Patient Management: Use of Topical Hemostatic and Sealant Agents SHERRI OZAWA, RN

ABSTRACT

Patient blood management is the scientific use of safe, effective medical and surgical techniques designed to conserve blood, prevent anemia, decrease , and optimize in an effort to improve patient outcomes. Perioperative and primary care nurses play a vital role in promoting and making the best use of patient blood management and can play a key role in implementing effective strategies that decrease or eliminate patient exposure to allogeneic blood. The fast and effective minimization of intraoperative bleeding is integral in an effective blood manage- ment program. Topical hemostatic and sealant agents can be used to improve blood conservation, reduce overall procedure time, and contribute to faster patient recovery based on specific clinical situations. The proper selection of hemostatic agents can greatly influence the patient’s clinical outcomes. AORN J 98 (November 2013) 461-478. Ó AORN, Inc, 2013. http://dx.doi.org/10.1016/j.aorn.2013.08.014

Key words: blood, blood transfusion, blood loss, , topical hemostatic agents, sealants.

or many decades, the transfusion of donor on almost any other medical or surgical modality blood has been viewed as a universally and evidence-based practice is often eclipsed by F beneficial and life-saving treatment.1 Blood entrenched beliefs and traditions.1 According to donation has been viewed as the ultimate expres- The Institute of Medicine Survey of Health Care sion of community support to blood recipients, in the United States, there is a large amount of who are often perceived as being in life or death variability in transfusion practices.2 This disparity crises. Blood transfusion also carries deep cultural suggests that the transfusion practices currently meaning, from the magical to the religious.1 For used in many institutions may be inappropriate. To example, Roman gladiators drank the blood of help address this issue, The Society for the Ad- opponents to gain their strength, and the Bible vancement of Blood Management has developed describes blood as “life.”1 The unique place that the Administrative and Clinical Standards for Patient transfusion of blood holds in our culture frequently Blood Management Programs.2 These standards allows the practice to escape the scrutiny levied attempt to bring the aforementioned concepts of

http://dx.doi.org/10.1016/j.aorn.2013.08.014 Ó AORN, Inc, 2013 November 2013 Vol 98 No 5 AORN Journal j 461 November 2013 Vol 98 No 5 OZAWA blood management into everyday clinical practice products, particularly platelets, is one of the most and to act as an aid in the development of patient common causes of morbidity and mortality associ- blood management programs.2 ated with blood transfusions, occurring approxi- Although there are many situations in which blood mately once for every 2,000 to 3,000 transfusions.11 transfusions are medically indicated or even life The transfusion of blood to the wrong patient is saving, numerous studies of clinician practice show also a leading transfusion-associated risk and is that, in some cases, perhaps even as much as half the reported to occur once for every 12,000 to 19,000 time, clinicians transfuse blood without evidence of units transfused.11 clear medical benefit.3,4 Results of recent research Transfusion-related acute lung injury is an im- has shown that allogeneic blood transfusions are portant, life-threatening complication of blood associated with a wide variety of negative clinical transfusion.7 Transfusion-related acute lung injury outcomes.5 In the face of no clear evidence of benefit, is antibody mediated and is caused by the infusion patients often are exposed to potential harm from of donor antibodies.12 This syndrome occurs after transfusions.5 Nurses have a unique role in the pro- transfusion and presents as hypotension, pulmonary cess of blood transfusion and a responsibility to edema, and acute respiratory distress, often ac- understand the implications that blood transfusion companied by fever.12 Reported to occur once has for patients. In the OR, evidence-based blood every 1,000 to 5,000 transfusions, transfusion- management practices are vital in providing com- related acute lung injury is a leading cause of prehensive patient care. The fast and effective mini- transfusion-related morbidity and mortality.7 mization of intraoperative bleeding plays an integral Transfusion-associated circulatory overload is role in an effective blood management program be- another life-threatening transfusion complication cause effective hemostasis has the potential to re- and can occur when large volumes of blood are duce the incidence of surgery-related morbidity and rapidly transfused.13 Symptoms of this syndrome mortality.6 include a rapid increase in blood pressure, periph- eral edema, dyspnea, and orthopnea.13 The inci- TRANSFUSION RISKS dence of transfusion-associated circulatory overload The transfusion of blood products is considered to is difficult to quantify but has been estimated to be a “high-risk” procedure, which has the potential be approximately once for every 100 to 10,000 to expose patients to serious morbidity.7 Studies of transfusions. Patients older than 60 years of age cardiac surgery patients have shown that morbidity and patients with anemia or cardiac or pulmonary and mortality increase with each additional unit of comorbidities are at an increased risk of developing blood transfused.8,9 For example, a study of trauma transfusion-associated circulatory overload.13 patients showed an increase in infections in those patients receiving a single transfusion of packed red PATIENT BLOOD MANAGEMENT blood cells (RBCs).10 This effect was found to be Cost and supply issues are among the factors that dose dependent and increased with each unit of have driven the shift away from traditional trans- blood transfused.10 fusion practices. Although blood product acquisition Contrary to popular belief, the most significant costs are high and continue to rise, the true cost of risks associated with transfusions are not the trans- transfusion is much higher, with calculated costs mission of viruses such as HIV and hepatitis C.11 approaching $1,200 to transfuse a single unit of Since the advent of donor blood testing for HIV RBCs.14 With 15 million units transfused in the and other transmissible infections, the risk of in- United States every year, and many of those for no fectious transmission has dropped dramatically.11 clear clinical reason, there is a significant amount of However, the bacterial contamination of blood waste.15 Blood product supply is a constant issue. In

