“Saving blood, saving money, saving lives”

You’ve heard it before, but it bears repeating: Quality patient care is our first and most essential focus.

Now imagine a procedure performed about 15 million times per year in U.S. hospitals that increases the likelihood of death by 70 percent and the risk of infection by about 80 percent, and is associated with other complications such as acute respiratory distress syndrome.

This procedure, performed at an annual cost of $10 billion to $15 billion, is blood transfusion. It is the single most commonly coded procedure for hospital discharges in the United States, according to the Agency for Healthcare Research and Quality.

Interviews with several of our own faculty suggest that improving the quality of care for our patients by developing literature-based protocols for blood transfusion and reducing adverse events is good medicine. And it also saves money.

So we’ve gathered a team of physicians, nurses and laboratory staff to develop common protocols to ensure an evidence-based approach to blood product transfusion. In Gainesville, this team will be led by Marc Zumberg, M.D., an associate professor of medicine, and Philip Efron, M.D., an assistant professor of surgery and anesthesiology. In Jacksonville, the team leaders will be David Wolfson, M.D., an assistant professor of pathology and laboratory medicine, and Agnes Aysola, M.D., an assistant professor of pathology and laboratory medicine.

Each year, approximately 28,000 units of red blood cells are transfused at Shands at UF, and about 11,000 units at Shands Jacksonville. Although the direct cost of each unit of blood is about $175, the total cost is much greater.

After precisely mapping all diagnostic, therapeutic, technical, laboratory, logistic, administrative and informational activities involved in the transfusion of blood in real-world surgical settings, researchers constructed an activity-based cost model capturing all the actual direct and indirect costs of acquiring, delivering, administering and monitoring red blood cell transfusions from the hospital perspective. (Transfusion 2010; 50:753-65) This yielded an estimate of $520 to $1,180 for the total cost per unit of blood that reflects the complexities of real-world blood utilization, depending on the circumstances surrounding the transfusion.

Even if the average were at the low end (e.g., $600 per unit), a reduction of only 10 percent across Shands at UF and Shands Jacksonville (i.e., about 4,000 units) would save $2.4 million per year.

Achieving such a reduction is a realistic goal. According to data from the University Health System Consortium, which consists of 93 peer institutions, use of red blood cell units by Shands at UF per annual inpatient discharges is 0.87. When UHC hospitals are sorted by numbers of inpatient discharges, all hospitals of our size or larger have lower rates of red blood cell use. For example, the rates for Barnes-Jewish (Washington University), Vanderbilt University and University of Arizona are 0.68, 0.64 and 0.56, respectively.

In addition, data reported to UHC indicate an annual use of 13,500 units of plasma by Shands at UF and 8,200 units by Shands Jacksonville. Plasma is the liquid part of the blood in which the blood cells are suspended. Plasma for transfusion is usually termed fresh-frozen plasma, or FFP. FFP is commonly used for a wide variety of indications, but review of the literature would suggest that the evidence favors plasma transfusion in only a very limited number of clinical situations.

Specifically, a recent report from a blue-ribbon multidisciplinary guidelines panel (Transfusion 2010;50:1227-1239), which conducted a systematic review and meta-analysis of randomized and observational studies, concluded that FFP was indicated in patients with blood loss requiring massive transfusion and in patients with warfarin therapy in association with intracranial hemorrhage. The panel did not favor plasma transfusion for other selected groups of patients.

Other opportunities become apparent after reviewing the contemporary medical literature and listening to our hematology faculty’s expert judgments. For example, it is still common practice to attempt to correct “abnormal” laboratory values of hemostasis prophylactically in patients with liver disease by administering blood products. But a recent review of the literature suggests that such a practice is not supported by the evidence. Thanks to tremendous progress in the understanding of hemostatic function in patients with liver disease, the long-standing dogma that patients with liver disease have a bleeding tendency that can be corrected by transfusion no longer appears to be supported by data from both clinical and laboratory studies (Blood 2010;116:878-885). Rather, it appears that attempts at preoperative transfusion in patients with liver disease does not reduce, and may in fact promote, bleeding.

A recent review in Critical Care Medicine classified 45 studies including 272,596 patients as 1) risks outweigh benefits, 2) neutral risk and 3) benefits outweigh risks. In 42 of 45 studies, the risks of red blood cell transfusion outweighed the benefits, the risk was neutral in two studies, and the benefits outweighed the risks in a single subgroup of a single study (elderly patients with an acute heart attack and a hematocrit less than 30 percent).

