Advancements in transfusion medicine over the

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1 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page 46 Deborah J. Tolich, RN, BSN Alternatives to Blood Transfusion Abstract Blood transfusion therapy in the 21st century continues to present limitations regarding efficacy and risks. Blood management partners optimal blood transfusion therapy with anemia management that incorporates nonblood strategies and techniques. A planned approach to anemia prevention, identification, and treatment can reduce the need for blood transfusion and improve patient outcomes. The use of pharmaceutical agents and tools to minimize blood loss also leads to blood transfusion reduction. Nurses play an integral role in affecting the use of alternatives to blood transfusion. Through assessment, communication, and an understanding of blood management strategies, nurses are patients frontline innovators in promoting best practices. Advancements in transfusion medicine over the past 20 years include evidence that blood transfusion doesn t necessarily contribute to better outcomes. 1,2 In 1999, Hebert et al explored blood transfusion in critical care and found that a restrictive transfusion approach (hemoglobin 7-9 g/dl) leads to equivalent and in some cases better outcomes than a liberal transfusion practice (hemoglobin >9 g/dl). 3 This study put into question the efficacy of transfusion in regard to patient outcomes. Transfusion is common in the intensive care unit, with 40% to 50% of patients receiving 1 to 5 units of packed red blood cells. Blood product ordering practice is inconsistent from physician to physician, which creates disparities when and for what reason patients are transfused. A minimum transfusion trigger has not been well established because of the variability of patient comorbidities and anemia tolerance. Evidence suggests that most patients can safely tolerate anemia of 7 g/dl of hemoglobin in the absence of active bleeding. The decision to transfuse should be based on physiologic benefit rather than adherence to an arbitrary numeric transfusion trigger. 4(p. S33) Shortages are of concern because on any given day in the United States, only a 2-day supply of blood is available. At times, elective procedures are canceled because of the unavailability of blood products. Blood shortages are expected to continue and worsen. Although donations have increased, demand has continued at a much faster rate. In the future, demand may far exceed supply, and resource allocation will become a reality. Screening and testing of donor blood continue to improve; however, Author Affiliation: Director of Blood Management, Cleveland Clinic Health System West Market, Cleveland, Ohio. Corresponding Author: Deborah J. Tolich, RN, BSN, Cleveland Clinic Health System West Market, Lorain Avenue, Cleveland, OH Journal of Infusion Nursing

2 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page 47 blood transfusions do not and will not remain risk free. Regardless of the amount of testing, the largest risk is that of the unknown. 5 Blood management is the safe, effective use of blood products combined with anemia prevention, detection, and treatment. The use of a comprehensive approach to blood transfusion can be a difficult concept for many healthcare professionals. The perception in healthcare has been that blood saves lives. This is antiquated thinking that has not been based on scientific evidence. The combination of an inadequate blood supply and a lack of evidence in efficacy has led to the growing interest in alternatives and adjuncts to transfusion therapy. 6 THE PHILOSOPHY OF BLOOD MANAGEMENT Blood management, which draws from various disciplines, incorporates scientific medical evidence, ethics, economics, religion, and law. Formalized blood management programs have been established in approximately 120 sites across the United States. 7 These programs are managed by registered nurses or highly trained individuals with a background in healthcare or business administration. The benefit of having a dedicated blood management service is the continuous gate-keeping of opportunities for improvement and emerging technology. A newer concept in blood management is that consulting firms conduct a current-practice assessment in order to identify areas for improvement. These consultants offer various services to improve blood safety, administration, and use of blood management strategies and technology. 8 For nurses, knowledge and implementation of alternatives not only affect patient outcomes but also improve blood use. Table 1 describes general principles used in blood management ANEMIA: THE HEART OF BLOOD MANAGEMENT TABLE 1 General Principles of Blood Management Develop a comprehensive plan of care regarding anemia prevention, early identification, and treatment. Consider elective or potential procedures in addition to medical history. Incorporate multidisciplinary interventions. Prepare and anticipate for potential complications. Screen for preoperative or preprocedure anemia and treat as appropriate. Perform decisive interventions for actively bleeding patients. Be flexible in modifying routine practices. Engage healthcare professionals experienced in blood management. Reduce iatrogenic blood loss through limiting laboratory draws and wastage through catheter draws. Restrict use of preoperative antiplatelet and anticoagulants. Use algorithms, guidelines, and protocols for incorporating blood management. mia resulting from disease hemolysis. Anemia