462 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org most parts of the United States, fewer than 5% of management is a multidisciplinary approach based people who are eligible to donate actually do so, on reliable scientific evidence that focuses on indi- whereas the patient population that receives blood vidual patient needs and is a valuable tool not only most frequently (ie, the elderly) grows larger every in the surgical setting but is applicable in all stages year.15 of care and in any situation in which transfusions In the United States, approximately 15 million are commonly used or when significant blood loss units of packed RBCs per year are used during occurs.20 Patient blood management has three main surgical procedures.15 Interventions that are geared principles,21 “optimizing hematopoiesis, minimizing toward the reduction of bleeding and the use of bleeding and blood loss, and harnessing and opti- blood transfusions during surgery have become mizing physiological tolerance of anemia.”22(p58) a vital part of quality improvement programs. These goals can be met by the use of the follow- Patient blood management is defined as “the ing medical and surgical interventions to minimize scientific use of safe and effective medical and blood loss, maintain hemoglobin, and provide op- surgical techniques designed to conserve blood, timal hemostasis.16 prevent anemia, decrease bleeding, and optimize coagulation in an effort to improve patient out- Optimizing Hematopoiesis comes” (Figure 1).16 This principle involves identifying and treating Patient blood management is recognized as an any underlying anemias, optimizing erythropoiesis, important factor in positive patient outcomes by and using erythropoiesis stimulating agents. For several influential organizations, including The Joint example, surgeons can time a surgery so that it Commission,17 the US Department of Health and synchronizes with the patient’s best period of health Human Services,18 and the AABB.19 Patient blood and can correct nutritional anemia as well as use

Figure 1. The patient blood management matrix describes safe and effective medical and surgical techniques designed to conserve blood, prevent anemia, decrease bleeding, and optimize coagulation in an effort to improve patient outcomes. Reprinted with permission from the Society for the Advancement of Blood Management.

AORN Journal j 463 November 2013 Vol 98 No 5 OZAWA erythropoiesis-stimulating agent therapy and assess anemia be identified and treated before surgery, the patient for use of that can lead if possible. Anemia management protocols, in- to anemia (eg, angiotensin-converting enzyme cluding the use of iron and erythropoietic stimu- inhibitors).22 lating medications, increase the RBC mass in patients with anemia, thus reducing or eliminating Minimizing Blood Loss the need for allogeneic blood during surgery.7 In Health care providers should assess patients for addition, Boucher and Hannon7 suggest that pro- bleeding risks (eg, family history, past bleeding tocols are needed for discontinuing medications episodes); review medications that increase bleeding that may affect coagulation or increase bleeding, time and provide therapy if needed; and minimize such as warfarin, aspirin, clopidogrel, and certain blood loss during surgery as much as possible by herbal supplements. using meticulous hemostasis and surgical techniques, Before surgery, clinicians should screen patients blood sparing techniques (eg, acute normovolemic for a history of bleeding disorders (eg, hemophilia, hemodilution, cell salvage), and pharmacologic or von Willebrand disease). A preoperative family hemostatic agents. After surgery, caregivers can history and laboratory testing can help determine monitor and manage bleeding, maintain normo- whether these conditions exist and allow clinicians thermia, be aware of the adverse effects of medica- to plan for treatment. For example, recombinant tion on blood loss, and minimize iatrogenic blood coagulation factor VIIa (eg, NovoSevenÒ, Novo- loss (eg, postoperative blood loss from laboratory NordiskÒ) has been used in patients with severe testing).22 hemophilia A or B to induce hemostasis.25 Re- combinant coagulation factor VIIa works with the Managing Anemia body’s available tissue factors to induce the for- Health care providers can estimate potential blood mation of , which forms a stable, tight loss and identify what the patient can tolerate with- fibrin plug at the site of bleeding.26 Factor VIIa also out the use of blood products.22 Health care pro- has been used in patients undergoing cardiac sur- viders also can optimize the patient’s pulmonary gery when conventional hemostasis efforts have and cardiac function preoperatively, plan for blood failed.26 Factor VIIa is administered in doses of conservation techniques by using evidence-based 75 mg/kg to 100 mg/kg and is reported to cost up- strategies, and avoid or treat any infection.22 ward of $10,000 per dose.26 The efficacy of this therapy is variable, ranging from being no differ- PREOPERATIVE BLOOD MANAGEMENT ent than standard therapy to being associated with Preoperative anemia is a predictor of postopera- fatal cases of thromboembolism.26 A recent meta- tive morbidity and mortality.22 One of the most analysis showed that the use of factor VIIa in adult important tests for predicting transfusion needs is cardiac surgery patients resulted in no improve- the preoperative circulating erythrocyte mass, deter- ment in survival, and actually increased the risk of mined by a patient’s hemoglobin concentration.23 thromboembolism.25 According to the same study, According to the World Health Organization, factor VIIa use also failed to show improvement in anemia is defined as hemoglobin of <12 g/dL in the survival of patients undergoing trauma surgery, women and hemoglobin <13 g/dL in men compared but these patients did not show an increased risk of with the normal range for hemoglobin of 12.0 g/dL thromboembolism. to 15.5 g/dL in women and 13.5 g/dL to 17.5 g/dL in Factor VIII deficiency, also known as hemophilia men.24 Preoperative hemoglobin and coagulation A, is one of the most common hereditary bleeding status testing can facilitate the identification and disorders. Because some patients with hemophilia correction of anemia.7 Gombotz20 recommends that may be undiagnosed, clinicians routinely screen

