Descriptive characteristics and in-hospital mortality of critically bleeding patients requiring massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry.

BACKGROUND AND OBJECTIVES: Critically bleeding patients requiring massive transfusion (MT) are clinically challenging, and limited data exist to support management decisions. This study describes patient characteristics, transfusion support and clinical outcomes from the Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR). MATERIALS AND METHODS: Retrospective, cohort study of all adult patients receiving MT (≥5 units red blood cells [RBC] in 4 h) at participating ANZ-MTR hospitals, 2011-2015. Mortality information was collected from the Australian National Death Index and NZ Ministry of Health. Associations between patient characteristics and outcomes were modelled using logistic regression. RESULTS: A total of 3560 MT cases were identified. For in-hospital deaths, cardiothoracic surgery was the most frequent bleeding context (24·5%) followed by trauma (18·3%). Age (OR = 1·03; 95% CI: 1·02-1·04), more comorbidities (OR = 1·14; 95% CI: 1·09-1·21), larger volume of RBC in first 24 h from MT onset (OR = 1·04; 95% CI: 1·02-1·06), higher platelet to RBC ratio at 4 h (OR = 2·76; 95% CI: 1·14-6·65) and higher activated partial thromboplastin time (OR = 1·02; 95% CI: 1·01-1·03) were associated with in-hospital mortality. CONCLUSION: Patients with more comorbidities, older age, traumatic or surgical bleeding or requiring more blood components had higher in-hospital mortality. These findings provide a basis to evaluate and monitor practice relating to optimal use of blood products, variation in transfusion practices and patient outcomes, and also enable benchmarking of hospital performance for management of MT in specific patient groups.

Evaluation of clinical coding data to determine causes of critical bleeding in patients receiving massive transfusion: a bi-national, multicentre, cross-sectional study.

OBJECTIVES: To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). BACKGROUND: Routinely collected data are increasingly being used to describe and evaluate transfusion practice. MATERIALS/METHODS: Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. RESULTS: A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70-0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40-0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). CONCLUSION: Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.

Improving outcomes for hospital patients with critical bleeding requiring massive transfusion: the Australian and New Zealand Massive Transfusion Registry study methodology.

BACKGROUND: The Australian and New Zealand (ANZ) Massive Transfusion (MT) Registry (MTR) has been established to improve the quality of care of patients with critical bleeding (CB) requiring MT (≥ 5 units red blood cells (RBC) over 4 h). The MTR is providing data to: (1) improve the evidence base for transfusion practice by systematically collecting data on transfusion practice and clinical outcomes; (2) monitor variations in practice and provide an opportunity for benchmarking, and feedback on practice/blood product use; (3) inform blood supply planning, inventory management and development of future clinical trials; and (4) measure and enhance translation of evidence into policy and patient blood management guidelines. The MTR commenced in 2011. At each participating site, all eligible patients aged ≥18 years with CB from any clinical context receiving MT are included using a waived consent model. Patient information and clinical coding, transfusion history, and laboratory test results are extracted for each patient's hospital admission at the episode level. RESULTS: Thirty-two hospitals have enrolled and 3566 MT patients have been identified across Australia and New Zealand between 2011 and 2015. The majority of CB contexts are surgical, followed by trauma and gastrointestinal haemorrhage. Validation studies have verified that the definition of MT used in the registry correctly identifies 94 % of CB events, and that the median time of transfusion for the majority of fresh products is the 'product event issue time' from the hospital blood bank plus 20 min. Data linkage between the MTR and mortality databases in Australia and New Zealand will allow comparisons of risk-adjusted mortality estimates across different bleeding contexts, and between countries. Data extracts will be examined to determine if there are differences in patient outcomes according to transfusion practice. The ratios of blood components (e.g. FFP:RBC) used in different types of critical bleeding will also be investigated. CONCLUSIONS: The MTR is generating data with the potential to have an impact on management and policy decision-making in CB and MT and provide benchmarking and monitoring tools for immediate application.