occurs among economically deprived populations who suffer from nutritional deficiencies and other disease states. Another population of individuals affected by anemia is persons with AIDS. Anemia places individuals at risk for blood transfusion therapy, which in turn creates further risk of immune suppression and potentially an increase in mortality It is important for nurses to identify the signs and symptoms of anemia during their assessment, including fatigue, headaches, tachycardia, pallor, sensitivity to cold, restless legs, and an inability to concentrate. Laboratory values that help discover the contributing cause and aid in a differential diagnosis include complete blood count, reticulocyte count, peripheral smear hemoccult, and iron studies. Nurses should be able to recognize iron deficiency through lab values because it can be easily treated with iron supplementation (Table 3). Anemia is not a disease but a symptom; identifying its cause is imperative for proper blood management. There are several major contributing factors for anemia: nutritional deficiencies, blood loss, kidney disease, medications, and chronic diseases. Anemia can impinge on health throughout the life span. This is especially true for elderly persons, whose quality of life can be greatly affected by the symptoms of anemia. Prevalence of anemia is shocking not only from a worldwide perspective but also when broken down into subcategories (Table 2). Malaria-endemic areas of the world are plagued with ane- TABLE 2 Anemia Prevalence One third of patients undergoing elective orthopedic procedure are anemic going into surgery Gynecologic conditions Iron deficiency in children and adolescents Greater than 50% of oncology patients Elderly men: 3%-61% Elderly women: 3.4%-41% Vol. 31, No. 1, January/February

3 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page 48 TABLE 3 Identification of Iron-Deficiency Anemia TABLE 4 Patient Education for Oral Iron Laboratory Values Hemoglobin MCV MCH MCHC Reticulocyte Serum iron TIBC Bilirubin Platelets Iron Deficiency Normal or decreased Increased Normal or decreased Normal or Increased Do not take with coffee, tea, eggs, or milk. Take with citrus fruits or supplement of vitamin C to increase absorption. Do not take with calcium products. Stop taking multivitamins with vitamin E when taking iron. Keep out of reach of children; overdoses can be fatal. Can cause constipation, stomach irritation, or abdominal cramping. To reduce symptoms, increase fluids, fiber, and/or take a mild stool softener. Causes stool to turn dark green or black. Abbreviations: MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean cell hemoglobin concentration; TIBC, total iron-binding capacity. MEDICATIONS, VITAMINS, AND SUPPLEMENTATION A class of medication available for the treatment of anemia is erythropoietic stimulating agents (ESAs). Although the Food and Drug Administration has issued a black-box warning regarding these products, it should be stressed that ESAs have been found to be safe and effective for approved indications. An important consideration, however, for the use of ESAs in blood management is the hyperproliferation of red cells in individuals with certain comorbidities, which may increase their risk of thrombosis, myocardial infarction, and stroke. Patients who are receiving ESAs require monitoring of hypertension and response to treatment. Uncontrolled hypertension is a contraindication for drug administration. This class of medications plays an important role in blood management. By increasing red cell production, patients with preoperative anemia can be optimized before elective surgery, thereby preventing or minimizing postoperative anemia requiring blood transfusion. Stable patients with chronic blood loss can also benefit from treatment through anemia correction. ESAs can be used for moderate acute blood loss in stable patients. It is important to check iron levels because ESAs require adequate iron stores to work effectively. Iron supplementation should be considered concurrently because these products may cause a functional iron deficiency. White cell growth factors are another class of blood cell growth factors and are used mainly in the oncology setting Iron preparations are useful in replacing iron lost through bleeding or nutritional deficiency. Oral iron has been modernized with newer and improved products that have fewer side effects and better absorption mechanisms. Patient education is key for oral iron adherence, and sev- eral points should be covered (Table 4). Many nurses consider intravenous (IV) iron as having the potential for serious and even fatal reactions. This was true with iron dextran; however, more recent IV iron preparations conform to a very high safety standard. Iron sucrose and ferric gluconate do not require a test dose and can be given either by infusion or IV push. Side effects such as hypotension are often mild and can be due to the rate of infusion. Elderly patients who weigh less than 70 kg may be at risk for a labile reaction that occurs when the iron is not readily absorbed and becomes free-floating in the blood stream. Symptoms usually begin several hours after administration and include muscle/joint pain and general malaise. To minimize these side effects, the dose and infusion rate should be decreased and patients can be premedicated with acetaminophen, which may be continued for 24 hours. Nurses can administer IV iron safely and confidently when they have knowledge of these products Vitamins essential for red