464 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org patients for bleeding disorders and, if appropriate, and the patient’s hemodynamic status. As a result of can use a coagulation panel before surgery to test this fluid replacement, the blood lost during surgery for hemophilia A and other disorders. Patients then contains smaller amounts of RBCs because the can be treated with factor VIII both before and after blood has been diluted. By using the ANH tech- surgery to achieve and maintain adequate hemo- nique, the amount of RBCs lost during surgery is stasis.27 Prolonged factor VIII treatment lasting reduced. For example, a patient with a hematocrit several weeks is used in patients who have hemo- level of 45% who loses 1 L of blood would lose 450 philia and are undergoing bone and joint surgery to mL of RBCs; however, the same patient who is help ensure incision healing and to prevent bleeding treatedpreoperativelywithANHwouldhavea during postoperative physical therapy sessions.28 postoperative hematocrit level of only 25% and The cost of this therapy can be more than $50,000.27 would only lose 250 mL of RBCs. The blood pre- viously collected from the patient, along with PERIOPERATIVE BLOOD LOSS platelets, RBCs, and coagulation factors, is in- REDUCTION fused into the patient during or immediately after Perioperative blood loss is an important factor in surgery.30 Acute normovolemic hemodilution can 20 increased postoperative morbidity and mortality. be used in patients with normal hemoglobin and In addition to meticulous surgical technique, the hematocrit levels who are at risk of losing two or use of advanced, minimally invasive surgical tech- more units of blood during their surgical procedure. niques (eg, transcatheter, endoscopic, laparoscopic, Young, healthy adults are the best candidates, but robotic surgery techniques) may help decrease ANH also has been used successfully in geriatric 7 blood loss during surgery. During surgery, the and pediatric patients. Acute normovolemic hemo- surgical team can use various techniques to help dilution also has been used in patients undergoing decrease patients’ exposure to allogeneic blood, cardiac, orthopedic, vascular, and some general including intraoperative blood salvage, acute nor- surgical procedures.31 movolemic hemodilution (ANH), massive trans- fusion, and hemostatic agents. Massive Transfusion Hemorrhage often results in the need to transfuse Intraoperative Blood Salvage large volumes of blood and blood components. In certain types of procedures with a high expec- This is known as a massive transfusion. Health care tation of blood loss, a technique known as intra- teams often implement massive transfusion proto- 28 operative blood salvage may be used. This cols for patients for whom transfusion of more than technique consists of the surgical team collecting three units of blood occurs in a one-hour period the blood that the patient loses during surgery and further transfusions are likely. These blood- rather than discarding it. This blood is filtered and ordering protocols direct the administration of washed in a blood salvage and recovery device and certain amounts and types of blood products. Spe- 28 is returned to the patient. cific protocols, which often include algorithms and order sets, help clinicians determine the ratios of Acute Normovolemic Hemodilution blood components and their administration, and The ANH technique involves collecting a precal- differ among medical facilities.32 Effective patient culated amount of blood from the patient before blood management strategies can help minimize surgery and replacing it with an equal volume of these allogeneic transfusion needs. The collec- fluid.29 The volume of blood removed depends on tion and reinfusion of autologous blood in the the patient’s initial hematocrit levels, the blood perioperative period can reduce the amount of volume estimated to be lost during the surgery, allogeneic units needed, reduce the patient’s blood