Still, blood transfusion can be a life-saving procedure for many patients in specific situations involving hemorrhage from trauma or surgery, or in many cases of severe anemia in patients who are critically ill. The data are quite sobering, however. As suggested in an editorial by Drs. Howard Corwin and Jeffrey Carson (NEJM 2007;356:1667-8): "Red-cell transfusion should no longer be regarded as 'may help, will not hurt' but, rather, should be approached as 'first, do no harm.’”

Yet over the past several decades, with the exception of concern about transfusion-related infection that has been largely eliminated thanks to effective testing for hepatitis and HIV, the practice of transfusion has grown dramatically under the "may help, can't hurt" mindset.

In 1999, the results of an important clinical trial, Transfusion Requirements in Critical Care, were reported (NEJM 1999;340:409-17). In this randomized, controlled study involving critically ill adults, a liberal strategy (transfuse if the hemoglobin level drops below 10.0 g/dL) was compared with a restrictive strategy (transfuse if hemoglobin drops below 7.0 g/dL). Patients randomly assigned to restrictive management received 54 percent fewer red-cell units than did the liberal management group, and the restrictive strategy was found to be at least as effective as the liberal strategy with respect to mortality. In patients who were less acutely ill or under 55 years of age, the restrictive strategy was actually superior, in that compared with the liberal strategy it was associated with lower mortality.

A study of children in a Pediatric Intensive Care Unit (NEJM 2007;365:1609-19) reached similar conclusions. Using multiple organ dysfunction as an endpoint, a restrictive transfusion strategy was at least equivalent to the liberal strategy in this outcome, and was associated with a 44 percent reduction in the number of red-cell transfusions.

These findings come at a time when a quarter of a century of research demonstrates that transfused patients, in general, have much poorer outcomes than similar untransfused patients, and that patients who receive more transfusions do progressively worse in a dose-dependent fashion (Transfusion 2005 45[Supplement]: 33S-40S).

More recent studies reveal that among patients who are treated for trauma, blood transfusion increases pneumonia, acute respiratory distress syndrome and mortality (J. Trauma 2005, 59:19-23). Among burn patients, blood transfusions increase mortality and infection, controlling for indices of burn severity (Crit Care Med 2006, 34:1602-9).

The history of blood transfusion is intertwined with the history of medicine generally, and is one of the great examples of true translational science. The first successful transfusion of human blood was performed by Dr. James Blundell, a British obstetrician, who treated a woman who developed postpartum hemorrhage using her husband's blood. Through the 1800s, transfusions were only infrequently performed (e.g., to treat conditions such as hemophilia), as many recipients died due to what we now know were hemolytic reactions from blood group incompatibility.

The ABO blood group system was discovered by the Austrian Karl Landsteiner, M.D., in 1901 (for which he won the Nobel Prize in Medicine or Physiology in 1930), providing the scientific basis for improving the safety of blood transfusion. In 1939, Drs. Landsteiner, Levine and Weiner discovered the Rh blood group system. In 1961, Rh immune globulin was commercially introduced to prevent Rh disease in newborns of Rh-negative women.

Since then, advances have occurred in the systems of infection screening, storage, distribution and processing of blood products. Currently accepted blood transfusion practices evolved prior to the concepts of randomized trials and clinical outcomes studies, however, and developed all the sanctity expected of time-honored therapies.

In summary, interviews with faculty involved in blood transfusion suggest a consensus: As is often the case in quality improvement initiatives, improving the quality of care for our patients by developing literature-based protocols for blood transfusion and reducing adverse events will also result in cost savings. I would add, in the spirit of the goals of our Clinical and Translational Science Award, that research on blood transfusion has progressed through the first two translational stages: from "T1" (discovery of blood groups, fractionation and storage methods, etc., translated to individual patient treatment), to "T2" (defining risk groups and hemoglobin targets for translation to optimal clinical practice).

It is now time to progress to the "T3" phase, in which accumulated knowledge on best practices can be disseminated to our physicians, nurses and students, so that known best practices can be achieved across our health-care system in a manner that saves blood, saves money and saves lives.

Forward Together,

David S. Guzick, M.D., Ph.D. Senior Vice President, Health Affairs President, UF&Shands Health System