Heidi Doughty

Hyperhemolytic transfusion reaction in sickle cell disease

BACKGROUND: An atypical form of life‐threatening hemolytic transfusion reaction (HTR) in patients with sickle cell disease (SCD) has been well described in the literature. Continuation of blood transfusion may be lethal, as it can further exacerbate hemolysis. The pathophysiologic mechanism of HTR is not well understood.

Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps.

ABSTRACT The Trauma Hemostasis and Oxygenation Research Network held its third annual Remote Damage Control Resuscitation Symposium in June 2013 in Bergen, Norway. The Trauma Hemostasis and Oxygenation Research Network is a multidisciplinary group of investigators with a common interest in improving outcomes and safety in patients with severe traumatic injury. The network’s mission is to reduce the risk of morbidity and mortality from traumatic hemorrhagic shock, in the prehospital phase of resuscitation through research, education, and training. The concept of remote damage control resuscitation is in its infancy, and there is a significant amount of work that needs to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical in these patients. If shock and coagulopathy can be rapidly identified and minimized before hospital admission, this will very likely reduce morbidity and mortality. This position statement begins to standardize the terms used, provides an acceptable range of therapeutic options, and identifies the major knowledge gaps in the field.

Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial

BACKGROUND Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality. METHODS This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21). RESULTS 85% (95% CI: 69-100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57-76) compared with 108 min (67-147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre(-1) at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14). CONCLUSIONS Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes. TRIAL REGISTRY NUMBER ISRCTN55509212.

LOW TITER GROUP O WHOLE BLOOD IN EMERGENCY SITUATIONS

ABSTRACT In past and ongoing military conflicts, the use of whole blood (WB) as a resuscitative product to treat trauma-induced shock and coagulopathy has been widely accepted as an alternative when availability of a balanced component-based transfusion strategy is restricted or lacking. In previous military conflicts, ABO group O blood from donors with low titers of anti-A/B blood group antibodies was favored. Now, several policies demand the exclusive use of ABO group–specific WB. In this short review, we argue that the overall risks, dangers, and consequences of “the ABO group–specific approach,” in emergencies, make the use of universal group O WB from donors with low titers of anti-A/B safer. Generally, risks with ABO group–specific transfusions are associated with in vivo destruction of the red blood cells transfused. The risk with group O WB is from the plasma transfused to ABO-incompatible patients. In the civilian setting, the risk of clinical hemolytic transfusion reactions (HTRs) due to ABO group–specific red blood cell transfusions is relatively low (approximately 1:80,000), but the consequences are frequently severe. Civilian risk of HTRs due to plasma incompatible transfusions, using titered donors, is approximately 1:120,000 but usually of mild to moderate severity. Emergency settings are often chaotic and resource limited, factors well known to increase the potential for human errors. Using ABO group–specific WB in emergencies may delay treatment because of needed ABO typing, increase the risk of clinical HTRs, and increase the severity of these reactions as well as increase the danger of underresuscitation due to lack of some ABO groups. When the clinical decision has been made to transfuse WB in patients with life-threatening hemorrhagic shock, we recommend the use of group O WB from donors with low anti-A/B titers when logistical constraints preclude the rapid availability of ABO group–specific WB and reliable group matching between donor and recipient is not feasible.

Meta-analysis of plasma to red blood cell ratios and mortality in massive blood transfusions for trauma §,§§

BACKGROUND The current military paradigm for blood transfusion in major trauma favours high plasma:RBC ratios. This study aimed determine whether high plasma:red blood cell (RBC) ratios during massive transfusion for trauma decrease mortality, using meta-analysis of contemporaneous groups matched for injury severity score. METHODS A systemic review of the published literature for massive blood transfusions in trauma was performed. Patients were categorised into groups based on plasma:RBC transfusion ratios. Meta-analysis was only performed when there were no significant differences in Injury Severity Score (ISS) between ratio groups within studies. The main endpoint was 30-day mortality. RESULTS Six observational studies reporting outcomes for 1885 patients were included in this meta-analysis. Five studies were from civilian environments and one from a military setting. Ratio cut-offs at 1:2 were the most commonly reported, demonstrating a survival advantage with higher ratios (OR 0.49, 95% CI 0.31-0.80, p=0.004). Ratios≥1:2 showed a significant reduction in mortality compared to lower ratios (OR 0.56, 95% CI 0.40-0.78, p<0.001). Reducing the cut-off level was still protective (ratios between 1:2.5 and 1:4, OR 0.41), although the confidence interval was wide (0.16-1.00, p=0.05) and data heterogenous (I(2)=78%). Ratios of 1:1 were not proven to confer additional benefit beyond ratios of 1:2 (OR 0.50, 95% CI 0.37-0.68, p<0.001). CONCLUSIONS In groups matched for ISS, there was a survival benefit with high plasma:RBC resuscitation ratios. No additional benefits of 1:1 over 1:2 ratios were identified.