AORN Journal j 465 November 2013 Vol 98 No 5 OZAWA product exposure, and reduce the effect of a mas- to 10.0 g/dL. This transfusion trigger continues to sive transfusion on both the regional and local be standard practice despite evidence that lower blood supply.2 hemoglobin levels can be safely tolerated.5 Clinical trials have shown that a more conservative trans- Hemostatic Agents fusion trigger (ie, a hemoglobin level of 7.0 g/dL Pharmacological agents and topical hemostatic to9.0g/dL)wasassafeasahighertransfusion agents and sealants also can be used to minimize trigger (ie, a hemoglobin level 10.0 g/dL to 12.0 blood loss and can be essential to help minimize g/dL) in critical care patients. These patients showed intraoperative blood loss and to achieve optimal similar mortality rates, lower intensive care and patient outcomes. When an appropriate combina- hospital lengths of stay, and lower rates of multiple tion of therapies is used, blood loss and allogeneic organ dysfunction.36,37 Patients with ischemic car- blood transfusion can be greatly reduced.33 diovascular disease are the exception to this finding, and they exhibit slightly lower, but nonsignificant, POSTOPERATIVE MANAGEMENT survival rates by using a restrictive transfusion Methods for managing patients in the postopera- strategy.34 tive period include close monitoring for bleeding, Evidence from surgical patients who uniformly avoiding hypertension, tolerating normovolemic refuse blood transfusions demonstrates that patients patient anemia, and managing anticoagulant and with extremely low hemoglobin levels can survive antiplatelet drugs.34 If anemia develops postoper- without complications.20 One recent study com- atively, it must be managed. Another postoperative pared the morbidity and long-term survival of consideration is to address phlebotomy-induced patients who underwent cardiac surgery and re- blood loss. fused blood transfusions with a similar group of patients who received transfusions.38 Nontrans- Postoperative Anemia fused patients had better one-year survival rates, Anemia is a common occurrence after major sur- shorter hospital stays, and fewer acute complica- gery and can be partially attributed to the amount tions than the patients who received transfusions, of blood lost intraoperatively and postoperatively and the long-term survival rate was similar between as well as the presence of anemia in the preopera- the two groups.38 tive period.35 However, the development of post- operative anemia is a more complex phenomenon. Phlebotomy After surgery, the release of inflammatory cyto- Another common issue in postoperative patients is kines leads to decreased gastrointestinal uptake of phlebotomy-induced blood loss. Motivated nurses, iron and the sequestration of iron in macrophages, physicians, and other health care professionals can which could result in iron deficiency and anemia.35 help decrease the need for transfusions by using Decreased erythropoietin production and decreased simple, low-cost strategies aimed at decreasing response to erythropoietin leads to decreased RBC blood loss. One strategy is to minimize blood loss production.35 Treatment for postoperative anemia secondary to diagnostic phlebotomy, especially in 7 can include iron supplements and erythropoietic critical care patients. Losses in the range of 41 mL stimulating agents. Allogeneic blood transfusions to 65 mL of blood per day have been reported in the only should be considered when no alternative is medical literature and have been associated with 29 suitable and when the potential benefits outweigh the development of anemia. Phlebotomy blood the associated risks.21 loss can be reduced by using strategies that include Historically, clinicians have used a “transfusion n eliminating the procedure of arterial line blood trigger” of a hemoglobin level less than or equal discard,