cell production include B 12, folic acid, and vitamin C. Elderly persons are most at risk for B 12 nutritional deficiency. This vitamin combines with intrinsic factor for absorption, and because some individuals do not produce intrinsic factor, it results in pernicious anemia. Folic acid is important during infancy and pregnancy and helps to maintain new cells. Several conditions increase its need, such as alcohol abuse, malabsorption, and kidney and liver disease. Vitamin C, a water-soluble vitamin, is not stored in the body. It is essential for tissue repair and collagen formation and is needed for wound healing. These 3 vitamins aid in the production of red cells and are important when considering anemia treatment BLOOD LOSS PREVENTION The strategy of minimizing blood loss during invasive procedures and surgeries has an impact on blood compo- 48 Journal of Infusion Nursing

4 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page 49 nent use. Existing and emerging technologies achieve that goal. Diathermy and laser technology are examples of technology that seals blood vessels to decrease bleeding. Drugs can affect coagulation and decrease blood loss. Antifibrinolytic drugs and clotting factors, such as factor VIIa, are being effectively used, as are fibrin glues, sealants, and platelet-rich plasma. Minimally invasive and robotic surgeries also aid in the reduction of blood loss. 30 Predonation of autologous blood (PAD) has been used for more than 2 decades. In theory, it seems to be a good alternative for avoiding allogeneic transfusions; however, there are significant factors to be considered. First, patients who predonate are more likely to enter the operating room anemic, which increases their likelihood of requiring a transfusion. Second, in most cases, if autologous blood is not transfused, it is discarded. Studies in orthopedic surgery in which PAD is a common practice have shown that upwards of 60% of PAD blood is wasted. 32 Finally, although rare, risks associated with PAD include clerical errors and bacterial contamination. 31 Before using PAD, the patient s age, comorbidities, baseline hemoglobin and hematocrit, and appropriateness of procedure should be considered. For example, during total joint replacement or revision and bilateral procedures in which blood loss is greater than primary procedures, PAD may be the better choice. Using autologous blood through acute normovolemic hemodilution (ANH) and cell salvage is an option in the operating room. ANH removes approximately 1 to 2 units of blood from a patient either in the holding area or in the operating room. The volume removed is replaced with a crystalloid solution. The process of removing blood and replacing it with an IV solution dilutes the patient s blood; therefore, when blood is lost during surgery, fewer red cells are lost. The collected blood is returned either near the end of the surgery or in the recovery area. A benefit of ANH over PAD is that the blood is fresh and can immediately support oxygen delivery. Stored PAD blood develops storage lesions and lacks 2-3 diphosphoglycerate, an enzyme that augments oxygen delivery, which limits oxygen delivery once transfused. 33 Cell salvage collects blood normally lost during a surgical procedure, removes debris, and returns it to the patient. The blood is collected from the surgical field and anticoagulated. Once a sufficient quantity has been collected, it is spun down to separate and wash the red cells before reinfusion. The process rinses out clotting factors, imposing limitations in its use. Cell salvage may be safely used in cancer procedures with leukocyte filters to prevent reinfusion of tumor cells. 34 Postoperative blood salvage is another way of returning autologous blood to a patient. A drain or chest tube is connected to a collection device that allows the drainage to be returned to the patient. Generally, blood can be collected for a maximum of 6 hours until it must be returned. Some postoperative systems can wash out debris before the blood is reinfused. Surgical technology continues to expand and with it, tools that minimize blood loss and decrease the trauma of surgery. Not only do these methods decrease blood use but they also accelerate recovery while minimizing complications. Iatrogenic blood loss is an area that is often overlooked in the hospital setting. The primary cause is frequent blood draws. Phlebotomy of as little as 20 ml/day can place patients at risk within a few days. Studies in intensive care units have acknowledged alarming amounts of blood lost through phlebotomy. It is common practice to obtain blood samples from invasive catheters, which requires 5 to 10 ml of blood to be discarded to clear it before drawing the sample. This practice significantly increases the amount of blood lost for laboratory testing. It has been established that patients can lose 240 ml to more than 750 ml of blood in a hospital stay. Measures that can be taken to reduce this from happening are the elimination of unnecessary lab tests, batching lab tests, using previously drawn blood for additional testing when available, and incorporating low- or reduced-volume laboratory tubes. Intensive care units should consider using reservoir systems that allow for the return of discarded blood to the patient. Standing orders should be reviewed and revised to remove and/or limit serial lab testing. 