What factors contribute to hospital variation in obstetric transfusion rates?

BACKGROUND AND OBJECTIVES: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity. MATERIALS AND METHODS: Linked hospital discharge and birth data were used to identify births (n = 279 145) in hospitals with at least 10 deliveries per annum between 2008 and 2010 in New South Wales, Australia. To investigate transfusion rates, a series of random-effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed. RESULTS: Overall, the transfusion rate was 1.4% (hospital range 0.6-2.9) across 89 hospitals. Adjusting for maternal casemix reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type (range 1.1-2.0%). At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0.59, P = 0.01), but not with low Apgar scores (0.39, P = 0.08), or readmission rates (0.18, P = 0.29). CONCLUSION: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable; however, low transfusion rates were not associated with worse outcomes.

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion.

BACKGROUND AND OBJECTIVES: The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies. MATERIALS AND METHODS: Data were extracted on all patients who received red blood cell (RBC) transfusions in 2010 at three tertiary Australian hospitals. MT patients were identified according to three definitions: ≥10 units RBC in 24 h (10/24 h), ≥6 units RBC in 6 h (6/6 h) and ≥5 units RBC in 4 h (5/4 h). Clinical coding data were used to assign bleeding context. Data on in-hospital mortality were also extracted. RESULTS: Five hundred and forty-two patients met at least one MT definition, with 236 (44%) included by all definitions. The most inclusive definition was 5/4 h (508 patients, 94%) followed by 6/6 h (455 patients, 84%) and 10/24 h (251 patients, 46%). Importantly, 40-55% of most types of critical bleeding events and 82% of all obstetric haemorrhage cases were excluded by the 10/24 h definition. Patients who met both the 5/4 h and 10/24 h definitions were transfused more RBCs (19 vs. 8 median total RBC units; P < 0·001), had longer ventilation time (120 vs. 55 h; P < 0·001), median ICU (149 vs. 99 h; P < 0·001) and hospital length of stay (23 vs. 18 h; P = 0·006) and had a higher in-hospital mortality rate (23·3% vs. 16·4%; P = 0·050). CONCLUSION: The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort.

Clinicians as gatekeepers: what is the best route to optimal blood use?

Maintaining the supply of allogeneic blood has always been a challenge and its optimal use difficult to ensure and monitor. Increasingly, economic pressures and public perceptions have been driving decision making in delivery of sufficient and safe blood components of high quality. On the other hand, many of the assumed benefits of allogenic blood component therapy are being questioned, and the potential hazards of transfusion have been underestimated. Indeed, recent evidence suggests that in many clinical settings there are significant under-recognised hazards of transfusion in which benefit is difficult to confirm. This paper questions the current paradigm, in which there is excessive focus on the supply side of the blood transfusion chain rather than the clinical problem facing patients and clinicians. Blood transfusion should no longer be the default therapeutic decision when evidence for efficacy is lacking and there is clinical uncertainty. The appropriateness of transfusion practices will only improve, not by expecting clinicians to be gatekeepers of the blood supply, but with better patient blood management based on a sound understanding of pathophysiology and better evidence for transfusion efficacy. Evidence-based transfusion medicine should view a patient's own blood as a valuable and unique natural resource that should be conserved and managed appropriately. Altruistically donated allogeneic blood transfusion should only be used as therapy when there is evidence for potential benefit, there are no alternatives, a quality product is available and the risks are appropriately considered and balanced against the benefits.

Therapeutic apheresis.

During the last 30 years in vivo blood cell separation, generally referred to apheresis, has established a central role in both blood donor programmes and therapeutics. The technological advances in apheresis equipment has made procedures safer, faster and more effective. This article will review the use of apheresis in clinical medicine with emphasis on plasma exchange and peripheral blood stem cell collection. Plasma exchange now has a pivotal role in the management of a range of disorders, specially those with autoimmune pathogenesis. However, Plasma exchange should be practised as one component of an integrated and frequently multidisciplinary approach to management. The harvesting of allogeneic or autologous of peripheral blood haemopoietic stem cells is increased and it has become the principle indication for apheresis in many haematology units. A well coordinated protocol approach to this procedure is important if adequate haemopoietic stems cells are to be collected and safely cyropreserved. This requires successful cooperation between medical, nursing and scientific personnel.