466 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org n using small volume (ie, pediatric size) blood gelatins and collagens; and combined agents.42 collection tubes, and Hemostatic agents are used to stop bleeding in n ordering laboratory tests only when clinically the presence of actively flowing blood when ap- justified.30 plied directly to the bleeding site. Tissue sealants are used to close and bind tissue defects.43 These THE ROLE OF TOPICAL HEMOSTATIC AND products are applied to dry or clamped tissue sur- SEALANT AGENTS faces, creating a barrier to prevent leaking at the Effective hemostasis has been shown to decrease surgical site.43 They are safe and effective, but the morbidity and mortality associated with sur- many differences exist between products, and gical procedures.5 The fast and effective minimi- nurses must be knowledgeable about the differ- zation of intraoperative bleeding plays an integral ences, because they can determine product efficacy role in an effective blood management program. in various bleeding scenarios encountered during Intraoperative blood loss also increases exposure to surgery. An overview of these products can be blood transfusions and their associated risks.39-41 found in Table 1. Blood transfusion has been shown to be an inde- pendent risk factor for intensive care unit admission Single-Component Hemostatic Agents and for infection and respiratory complications after This class of products has existed since the surgery. Patients who received more than two units 1940s. The products have no intrinsic hemostatic of blood had double the rate of intensive care unit action; they simply provide mechanical hemostasis admissions and twice the risk of postoperative in- via a physical matrix in which platelets can ag- fectious and respiratory complications than patients gregate and clotting can occur at the site of who did not receive more than two units of blood.41 bleeding.33 These products help hemostasis of mi- Perioperative bleeding that clinicians believe nor bleeding from venules and capillaries, and in requires blood transfusion is common during car- situations in which there is generalized oozing diac surgery, with as many as 50% of patients being of blood. The surgeon applies these agents to the transfused, and these procedures consume as much bleeding site, then either removes the products after as 10% to 31% of the nation’s blood supply.31 Be- achieving hemostasis or leaves them in place to cause the control of bleeding and sealing of opera- biodegrade and absorb over time. The time it takes tive surfaces by sutures or cautery is not always for these topical agents to be absorbed varies and is effective or practical, a variety of topical agents influenced by the amount used, the site of appli- have been developed that supplement local hemo- cation, and the local environment (eg, the pH of the stasis and limit bleeding in the surgical wound. The surrounding tissue). Generally, total absorption can Blood Conservation Clinical Practice Guidelines take anywhere from weeks to months.43 developed by the Society of Thoracic Surgeons state Formulations and methods of application for that “these topical hemostatics may be considered to these passive topical hemostatic agents vary widely, provide local hemostasis as part of a multimodality and choosing the correct product plays an important blood management program.”31(p 965) role in the product’s effectiveness.39 These products Topical hemostatic and sealant agents are im- include portant adjunctive tools to assist in blood conser- vation, and these agents can help decrease overall n porcine gelatin (eg, GelfoamÒ, SurgifoamÒ), procedure time and hasten patient recovery.41 n cellulose (eg, SurgicelÒ, Surgicel Nu-KnitÒ), Topical hemostatic and sealant agents include n bovine collagen (eg, AviteneÒ sheets, biologically active topical hemostats, for example, UltrafoamÒ collagen sponges), and thrombin; absorbable hemostats, which contain n polysaccharide spheres (eg, AristaÒ).33

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j TABLE 1. Hemostatic Agents and Sealants ONJournal AORN

Hemostatic agents Sealants Single- component Combination hemostats hemostats Thrombin Fibrin-based Synthetic Fibrin-based Other

Component Collagen Collagen or gelatin Bovine Thrombin þ Polyethylene Thrombin þ Animal protein Gelatin þ thrombin with Human fibrinogen with or glycol polymers10 fibrinogen with or hydrogel1 Cellulose1 or without the Recombinant without fibrinolysis without fibrinolysis patient’s plasma2-4 human5-7 inhibitor8,9 inhibitor8

Mechanism of Contact activation Contact activation conver- Replication of final Covalent and Replication of final action with or without þ fibrinogen con- sion to fibrin stage of clotting mechanical stage of clotting platelet version to fibrin1 Activation of platelet cascade1,8,11 bonding8 cascade1,8,11 aggregation1 aggregation1

Coagulation Intact1 Intact through Intact through Intact through Independent Intact through status coagulopathic1 coagulopathic 11 coagulopathic1 of coagulation coagulopathic1 cascade12

Uses Capillary oozing Capillary oozing Capillary oozing Capillary oozing High-pressure Prevent leakage Arteriolar bleeding1 Arteriolar bleeding2,3 Minor bleeding11 Arteriolar bleeding8,9 sealing12 ,13 from colonic Oozing to spurting4 anastomoses after reversal of a temporary colostomy8

Contraindications Sensitivity to the Sensitivity to the Sensitivity to the Sensitivity to the Not for Sensitivity to Bovine allergy1 product’s product’s product’s product’s intravascular aprotinin8 No intravascular or ingredients1 ingredients2-4 ingredients5-7 ingredients8,9,11 use12 No direct injection cerebrovascular Should not be No intravascular No direct injection No direct injection into circulatory use1 used on skin use2-4 into circulatory into circulatory system or highly Do not apply directly closure incisions2 Do not use on skin system or highly system or highly vascularized to phrenic nerve or 2-4 8 1

Do not place in closure incisions vascularized vascularized tissue the heart OZAWA intravascular Do not use when the tissue5-7 tissue8,9,11 Not for sever venous compartments1 vessel is clamped or arterial or bypassed2-4 bleeding8 AIN LO MANAGEMENT BLOOD PATIENT TABLE 1. (continued) Hemostatic Agents and Sealants

Hemostatic agents Sealants Single- component Combination hemostats hemostats Thrombin Fibrin-based Synthetic Fibrin-based Other

Do not use in the Do not use for Do not use for severe presence of massive arterial venous or arterial infection2-4 bleeding5-7 bleeding8,9,11 Do not use in presence of infection5-7

Products GelfoamÒ FloSealÒ Thrombin-JMIÒ TisseelÒ CoSealTM TisseelÒ BioGlueÒ SurgicelÒ D-statÒ EvithromÒ EvicelÒ SurgiFloÒ VitagelÒ RecothromÒ TachoSilÒ INSTATÒ Thrombi-GelÒ HemoStaseTM AviteneÒ HeliteneÒ HelistatÒ

