changes in haemostasis are not only affected by age but also by gender and the effects of hormones, or lack thereof in menopause for older females, ethnicity, other comorbidities, medication interactions, and overall health as we age. Another confounding factor is how we measure fibrinogen and coagulation through laboratory and point-of-care testing and how our decision-making on disease and treatment (including anticoagulation) is managed. It is known throughout life that in normal healthy individuals the levels of fibrinogen and coagulation factors change, however, reference intervals to guide diagnosis and management are based on only two life stages, paediatric, and adult ranges. There are no specific diagnostic guidelines based on reference intervals for an older population. How ageing relates to alterations in haemostasis and the impact of the disease will be discussed in this chapter. Along with the effect of anticoagulation, laboratory testing of fibrinogen and coagulation, future directions, and implications will be presented.
MeSH term(s)	Adult ; Aged ; Child ; Female ; Humans ; Middle Aged ; Aging/metabolism ; Anticoagulants ; Blood Coagulation/physiology ; Blood Coagulation Factors ; Fibrinogen/metabolism
Chemical Substances	Anticoagulants ; Blood Coagulation Factors ; Fibrinogen (9001-32-5)
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Review
ISSN	0306-0225 ; 0096-8757
ISSN	0306-0225 ; 0096-8757
DOI	10.1007/978-3-031-21410-3_12
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Article ; Online: Outcomes following perioperative red blood cell transfusion in patients undergoing elective major abdominal surgery: a systematic review and meta-analysis.

Morris, Fraser J D / Fung, Yoke-Lin / Craswell, Alison / Chew, Michelle S

British journal of anaesthesia

2023 Volume 131, Issue 6, Page(s) 1002–1013

Abstract: Background: Perioperative red blood cell transfusion is a double-edged sword for surgical patients. While transfusion of red cells can increase oxygen delivery by increasing haemoglobin levels, its impact on short- and long-term postoperative outcomes, ... ...

Abstract	Background: Perioperative red blood cell transfusion is a double-edged sword for surgical patients. While transfusion of red cells can increase oxygen delivery by increasing haemoglobin levels, its impact on short- and long-term postoperative outcomes, particularly in patients undergoing elective major abdominal surgery, is unclear. Methods: We conducted a systematic review and meta-analysis on the effect of perioperative blood transfusions on postoperative outcomes in elective major abdominal surgery. PubMed, Cochrane, and Scopus databases were searched for studies with data collected between January 1, 2000 and June 6, 2020. The primary outcome was short-term mortality, including all-cause 30-day or in-hospital mortality. Secondary outcomes included long-term all-cause mortality, any morbidity, infectious complications, overall survival, and recurrence-free survival. No randomised controlled trials were found. Thirty-nine observational studies were identified, of which 37 were included in the meta-analysis. Results: Perioperative blood transfusion was associated with short-term all-cause mortality (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.89-3.91, P<0.001), long-term all-cause mortality (hazard ratio 1.35, 95% CI 1.09-1.67, P=0.007), any morbidity (OR 2.18, 95% CI 1.81-2.64, P<0.001), and infectious complications (OR 1.90, 95% CI 1.60-2.26, P<0.001). Perioperative blood transfusion remained associated with short-term mortality in the sensitivity analysis after excluding studies that did not control for preoperative anaemia (OR 2.27, 95% CI 1.59-3.24, P<0.001). Conclusions: Perioperative blood transfusion in patients undergoing elective major abdominal surgery is associated with poorer short- and long-term postoperative outcomes. This highlights the need to implement patient blood management strategies to manage and preserve the patient's own blood and reduce the need for red blood cell transfusion. Trial registration: PROSPERO (CRD42021254360).
MeSH term(s)	Humans ; Erythrocyte Transfusion/adverse effects ; Anemia ; Blood Transfusion ; Elective Surgical Procedures ; Hospital Mortality
Language	English
Publishing date	2023-09-21
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2023.08.032
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Article ; Online: Investigating Age Appropriate Coagulation Reference Intervals to Support Patient Blood Management in the Elderly: A Verification Study.

Donkin, Rebecca / Fung, Yoke-Lin

Annals of clinical and laboratory science

2020 Volume 50, Issue 4, Page(s) 545–550

Abstract: Reference intervals are vital for interpreting coagulation results. Current interval ranges have no upper age limit, although there is evidence that coagulation function changes with age. This study compared coagulation results from healthy people aged > ... ...

