Reducing Blood Transfusions in Critically Ill Patients

Anemia, or low red blood cell count, is a very common condition in critically patients admitted to intensive care units (ICU).  Recombinant human erythropoietin (rHuEPO) is a hormone that is produced by cloning human genes for this protein into bacteria, which then produce the rHuEPO protein in large quantities.  Erythropoietin is a hormone that is naturally produced in the kidneys, and stimulates the bone marrow to produce and release red blood cells into the bloodstream (where they pick-up oxygen from the lungs, and distribute it to all of the body’s cells).  Approved by the FDA in 1989, rHuEPO was initially used to treat the severe anemia present in patients undergoing hemodialysis for kidney failure.  The drug is now commonly used, along with other recombinant drugs that stimulate the bone marrow to produce white blood cells and platelets, to treat the anemia of patients undergoing chemotherapy for cancer, and as an alternative to blood transfusions in chronically or critically ill patients with severe anemia.  However, rHuEPO is not cheap.  A typical dose retails for $500-1,000, and must be given once or twice a week.  It is, therefore, important to determine if the use of rHuEPO in critically ill patients can actually decrease the need for blood transfusions, and whether or not the drug improves patient outcomes overall.  There is certainly some evidence to suggest that patients who receive blood transfusions may be at increased risk of developing infection, and in the case of patients with cancer, an increased risk of cancer recurrence as well.  Of course, blood products may also contain infectious disease-causing organisms such as the viruses that cause hepatitis and AIDS, among other nasty bugs (although modern blood screening in the United States has reduced that risk to about one out of every two million units of transfused blood).  Allergic reactions, occasionally life-threatening in severity, may also occur with transfusions.  So, if a relatively nontoxic drug like rHuEPO can significantly reduce the need for blood transfusions among critically ill patients, then many patients could potentially be spared the risks of transfusion.

In this week’s Journal of the American Medical Association (JAMA) is a study that evaluated the use of rHuEPO in anemic ICU patients as a means of preventing or reducing the need for blood transfusions.  The study looked at more than 1,300 ICU patients in 65 different hospitals between December 1998 and June 2001.  A total of 650 patients were randomized to receive weekly rHuEPO injections, and the remaining 652 received placebo injections of saltwater only.  The study confirmed that the ICU patients who had received rHuEPO required a significantly decreased number of blood transfusions when compared to the placebo group.  Patients receiving rHuEPO were 33% less likely to require a blood transfusion for anemia than their placebo group counterparts.  Among those patients receiving rHuEPO who did require blood transfusions, 19% fewer units of red blood cell transfusions were required when compared to patients who had not received the rHuEPO injections. 

These results confirm my own observations in my practice as a cancer surgeon.  While patients with profound anemia (or patients with moderate anemia and underlying diseases that make them intolerant of a low red blood cell count) still often require blood transfusions, I manage most of my patients with well-compensated moderate anemia using rHuEPO injections.  For patients with more severe anemia, or with signs of significant cardiovascular stress secondary to anemia, a combination of rHuEPO injections and judicious blood transfusions are often sufficient to raise the red blood cell count to an acceptable level.  The JAMA study did not identify any improvements in patient complications or death rates, but this is not surprising in view of the relatively short duration of the study, and the rather small number of patients studied.  The complications associated with transfusion-related infections often take many years to become clinically apparent following blood transfusion.  The study’s conclusions are important in that they confirm that rHuEPO, when used in the proper setting, can significantly reduce the need for blood transfusions in critically ill patients.  At the same time, as pointed out in an accompanying JAMA editorial, you would have to treat approximately 10 patients with rHuEPO to avoid transfusion in one patient.  Also noted is the persistent belief by many physicians that red blood cell levels (referred to as the hematocrit) must be kept at a relatively high concentration for most patients.  Traditionally, physicians have been taught that the hematocrit should not be allowed to fall below 30%.  However, recent research suggests that the hematocrit can be allowed to decline to as low as about 20-25% before most patients will begin to experience serious side effects from their anemia.  Thus, lowering the transfusion threshold for hematocrit values would, in and of itself, spare many anemic patients a transfusion.  Unfortunately, most of the research that has advocated the safety of lower hematocrit values did not study ICU patients who were critically ill.  While the JAMA study has not completely addressed all of the controversies relating to blood transfusion, it nonetheless provides interesting and useful data to physicians and patients alike.

Briefly…

Alcohol Consumption & Risk of Breast Cancer

British Journal of Cancer:  A large European study of over 58,000 women with breast cancer and 95,000 women without breast cancer suggests that heavy alcohol consumption increases the risk of developing breast cancer.  When compared to nondrinkers, women who consumed one glass of wine or beer per day, or one shot of liquor per day, experienced a 7% increase in lifetime risk of developing breast cancer.  Women who consumed six or more glasses of alcoholic beverages experienced a 46% increase in their lifetime risk of developing breast cancer.  Past studies have revealed contradictory conclusions regarding the effects of alcohol consumption on breast cancer risk.  This study strongly suggests that heavy and regular drinking can substantially increase a woman’s lifetime risk of developing breast cancer. 

Calcium Intake & Prostate Cancer Risk

Journal of Urology:   A new study looked at the level of calcium intake in the diet, and analyzed the effects of calcium intake on prostate cancer risk.  A total of 454 male patients, aged 46 to 92 years, were included in the study.  Sixty-nine of these men were diagnosed with prostate cancer during the course of the study.  Following diet surveys and data analysis, the study concluded that high levels of calcium intake did not appear to correlate with either an increase or a decrease in the risk of prostate cancer.  This finding contradicts research published last year that suggested high dietary calcium levels were associated with an increased risk of developing prostate cancer.  Ultimately, it will require a very large international multicenter trial, involving thousands of study volunteers, to definitively determine the role, if any, of calcium intake in the development of prostate cancer.  Still, it is important to note that this study did not identify any increase in the risk of developing prostate cancer among men with high levels of calcium in their diet.