Physiology and pathophysiology of blood volume regulation.

Adequate cardiac output and tissue perfusion is dependent on intravascular blood volume and its adequate return to the heart. Considering the overall functions of the cardiovascular system in ensuring appropriate flow to the peripheral microcirculation, it is not surprising that conflicts of interest may occur when an organism is exposed to stresses. Of particular importance are the stresses in which there are increased oxygen demands, decreased oxygen availability and concomitant requirements for thermoregulation. When there is depletion of intravascular blood volume, the splanchnic circulation is in effect an "autologous blood bank" for maintaining venous return until trans-capillary refill and haemodilution occurs. With the acute haematological stress response centralisation of blood, secondary contraction of the venous capacitance occurs, as seen with acute hypoxia. This results in overfilling of the heart, activation of atrial volume receptors, release of atrial natriuretic peptide and subsequent reduction of the plasma volume by rapid shifting of plasma into the lymphatic capacitance (via spleen) and transcapillary efflux throughout the circulation. In this overview the physiology and pathophysiology of blood volume, red cell mass and plasma volume regulation is reviewed.

Cytapheresis--the next 25 years: stem cell therapy.

Hemopoietic stem cell transplantation therapy has firmly established a role in the management of a range of malignant and nonmalignant disorders. Allogeneic bone marrow transplantation has been used as an adjunct in the treatment of acute leukemia with impressive results that have translated into long-term survival and cure. This experience has now extended to the management of other hematological malignancies and some solid tumors. With the ability to source hemopoietic stem cells from the peripheral blood by in vivo cytapheresis, there has been a rapid growth in the use of this form of therapy. The risks and benefits must be clearly appreciated and appropriate resources available with associated monitoring and quality assurance. There are few areas of medicine for which such close cooperation is necessary between medical, nursing, scientific, and allied health professionals to achieve successful outcomes. This paper addresses the logistical aspects of the provision of hemopoietic stem cell therapy in a routine clinical setting.

Cytapheresis: the first 25 years.

In vivo blood cell separator technology was originally developed in response to a perceived need for granulocytes for septic neutropenic patients. This impetus led to the development of a variety of cell separators which, paradoxically, ultimately have found their main applications in pheresis procedures other than granulocyte collection. In vivo blood cell separators are ideal for the removal of large numbers of normal or abnormal hemopoietic cells. Their early use in chronic myeloid leukemia demonstrated that leukapheresis could be used as definitive therapy for the disease. However, most hematological diseases in which the circulating malignant cells can be pheresed off have definitive and cost effective standard of care therapies, and cytapheresis is limited to specific circumstances. This paper reviews therapeutic cytapheresis and summarizes the current status of its limited specific indications.

What's new in clinical transfusion practice.

Although the Australian blood supply is among the safest in the world, homologous transfusion is not risk-free. In some circumstances, alternatives are available or being developed. Clinicians need to be aware of the risks, benefits and options in transfusion therapy and to fully inform patients of these.

Activated protein c resistance (APC) and inherited factor V (FV) mis-sense mutation in patients with venous and arterial thrombosis in a haematology clinic.

BACKGROUND: Inherited factor V (FV) mis-sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown. AIM: To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic. METHODS: Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis-sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay. RESULTS: Forty-five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis-sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non-European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV. CONCLUSION: This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e. young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.

Haematological parameters. What to order and why.

With the enormous range of laboratory investigations available from a modern haematology laboratory it is not surprising that a clinician may at times feel 'at sea' when finding a way through the diagnostic process. It is hoped that this 'haematological map' will help the busy clinician.