Initial UK experience of prehospital blood transfusion in combat casualties.

T decade of conflict in the Middle East and Central Asia has driven a significant number of improvements in the medical care of military casualties. Exsanguination remains a potentially preventable cause of battlefield mortality and, consequently, the treatment of hemorrhage has been a significant focus trauma care innovation. The last decade has seen the rehabilitation of tourniquets, the development of hemostatic dressings, improvements in paramedical training and the development of deployed trauma systems. Experience derived from the field hospital resuscitation of severely injured patients has led to the development of damage control resuscitation (DCR), which has transformed the treatment of patients with hemorrhagic shock, in both military and civilian practice. DCR combines damage control surgery with hypotensive resuscitation, balanced transfusion therapy, and limited use of crystalloid fluids. DCR has been shown to reverse the triad of coagulopathy, acidosis, and hypothermia, even during the index operation. Commencing this process earlier, by initiating transfusion during the prehospital phase, is conceptually appealing (Fig. 1). The UK Defence Medical Services have, for some time, projected advanced resuscitation capability forward of the hospital, with demonstrable improvements in mortality. The UK Medical Emergency Response Team (Enhanced) (MERT-E) is an advanced medical retrieval platform, as described in detail previously. In addition to standard en route care, the physician-led team can administer resuscitation fluids using the intraosseous and central or peripheral intravenous routes, perform chest decompression (thoracotomy, tube or open or needle decompression), and drug-assisted airway management. The capability was further enhanced by carrying 4 U of packed red blood cells (PRBCs) and thawed fresh frozen plasma (FFP), for prehospital transfusion. This report presents the UK Defence Medical Services’ initial experience of military prehospital transfusion. INDICATIONS AND PRACTICE

Changes in blood transfusion practices in the UK role 3 medical treatment facility in Afghanistan, 2008-2011.

To document blood component usage in the UK medical treatment facility, Afghanistan, over a period of 4 years; and to examine the relationship with transfusion capability, injury pattern and survival.

Prehospital use of plasma: the blood bankers' perspective.

ABSTRACT At the 2013 Traumatic Hemostasis and Oxygenation Research Network’s Remote Damage Control Resuscitation symposium, a panel of senior blood bankers with both civilian and military background was invited to discuss their willingness and ability to supply prehospital plasma for resuscitation of massively bleeding casualties and to comment on the optimal preparations for such situations. Available evidence indicates that prehospital use of plasma may improve remote damage control resuscitation, although level I evidence is lacking. This practice is well established in several military services and is also being introduced in civilian settings. There are few, if any, clinical contraindications to the prehospital use of plasma, except for blood group incompatibility and the danger of transfusion-induced acute lung injury, which can be circumvented in various ways. However, the choice of plasma source, plasma preparation, and logistics including stock management require consideration. Staff training should include hemovigilance and traceability as well as recognition and management of eventual adverse effects. Prehospital use of plasma should occur within the framework of clinical algorithms and prospective clinical studies. Clinicians have an ethical responsibility to both patients and donors; therefore, the introduction of new clinical capabilities of transfusion must be safe, efficacious, and sustainable. The panel agreed that although these problems need further attention and scientific studies, now is the time for both military and civilian transfusion systems to prepare for prehospital use of plasma in massively bleeding casualties.

Taking transfusion forward.

In 2014, the nation commemorated the start of World War I. Conflict has always been a potent stimulus to medical innovation and transfusion medicine is no exception. The Spanish Civil War, both World Wars and more recent conflicts have led to significant advances in the practical application of

Mass casualty events: blood transfusion emergency preparedness across the continuum of care.

Transfusion support is a key enabler to the response to mass casualty events (MCEs). Transfusion demand and capability planning should be an integrated part of the medical planning process for emergency system preparedness. Historical reviews have recently supported demand planning for MCEs and mass gatherings; however, computer modeling offers greater insights for resource management. The challenge remains balancing demand and supply especially the demand for universal components such as group O red blood cells. The current prehospital and hospital capability has benefited from investment in the management of massive hemorrhage. The management of massive hemorrhage should address both hemorrhage control and hemostatic support. Labile blood components cannot be stockpiled and a large surge in demand is a challenge for transfusion providers. The use of blood components may need to be triaged and demand managed. Two contrasting models of transfusion planning for MCEs are described. Both illustrate an integrated approach to preparedness where blood transfusion services work closely with health care providers and the donor community. Preparedness includes appropriate stock management and resupply from other centers. However, the introduction of alternative transfusion products, transfusion triage, and the greater use of an emergency donor panel to provide whole blood may permit greater resilience.