Gelfoam, Tisseel, and FloSeal are registered trademarks and CoSeal is a trademark of Baxter International, Deerfield IL. Surgicel, SurgiFlo, INSTAT, Evithrom, and Evicel are registered trademarks of Ethicon Inc, a subsidiary of Johnson & Johnson, Somerville, NJ. HemoStase is a trademark of Cryolife, Auckland, New Zealand. Avitene is a registered trademark of Davol, Inc, a subsidiary of CR Bard, Inc, Providence, RI. Helitene and Helistat are registered trademarks of Integra, Plainsboro, NJ. D-stat flowable hemostat is a registered trademark of Vascular Solutions Inc, Minneapolis, MN. Vitagel is a registered trademark of Medafor, Minneapolis, MN. Thrombi-Gel and Thrombin-JMI are registered trademarks of Pfizer, Inc, Peapack, NJ. Recothrom is a registered trademark of ZymoGenetics, a subsidiary of Bristol Myers Squibb, Seattle, WA. TachoSil is a registered trademark of Takeda Pharmaceuticals International, a subsidiary of Baxter International, Zurich, Switzerland. BioGlue a registered trademark and HemoStase is a trademark of CryoLife, Inc, Kennesaw, GA. 1. Gabay M. Absorbable hemostatic agents. Am J Health-Syst Pharm. 2006;63(11):1244-1253. 2. FloSeal hemostatic matrix instructions for use. Baxter Biosurgery. http://www.floseal.com/us/preparation.html. Accessed June 19, 2013. 3. D-Stat flowable hemostat instructions for use. Vascular Solutions, Inc. http://www.accessdata.fda.gov/cdrh_docs/pdf/P990037S024c.pdf. Accessed June 19, 2013. 4. Vitagel Surgical Hemostat instructions for use. Orthovita. http://www.orthovita.com/pdfs/Vitagel_Brochure.pdf. Accessed June 19, 2013. 5. Product fact sheet: Thrombin-JMIÒ syringe spray kit (thrombin, topical, bovine origin, USP). Pfizer Injectables. http://www.pfizerinjectables.com/factsheets/Thrombin-JMI_all%20SKUs.pdf. Accessed June 19, 2013. ONJournal AORN 6. EvithromÒ. Ethicon360. http://www.ethicon360.com/products/evithrom-thrombin-topical-human. Accessed June 19, 2013. www.aornjournal.org 7. RecothromÒ. Global Health Science Center. http://www.recothrom.com/. Accessed June 19, 2013. 8. Lawson JH. The clinical use and immunologic impact of thrombin in surgery. Semin Thromb Hemost. 2006;32(1):98-110. 9. TisseelÒ fibrin sealant. Baxter Healthcare. http://www.tisseel.com/us/preparation_use.html. Accessed June 19, 2013. 10. EvicelÒ fibrin sealant (human). Ethicon360. http://www.ethicon360.com/products/evicel-fibrin-sealant-human. Accessed June 19, 2013. 11. CoSeal [surgical sealant]. Baxter Healthcare. http://www.baxterhealthcare.com.au/downloads/healthcare_professionals/cmi_pi/coseal_pi.pdf. Accessed June 19, 2013.

j 12. Coseal mechanism of action. Baxter Healthcare. http://www.coseal.com/int/coseal-mechanism-of-action.html. Accessed June 19, 2013.

469 13. How COSEAL surgical sealant works. Coseal Surgical Sealant. http://www.coseal.com/int/coseal-mechanismof-action.html. Accessed June 19, 2013. November 2013 Vol 98 No 5 OZAWA