Abstract	Reference intervals are vital for interpreting coagulation results. Current interval ranges have no upper age limit, although there is evidence that coagulation function changes with age. This study compared coagulation results from healthy people aged >60 years against adult reference intervals for routine clotting assays and thromboelastography (TEG) to determine if reference intervals are relevant to older adults.Samples from healthy blood donors aged >60 years (n=30 male, n=30 female) were tested by TEG® 6s, prothrombin time (PT), activated partial thromboplastin time (aPTT), and derived fibrinogen.All older donor-derived fibrinogen results were within the adult reference intervals, however levels were significantly higher in females. A proportion of TEG® 6s and aPTT results were not within the reference intervals. As populations around the world live longer, these findings question whether older adults require age specific coagulation reference intervals.
MeSH term(s)	Aged ; Aged, 80 and over ; Australia ; Blood Coagulation ; Blood Coagulation Factors/analysis ; Blood Coagulation Factors/standards ; Blood Coagulation Tests/methods ; Blood Transfusion ; Female ; Fibrinogen/metabolism ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time/methods ; Reference Values ; Thrombelastography/methods
Chemical Substances	Blood Coagulation Factors ; Fibrinogen (9001-32-5)
Language	English
Publishing date	2020-08-21
Publishing country	United States
Document type	Journal Article ; Validation Study
ZDB-ID	193092-8
ISSN	1550-8080 ; 0091-7370 ; 0095-8905
ISSN (online)	1550-8080
ISSN	0091-7370 ; 0095-8905
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Article ; Online: Unplanned blood use within 24 hours of emergency department presentation: A cohort study in an ageing population.

Simon, Geoff I / Craswell, Alison / Thom, Ogilvie / Fung, Yoke Lin

Emergency medicine Australasia : EMA

2021 Volume 34, Issue 2, Page(s) 244–251

Abstract: Objective: This research aims to elucidate drivers of blood use in an older population, with a focus on unplanned transfusions following ED presentation.: Methods: In a retrospective cohort study we examined 2015 data for ED presentations and blood ... ...

Abstract	Objective: This research aims to elucidate drivers of blood use in an older population, with a focus on unplanned transfusions following ED presentation. Methods: In a retrospective cohort study we examined 2015 data for ED presentations and blood use in two hospitals serving a population containing a high proportion (21%) of adults aged ≥65 years. Unplanned blood use was defined as any transfusion ≤24 h of presentation. Data were analysed by age, sex, Major Diagnostic Category, triage category and time to transfusion. Results: A total of 5294 blood components were transfused, comprising red cells (n = 3784), fresh frozen plasma (n = 657), platelets (n = 563) and cryoprecipitate (n = 290). Men aged ≥65 years were the highest users (40%, 2107 components). Unplanned transfusions accounted for 28% (n = 1057) of annual red cell use. Of 85 014 ED presentations, 494 (0.6%) were associated with unplanned red cell transfusion. Four Major Diagnostic Categories accounted for 81% (n = 853) of unplanned red cell use: gastrointestinal (n = 375), haematology (n = 267), trauma (n = 144) and cardiovascular (n = 67). Over one-fifth of unplanned transfusions (21%, n = 222 of 1057) were associated with ICD-10 codes for anaemia as a reason for presentation within the Haematology Major Diagnostic Category. Adults aged ≥65 years accounted for 62% of overall red cell use and 61% of transfusions ≤24 h of presentation. Odds of unplanned red cell transfusion increased with age, peaking at odds ratio 28.5 (95% confidence interval 14.2-57.4) in those aged 85 years and above. Conclusions: Unplanned blood use accounted for 28% of annual hospital blood consumption. Blood component use increased with age and was greatest in older men. A significant burden of anaemia treatment was identified by the ED.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aging ; Cohort Studies ; Emergency Service, Hospital ; Humans ; Male ; Retrospective Studies ; Triage
Language	English
Publishing date	2021-09-26
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2161824-0
ISSN	1742-6723 ; 1742-6731 ; 1035-6851
ISSN (online)	1742-6723
ISSN	1742-6731 ; 1035-6851
DOI	10.1111/1742-6723.13873
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Zs.A 5940: Show issues

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Article ; Online: Transfusion-related acute lung injury (TRALI): Potential pathways of development, strategies for prevention and treatment, and future research directions.

Tung, John-Paul / Chiaretti, Sara / Dean, Melinda M / Sultana, Annette J / Reade, Michael C / Fung, Yoke Lin

Blood reviews

2022 Volume 53, Page(s) 100926

Abstract: Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological ... ...