35,36 FUTURE TECHNOLOGY Technology is exploring different mechanisms of action in order to grow blood cells. Newer medications to stimulate blood cell growth are in developmental stages, including an oral agent that would simplify administration of red cell growth factors. One such product is hypoxiainducible factor, currently in phase 2 clinical trials. Erythropoietin is activated during hypoxia, and this particular product simultaneously increases iron absorption necessary for red cell production. 37 Phase 3 clinical trials have been completed on a product that activates erythropoietin receptor sites for an extended period of time. Continuous erythropoiesis receptor activator has yielded positive results in studies with chronic kidney disease. Solutions with oxygen-carrying capacity have been in development for more than 2 decades. There are 2 classes of products: one is chemically derived and the other is hemoglobin extracted from red blood cells. To date, these products remain in clinical trials and have raised many questions regarding safety. Oxygen-carrying solutions have been found to be short-acting and require adequate kidney and liver function for excretion. If approved, they will provide a bridge in combination with growth factors and other alternatives to reduce the use of blood products. Vol. 31, No. 1, January/February

5 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page 50 WHAT CAN NURSES DO? Nurses can commit to life-long learning and keep abreast of transfusion practice and anemia management. Strong assessment skills lead to recognition of anemia. A proactive approach is needed to identify individuals at risk for anemia and blood transfusion, however. A partnership between physicians and nurses is necessary to develop a comprehensive approach for anemia and transfusion practice. In addition, patients are often unaware of options beyond blood transfusion. Nurses can bridge this knowledge gap and should include patient education regarding available alternatives in their practice. Another important role for nurses is safe transfusion practice. All blood banks function according to set transfusion criteria. Blood transfusion in any setting should be clearly indicated and meet established criteria. It is not uncommon for patients to present for outpatient blood transfusion with a prescription and no further medical information. An example of where this can lead to potential unsafe transfusion practice is when there is a history of organ transplantation, and irradiated blood products are indicated. To improve safety, outpatient centers may consider requiring additional medical information in addition to a written indication for the transfusion. Preprinted blood-component order forms are another mechanism to promote appropriate use of blood products and help physicians stay within established criteria. Nurses should be prepared to educate patients regarding transfusion therapy and possible alternatives. CONCLUSION Today s healthcare environment encourages the use of a comprehensive approach to blood management. Regulatory agencies are exploring minimum requirements for blood safety, administration, and appropriate use of blood products. The low blood supply and risk of disease transmission are ongoing threats. Medical evidence suggests that transfusion can lead to poor outcomes and should be used carefully. By applying principles of anemia prevention, detection, and combined modality treatment, we can not only affect patient outcomes but also preserve the blood supply for those who will benefit the most. R E F E R E N C E S 1. Thomas D, Thompson J, Ridler B. Who Needs Transfusion? A Manual for Blood Conservation. Shrewsbury, Shropshire, UK: TFM Publishing; 2005: Spiess BD, Spence RK, Shander A. Medical ethics, transfusion, and the standard of practice. In: Perioperative Transfusion Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006: Hebert PC, Wells G, Blajchman M, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340(6): Marshall JC. Transfusion trigger: when to transfuse? 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6 _JIN3101-Tolich.qxd 1/4/08 3:02 PM Page Ferrlecit. Watson Pharmaceuticals. Accessed March 5, For information pertaining to vitamin B 12 : MayoClinic online, B12/NS_patient-vitaminb12. Accessed March 5, National Institutes of Health. asp. Accessed March 5, Medline. plus/ency/article/ htm. Accessed March 5, Holcomb JB. Methods for improved hemorrhage control. Crit Care. 2004;8(Suppl 2):S57-S Billote DB, Glisson SN, Green D, Wixson RL. A prospective, randomized study of preoperative autologous donation for hip replacement surgery. J Bone Joint Surg Am. 2002;84A(8); Kirschman RA. Finding alternatives to blood transfusion. Nursing. 2004;34(6): Hansen E, Bechmann V, Altmeppen J. Intraoperative blood salvage in cancer surgery: safe and effective? Transfusion Apheresis Sci. 2002;27(2): Segal JB, Blasco-Colmenares E, Norris EJ, Guallar E. Preoperative acute normovolemic hemodilution: a meta-analysis. Transfusion. 2004;44: Woodhouse S. Complications of critical care: lab testing and iatrogenic anemia. MLO Med Lab Obs. 2001; Barie PS. Phlebotomy in the intensive care unit: strategies for blood conservation. Crit Care. 2004;8(Suppl 2):S34-S Adamson JW. A novel approach to treating anemia: stabilization of hypoxia-inducible factor (HIF). An expert interview. Nephrology. 2006;3(2). Accessed December 16, Fishbane S. Continuous erythropoietin receptor activator (CERA): an innovative agent for correction of anemia. An expert interview. Nephrology. 2006;3(2) Accessed December 16, Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care. 2004;8(Suppl 2):S61-S64. Vol. 31, No. 1, January/February