This class of hemostats relies on the patient’s own factor V as well as some of the other proteins found circulating coagulation factors to achieve hemo- in these preparations. Secondary exposure to bo- stasis, so they are only appropriate for patients who vine thrombin during surgery has been known to have an intact coagulation cascade.44 These products cause an immunologic response, and the resultant are typically used as first-line agents in many types changes in normal hemostasis can lead to post- of surgeries because of their immediate availability operative adverse events, such as anaphylactic and low associated costs.45 They are considered to reactions, life threatening bleeding, and death.46 be most useful in situations of minimal bleeding.45 Because of these risks, bovine thrombin carries a Thrombin is a hemostatic agent that also has been black box warning.47 A black box warning is the available for many years. Descriptions of thrombin strongest warning required by the US Food and use were cited in the European literature as early as Drug Administration for prescription medications 1892, and reports of thrombin’s use in surgery can that are considered to be high risk and can be found be found as far back as the 1940s.46 Thrombin is in the package insert or on the package itself. Black a biologically active topical hemostatic agent that box warnings alert prescribers of reports in the reacts with the patient’s own circulating fibrino- medical literature showing a significant risk of gen at the site of bleeding, stimulating coagulation serious and potentially fatal adverse effects.50 cascade activity and promoting the conversion of Human thrombin is derived from the pooled fibrinogen to fibrin to produce a fibrin clot.45 Unlike plasma of human donors. It was developed to help passive agents, this active agent can be effective in minimize the risks of bovine thrombin. There is low-level bleeding in patients with impaired coag- a small potential for transmitting bloodborne path- ulation systems, and thrombin is indicated for aid- ogens via human thrombin; however, plasma donors ing hemostasis in cases of oozing blood and minor are screened for previous virus exposure to help bleeding originating from accessible venules and mitigate the risk of infection transmission.48 Pooled capillaries.47-49 plasma is tested for the presence of certain viruses, There are currently three types of thrombin agents for example, hepatitis and, if viruses are present, used in surgery: bovine thrombin (eg, Thrombin- they are inactivated and removed during manu- JMIÒ), pooled human plasma thrombin, and re- facturing.48 Pooled human thrombin is a human combinant thrombin (eg, RecothromÒ). Despite plasma derivative available in both liquid and having similar efficacy, individual thrombin prod- powder preparations. ucts differ significantly in terms of potential com- Another topical thrombin formulation, recombi- plications.47-49 Thrombin comes in a powder form nant human thrombin, is derived from hamster or that can be reconstituted with saline solution when snake proteins. This formulation provides a manu- needed for use, and its recommended storage is in factured thrombin product without the risk of the controlled room temperature.47 antibody development caused by bovine thrombin The first commercially available thrombin was and without the theoretical risk of the transmission bovine in origin and is the most common thrombin of human viruses associated with human-derived product currently marketed in the United States. thrombin. Recombinant human thrombin is avail- This type of thrombin may cause a delayed im- able as a powder and can be stored at room tem- munologic response, which may occur from re- perature.49 It can cause allergic reactions in patients exposure to the product during subsequent surgical who are allergic to hamsters or snake proteins procedures and can cause significantly disordered because it is produced by using cells from these coagulation function.47 Patients who have been animals.49 exposed to bovine thrombin may be at risk for All types of thrombin can be used in a variety of the development of antibodies to the product and ways to provide hemostasis during surgery. It can

470 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org be used as a stand-alone agent, be combined with an FloSealÒ is composed of bovine gelatin gran- absorbable hemostat, or be used in a manufactured ules designed to be combined with the provided fibrinogen-thrombin combination. The choice of human pooled plasma thrombin and calcium chlo- whether to use a thrombin or a combination prod- ride. On contact with blood, the gelatin particles uct is primarily based on the surgeon’s preference. swell 10% to 20% to gently tamponade bleeding, Thrombin spray can be used for hemostasis in cases while the high thrombin concentration in and of minor bleeding from large raw surfaces. Com- around the granules combines with the patient’s binations of gelatin and thrombin aids hemostasis fibrinogen to form a mechanically stable clot. It in neurosurgery and vascular procedures. Fibrin works at both ends of the coagulation cascade and glues are commonly used for many different sur- is not compromised by most clotting cascade defi- gical procedures.51 Because these products have ciencies. Therefore, it has shown efficacy even in different safety profiles, it is important for clinicians patients who are fully heparinized.55 FloSeal is to be aware of both the source of thrombin (ie, bo- used in surgical procedures as an adjunct to hemo- vine, human, recombinant) and any additives that stasis when control of bleeding by other conven- may be found in the manufactured preparations. tional procedures is found to be either ineffective The perioperative nurse should assess the patient or impractical.53 FloSeal can be applied to either frequently for reactions during and immediately hard or soft tissue. It works on actively bleeding after the surgical procedure and clearly document tissue and can conform to the shape of irregular the administration of any thrombin agents.52 wound surfaces. This product controls bleeding that ranges from oozing to spurting and can be applied Combination Hemostatic Agents either focally or spread to cover larger areas of Combination products provide both a mechanical diffuse bleeding. FloSeal is absorbed by the body and an active hemostat in a single product.53,54 They six to eight weeks after application, consistent with contain collagen or gelatin in combination with wound healing.53 human or bovine thrombin. Combination hemo- VitagelÒ contains bovine thrombin and bovine static agents stop bleeding by two different mech- collagen, which are used in combination with the anisms, contact activation and platelet aggregation. patient’s own plasma.56 During the surgical pro- Platelet aggregation is caused by the direct effect cedure, 10 mL of the patient’s blood is collected of the collagen product’s contact with blood. These and centrifuged, and the plasma is collected. This products are used as adjunct treatments to control plasma is then placed in the Vitagel dual-syringe many types of surgical bleeding from oozing to system, where it combines with the thrombin and spurting bleeding. Indications for these agents vary collagen during application. The bovine thrombin widely among the different available products. portion of Vitagel converts the patient’s fibrin- SurgifloÒ is a porcine gelatin matrix that is used ogen to fibrin in the presence of collagen. This in combination with bovine or other . forms a collagen-fibrin gel matrix that conforms Surgiflo is available as a sterile, absorbable gelatin to the bleeding site. It is believed that the platelets paste of porcine origin.54 It is applied directly to the from the patient’s plasma provide growth fac- bleeding surface. The gelatin paste is available as a tors and improve the strength of the clot.57 The prefilled syringe that is intended to be mixed with product is resorbed within 30 days and is indi- 2 mL of liquid (eg, sterile saline solution, throm- cated as an adjunct to hemostasis when bleeding bin). The hemostatic matrix kit with thrombin adds cannot be controlled by conventional methods. human thrombin. The desired consistency can be This product is not indicated for use in neuro- achieved by controlling the amount of saline solu- surgical or ophthalmic procedures, but it has tion or thrombin used.54 proven to be effective for bleeding during general,