Abstract	Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological response modifiers (BRMs). Experimental evidence suggests at least six different pathways that antibody-mediated TRALI might follow: (i) two hit neutrophil activation; (ii) monocyte and neutrophil dependent; (iii) endothelial cell, neutrophil Fc receptor, platelet and neutrophil extracellular trap dependent; (iv) direct monocyte activation; (v) direct endothelial cell activation; and (vi) endothelial cell, complement and monocyte dependent. Two of these pathways (i and v) also apply to BRM-mediated TRALI. Different antibodies or BRMs might initiate different pathways. Even though six pathways are described, these might not be distinct, and might instead be interlinked or proceed concurrently. The different pathways converge upon reactive oxygen species release which damages pulmonary endothelium, precipitating fluid leakage and the clinical symptoms of TRALI. Additional pathways to the six described are likely to also contribute to TRALI pathogenesis, and this requires further investigation. This review also discusses evidence of protective mechanisms and their implications for clinical TRALI treatment. Finally, it suggests directions for future research to support the translation of these findings into strategies to prevent and treat clinical TRALI.
MeSH term(s)	Antibodies ; Blood Transfusion ; Humans ; Immunologic Factors ; Neutrophil Activation ; Neutrophils ; Transfusion Reaction ; Transfusion-Related Acute Lung Injury/etiology ; Transfusion-Related Acute Lung Injury/prevention & control
Chemical Substances	Antibodies ; Immunologic Factors
Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2021.100926
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Zs.A 2207: Show issues

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Article ; Online: Determining sex-specific preoperative haemoglobin levels associated with intraoperative red blood cell transfusion in cardiac surgery: a retrospective cohort study.

Cavalli, Leonardo B / Pearse, Bronwyn L / Craswell, Alison / Anstey, Christopher M / Naidoo, Rishendran / Rapchuk, Ivan L / Perel, Joanne / Hobson, Kylie / Wang, Mingzhong / Fung, Yoke-Lin

British journal of anaesthesia

2023 Volume 131, Issue 4, Page(s) 653–663

Abstract: Background: Anaemic cardiac surgery patients are at greater risk of intraoperative red blood cell transfusion. This study questions the application of the World Health Organization population-based anaemia thresholds (haemoglobin <120 g L: Methods: A ...

Abstract	Background: Anaemic cardiac surgery patients are at greater risk of intraoperative red blood cell transfusion. This study questions the application of the World Health Organization population-based anaemia thresholds (haemoglobin <120 g L Methods: A retrospective cohort study was conducted on adults ≥18 yr old undergoing cardiopulmonary bypass surgery. Logistic regression was applied to define sex-specific preoperative haemoglobin concentrations with reduced probability of intraoperative red blood cell transfusion for cardiac surgery patients. Results: Data on 4384 male and 1676 female patients were analysed. Binarily stratified multivariable logistic regression odds of receiving intraoperative red blood cell transfusion increased in cardiac surgery patients >45 yr old (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.33-2.55), surgery urgency <30 days (OR 2.03; 95% CI 1.66-2.48), combined coronary artery bypass grafting and valve surgery, or other surgery types (OR 2.24; 95% CI 1.87-2.67), and female sex (OR 1.92; 95% CI 1.62-2.28). The odds decreased by 8.4% with each 1 g L Conclusions: The World Health Organization female anaemia threshold of haemoglobin <120 g L
MeSH term(s)	Adult ; Humans ; Female ; Male ; Erythrocyte Transfusion ; Retrospective Studies ; Cardiac Surgical Procedures ; Coronary Artery Bypass ; Probability
Language	English
Publishing date	2023-08-29
Publishing country	England
Document type	Journal Article
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2023.06.062
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Article ; Online: Authors' reply to comment Blood transfusion strategies in elderly patients.

Simon, Geoff I / Craswell, Alison / Thom, Ogilvie / Fung, Yoke Lin

The Lancet. Haematology

2017 Volume 4, Issue 11, Page(s) e508

MeSH term(s)	Aged ; Blood Transfusion ; Humans
Language	English
Publishing date	2017-09-11
Publishing country	England
Document type	Letter ; Comment
ISSN	2352-3026
ISSN (online)	2352-3026
DOI	10.1016/S2352-3026(17)30172-2
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Article ; Online: Blood management in hip fractures; are we leaving it too late? A retrospective observational study.

Puckeridge, Gillian / Terblanche, Morne / Wallis, Marianne / Fung, Yoke Lin

BMC geriatrics

2019 Volume 19, Issue 1, Page(s) 79

Abstract: Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its ... ...

