Should Patients in Intensive Care Units Receive Erythropoietin?
Authors: Jeffrey L. Carson
Journal: JAMA (2002)

REDUCING THE FREQUENCY OF RED BLOOD CELL TRANSfusion is a goal of modern blood management. The primary driving force during the past 15 years has been safety. In the mid 1980s the HIV (human immunodeficiency virus) epidemic and frequent transmission of hepatitis C led to careful examination of transfusion practices. A review of the data available then showed no evidence for maintaining hemoglobin concentrations at 10 g/dL or hematocrit at 30%, the so-called 10/30 rule. Subsequent new guidelines urged a lower threshold and consideration of symptoms and other clinical parameters, although clinical judgment was the cornerstone of many of the recommendations. Blood transfusion has many known adverse effects aside from the potential transmission of infectious disease, including allergic reaction; febrile, nonhemolytic transfusion reactions; red blood cell alloimmunization; and leukocyte/platelet alloimmunization. In most patients these events have few clinical consequences. Less common but more serious adverse effects include acute hemolytic reactions, delayed hemolytic reactions, and transfusion-related acute lung injury. Most acute hemolytic reactions from ABO incompatibility are caused by human error, resulting from a patient receiving an incorrect unit of blood. Allogeneic transfusion has been suggested to have an immunomodulating effect that increases the risk of cancer recurrence and bacterial infections, but evidence from a randomized trial comparing autologous with allogeneic transfusions in patients with colon cancer showed no association of allogeneic transfusions with cancer. Trials have yielded inconsistent results regarding the risk of bacterial infections. It is not known whether leukodepletion will reduce the immunomodulating effect of allogeneic transfusion. During the past decade the safety of the blood supply with regard to infectious disease transmission has greatly improved. Very sensitive assays have been developed that detect disease at lower concentrations and shorten the window between the onset of disease and detection by screening tests. More recently, an even more sensitive technique, nucleic acid amplification testing, has been implemented in the United States. A recent study evaluated the rates of viral markers in about half of the US blood supply for a 3-year period and estimated the residual likelihood of a given unit having detectable levels of hepatitis B, hepatitis C, HIV, or human T-lymphotrophic virus. After screening the blood supply with the new nucleic acid amplification tests, the estimates of residual units of infected blood donated by repeat donors were 1 per 1.935 million for hepatitis C and 1 per 2.135 million for HIV. The rates for first-time donors were about twice the rates for repeat donors. This improvement in detection of infected donated blood is a remarkable achievement of investigators, the blood banking community, and regulators. But even these low rates are not good enough. While the goal is achieving a “zero”-risk blood supply, what price is the United States willing to pay to achieve this? For example, one of the latest US policies excludes donors who lived in the United Kingdom and parts of Europe. As a result, about 2% to 5% of the donor pool can no longer donate blood, reducing the donor pool and increasing the likelihood of blood shortages. This is good policy if it results in improved safety. However, while blood transfusion can transmit bovine spongiform encephalopathy, the infectious agent that causes variant Creutzfeldt-Jakob disease, in sheep, the risk in humans is uncertain. Thus, the current policy is designed to reduce the risk of a possible (unknown) dangerous infection at the cost of increasing the possibility of blood shortages. Erythropoietin, which stimulates red blood cell production and thereby reduces the need for transfusion, has been proposed as a possible alternative to blood transfusion for some patients. A previous study found that when 160 critically ill patients were randomized on intensive care unit (ICU) day 3 to erythropoietin, 300 U/kg, or placebo daily for 5 days followed by every-other-day administration, eryth-