In this special report, we review the recent evidence on transfusion protocols and other strategies for improving mortality in patients who have coagulopathy and/or significant hemorrhage following trauma or major surgical procedures.
Read on to find out more.
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Challenge of hemostasis
A hemostasis advisory panel was convened in 2008 to discuss optimal methods for using both new and conventional blood products and therapeutics. The panel said that, in order to help prevent hemorrhage, physicians should use all available laboratory assessment tools to provide bleeding status in a timely manner. They should also weigh the benefits against the risks of transfusion to ensure that patients are not being under- or over-treated.
In their review of the panel’s findings, Jerrold Levy (Emory University School of Medicine, Atlanta, Georgia, USA) et al acknowledge that there is limited clinical evidence that can help physicians to effectively maintain patients’ hemostatic balance; therefore, “ongoing communication among advocates for hemostasis research from all disciplines is critical to improving treatment and patient outcomes.”
The effect of blood storage
An editorial by Philip Spinella (St. Louis Children’s Hospital, Missouri, USA) and colleagues addressed the issue of whether blood-product storage duration has an effect on survival in critically ill patients (such as those with coagulopathy or organ failure).
Historically, whole blood was usually transfused, and component transfusion did not take over until the 1980s. Component transfusion encouraged stability, but the small number of patients who become critically ill post-transfusion may have worsened as a result of receiving “older” components.
Spinella and colleagues highlight recommendations on how to conduct good retrospective reviews on the effect of red blood cell (RBC) storage duration on outcomes. Studies that adhere to this model have found that greater storage duration is associated with higher rates of morbidity and mortality. However, as noted below, there are also risks associated with fresh whole blood (FWB) use, especially in critically ill patients.
The authors find it “encouraging that there is significant research aimed at determining the efficacy and safety of blood products transfused to critically ill patients,” and are looking forward to the results of current prospective randomized clinical trials.
Use of predictive models to determine benefit of treatment with a high FFP:RBC ratio
Nearly one-quarter of people with traumatic injury present with coagulopathy, but it is not easy to determine at first whether their trauma is severe enough to require massive transfusion (MT). A predictive model could help determine which patients have a better chance of survival with the use of a high fresh frozen plasma:red blood cell (FFP:RBC) resuscitation approach, according to a recent study by Matthew Borgman (Brooke Army Medical Center, San Antonio, Texas, USA) and colleagues.
Borgman et al found that patients with more severe trauma who received transfusions with a high FFP:RBC ratio had nearly 40% improved survival rates. However, as they noted, “a high FFP:RBC ratio does not improve mortality and may cause harm for those at lower risk for a massive transfusion.”
The authors added a caveat that these results will need to be validated in a prospective, interventional trial.
Plasma transfusion
The current model for MT in patients with severe blood loss following trauma is aggressive blood-component therapy, particularly plasma and packed red blood cells (PRBCs). However, the utility of plasma transfusion in people who do not need an MT is unclear, as overaggressive plasma transfusion may lead to a higher rate of complications.
Kenji Inaba (Los Angeles County and University of Southern California Medical Center, Los Angeles, USA) and colleagues recently published a retrospective analysis of their institution’s Institutional Trauma Registry and Blood Bank Database. Plasma transfusion in non-MT patients did not have an effect on survival, but it did lead to more complications, including adult respiratory distress syndrome, sepsis, and pneumonia.
The authors conclude that, “for patients who received blood but not in massive amounts, plasma does not improve mortality and increases complications. Results of this study support the need for evaluation of the optimal point at which aggressive plasma transfusion should be initiated.”
Platelet transfusion
Studies have now begun to look at the role of platelets and whether aggressive platelet transfusion is also warranted. Inaba et al published a retrospective analysis regarding the impact of an increasing apheresis platelet (aPLT):PRBC ratio on trauma patients who required an MT.
A higher aPLT:PRBC ratio (≥1:6) was associated with increased survival rates at both the 12- and 24-hour timepoints, as well as overall survival to discharge. This led Inaba and his team to note that “further prospective evaluation of the optimal platelet ratio and trigger for transfusion in patients undergoing a massive transfusion is warranted”.
What about combat trauma?
In combat, hemorrhage following trauma causes the most potentially preventable deaths. Doctors treating combat injuries need to quickly assess whether an injury is severe enough to warrant an MT.
Claire Larson (United States Army Institute of Surgical Research, Fort Sam Houston, Texas, USA) and her team conducted a retrospective review of 1124 wounded soldiers listed in the Joint Theater Trauma Registry transfusion database. Disconnects between prediction to receive an MT (either yes or no) and actual observed MT led to increased injuries and earlier time of death.
The investigators found that “the decision to implement an MT is based mainly on injury severity (anatomic abnormalities) and is quite subjective, relying heavily on surgeon experience,” and recommend using a predictive model that measures blood pressure, heart rate, base deficit, and hemoglobin.
Separate plasma or platelet components are often unavailable in combat situations. FWB is often used in transfusions in the field, and its associated survival rate is such that the military is considering using it routinely in combat hospitals.
Jeremy Perkins (Walter Reed Army Medical Center, Washington, DC, USA) and colleagues compared FWB versus aPLT in a retrospective review of patients with combat trauma who had received MTs with platelet-containing components. Survival rates were similar between the two groups, with higher respiratory distress rates also noted in patients given FWB. However, transfusion with FWB is not often used in the civilian population because of its short shelf-life and the difficulty in recruiting donors in immediate trauma situations.
Using the military protocol in a civilian setting
Christopher Dente (Emory University School of Medicine, Atlanta, Georgia, USA) and his group devised an MT protocol at their institution that featured a targeted 1:1:1 PRBC:FFP:platelet ratio. They then conducted a prospective study that compared trauma patients given this protocol with an earlier group of patients (age-, gender-, and injury-matched) who received pre-protocol transfusions of ≥10 RBC units.
This protocol dramatically increased the amount of FFP and platelets previously given and led to improved overall patient mortality at 24 hours and reduced early coagulopathy although, in most cases, the 1:1:1 ratio was not fully achieved. There was also greater improvement in 30-day survival in patients with blunt trauma.
Dente and colleagues recommend that “individualized MTPs should be adopted by centers routinely taking care of patients with trauma in an effort to improve the early resuscitations of these critically injured patients.”
Hypotensive resuscitation
Hypotensive resuscitation has been discussed as a potential alternative method of treating trauma patients, as it uses less fluids and blood products. The first randomized trial of intraoperative hypotensive resuscitation (target mean arterial pressure [MAP], 50 mmHg) versus standard resuscitation (target MAP, 65 mmHg) in humans was conducted by C. Anne Morrison (Baylor College of Medicine, Houston, Texas, USA) and colleagues.
Trauma patients with hemorrhagic shock who were given hypotensive resuscitation were less likely to develop coagulopathy or to die from coagulopathy resulting from postoperative bleeding, and had lower immediate postoperative mortality, than those given standard resuscitation. Further investigation is needed to determine whether this technique should be used in this patient population.
Significance of evidence from clinical trials
Nicola Curry (Oxford Radcliffe Hospitals NHS Trust, UK) et al conducted an assessment of 37 systematic reviews of the current evidence regarding diagnosis and management of trauma coagulopathy and transfusion. They found that no review gave useful information on how best to predict coagulopathy, an answer as to whether correcting coagulation parameters will help to improve patient survival, or data correlating blood loss and mortality. There are also major gaps in the evidence regarding the benefits of transfusion for trauma patients.