Abstract	Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its progression prior to surgery in this cohort. We aimed to measure the prevalence of anaemia on admission in older persons who sustain a hip fracture, identify if anaemia develops or progresses prior to surgery, and to report associations with outcome. Methods: A retrospective, observational study was undertaken in a regional hospital. All patients aged 60 and over, admitted with a primary hip fracture resulting from a simple fall, in the 12 months of 2014 were included. The World Health Organization (WHO) definition of anaemia was used. Pathology databases and clinical records were reviewed to collect data. Repeated measures ANOVA's were used to quantify the progression of anaemia prior to surgery, and Chi square test were used to report associations with outcome variables. Results: Two hundred sixty-one patients were identified, median age was 81 years. There were twice as many females as males and just over half the sample had extracapsular fractures. Anaemia was present on admission in 45% (n = 117), highest incidence of anaemia occurred in males 52.0% (n = 39), extracapsular fractures 41.9% (n = 78) and those aged over 80 years 49.7% (n = 91). Progression of anaemia prior to surgery was significant in all groups (p < 0.05), with the greatest reduction seen in extracapsular fractures. Pre-surgery reduction in Hb was recorded in 82.3% of patients between admission and day 1, and in 71.4% between admission and day 2. There was significant association between anaemia on admission and PRBC transfusion (p < 0.05), in hospital mortality (p < 0.05) however no association with the use of antiplatelet or anticoagulant medication, nor LOS. Conclusions: The findings demonstrate that pre-surgical anaemia in older hip fracture patients is associated with a PRBC transfusion and increased hospital mortality. Importantly, it also identified that patients continue to bleed after admission, leading to the development of or worsening anaemia. Thus, identification anaemia in the pre-surgical period provides an opportunity for treatment to avoid transfusions and improve patient outcomes.
MeSH term(s)	Accidental Falls ; Aged ; Aged, 80 and over ; Anemia/diagnosis ; Anemia/mortality ; Anemia/therapy ; Cohort Studies ; Erythrocyte Transfusion/methods ; Erythrocyte Transfusion/mortality ; Female ; Hip Fractures/mortality ; Hip Fractures/surgery ; Hospital Mortality ; Humans ; Male ; Postoperative Care/methods ; Postoperative Care/mortality ; Prevalence ; Queensland/epidemiology ; Retrospective Studies
Language	English
Publishing date	2019-03-12
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-019-1099-x
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Article ; Online: Ovine red cell concentrates for transfusion research - is the storage lesion comparable to human red cell concentrates?

Simonova, Gabriela / Wellburn, Rebecca / Fung, Yoke Lin / Fraser, John F / Tung, John-Paul

Vox sanguinis

2020 Volume 116, Issue 5, Page(s) 524–532

Abstract: Background and objectives: Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell ... ...

Abstract	Background and objectives: Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings. Materials and methods: OvRCCs (n = 5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n = 5), were stored at 2-6°C for 42 days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis. Results: Ovine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs. Conclusion: This study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings.
MeSH term(s)	Animals ; Blood Preservation/methods ; Blood Preservation/standards ; Blood Transfusion/methods ; Blood Transfusion/standards ; Disease Models, Animal ; Erythrocytes/metabolism ; Humans ; Sheep/blood
Language	English
Publishing date	2020-10-26
Publishing country	England
Document type	Journal Article
ZDB-ID	80313-3
ISSN	1423-0410 ; 0042-9007
ISSN (online)	1423-0410
ISSN	0042-9007
DOI	10.1111/vox.13020
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Article: A retrospective explanatory case study of the implementation of a bleeding management quality initiative, in an Australian cardiac surgery unit.

Pearse, Bronwyn Louise / Rickard, Claire M / Keogh, Samantha / Lin Fung, Yoke

Australian critical care : official journal of the Confederation of Australian Critical Care Nurses

2018 Volume 32, Issue 2, Page(s) 92–99

Abstract: Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles ... ...

Abstract	Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; "How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?" Methods: A retrospective explanatory case study design was chosen to explore the quality initiative. Analysis of the evidence was reviewed through phases of the 'Knowledgeto Action' planned change model. Data was derived from: (1) document analysis, (2) direct observation of the local environment, (3) clinical narratives from interviews, and analysed with a triangulation approach. The study period extended from 10/2011 to 6/2013. Results: Results demonstrated the complexity of changing practice, as well as the significant amount of dedicated time and effort required to support individual, department and system wide change. Results suggest that while many clinicians were aware of the potential to apply improved practice, numerous barriers and challenges needed to be overcome to implement change across multiple disciplines and departments. Conclusions: The key successful components of the QI were revealed through the case study analysis as: (1) an appropriately skilled project manager to facilitate the implementation process; (2) tools to support changes in workflow and decision making including a bleeding management treatment algorithm with POCCTs; (3) strong clinical leadership from the multidisciplinary team and; (4) the evolution of the project manager position into a perpetual clinical position to support sustainability.
MeSH term(s)	Australia ; Cardiac Surgical Procedures ; Hemorrhage/prevention & control ; Humans ; Organizational Case Studies ; Quality Improvement ; Retrospective Studies
Language	English
Publishing date	2018-03-09
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1159493-7
ISSN	1878-1721 ; 1036-7314
ISSN (online)	1878-1721
ISSN	1036-7314
DOI	10.1016/j.aucc.2018.01.001
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