AORN Journal j 471 November 2013 Vol 98 No 5 OZAWA hepatic, cardiac, and orthopedic surgical randomized trial compared the use of fibrin sealant procedures.56 versus stand-alone topical hemostatic agents (eg, Avitene, Gelfoam, OmnicellÒ, Surgicel, bovine Fibrin Sealants thrombin) in patients who underwent emergency Fibrin sealants combine high concentrations of sternotomy. Results showed significantly faster human fibrinogen with human, bovine, or recom- bleeding control, along with decreased postopera- binant thrombin.45 Some products also contain tive blood loss in the patients who were treated , an antifibrinolytic agent, to help maintain with the fibrin sealant.57 Fibrin sealants are par- a stable fibrin clot. Calcium chloride is also found ticularly useful in patients with clotting disorders in some products, acting as a cofactor for coagu- and for use in minimally invasive surgery.60 lation proteins. In contrast to the absorbable he- Several fibrin sealant products are approved by mostatic agents, the fibrin-based sealants exert the US Food and Drug Administration and are their effect at the end of the coagulation cascade, currently in use in the United States. Both TisseelÒ mimicking the final stage of coagulation.43 In the and EvicelÒ are indicated as aids to hemostasis in presence of thrombin and calcium, fibrinogen is surgical patients whose bleeding cannot be con- converted to fibrin, and factor XIII is also activated trolled by conventional surgical techniques, such by thrombin, stabilizing the clot.55 These products as cautery, suture, and ligature.62,63 Both products allow for faster clot formation than would occur have dual-syringe delivery systems that combine during the patient’s natural coagulation cascade and the two components immediately before applica- bring 15 to 25 times higher physiological fibrinogen tion. Tisseel, the first fibrin sealant to receive US concentrations to the bleeding site than are found Food and Drug Administration approval, in 1998, in circulating plasma.58 This process occurs inde- is made from human fibrinogen and thrombin from pendently of the other parts of the coagulation pooled donors as well as aprotinin to prevent pre- cascade, making these products useful in patients mature breakdown of the clot. It is effective in with defects in other parts of the pathway.43 Fibrin patients who have been treated with heparin. Tis- sealants serve as a primary hemostatic plug and as seel is currently available in a prefilled syringe that a matrix to enhance wound healing.59 The relative must be thawed or warmed for five to 12 minutes concentration of thrombin determines the rapidity before use.62 Evicel incorporates human pooled of clot formation, and the fibrinogen concentration plasma thrombin and human pooled fibrinogen. It determines the mechanical strength of the fibrin is also available in a syringe that is required to sealant.57 These products are not associated with be thawed or warmed for 10 minutes before use.62 inflammation, foreign body reactions, tissue ne- TachoSilÒ is a ready-to-use hemostatic patch crosis, or extensive fibrosis because the fibrin clot that consists of an equine-based collagen pad is reabsorbed within 14 days in the course of the coated with human fibrinogen and human throm- normal wound healing process.60 bin.64 TachoSil reacts when in contact with bodily Fibrin sealants provide clinicians with several fluids, blood, or saline solution to form a clot that advantages over other forms of hemostasis. Fibrin adheres to the tissue surface. Hemostasis occurs sealants can be applied to tiny blood vessels and within minutes, and the TachoSil patch is absor- to places that are unable to be reached by con- bed during the body’s natural healing process ventional sutures. They form a stable clot more within several weeks. There have been rare reports rapidly, help decrease surgical blood loss, de- of hypersensitivity or allergic reactions second- crease the probability of postoperative infection ary to TachoSil use.64 Patients who are allergic or inflammation, and are absorbed by the body as may experience severe hypersensitive reactions. part of its natural healing process.61 A prospective, Patients who are allergic or intolerant to horse

472 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org proteins or human blood products should not use create a flexible mechanical seal. BioGlue starts TachoSil.64 to polymerize in approximately 20 to 30 seconds, and full strength bonding occurs within two minutes. Synthetic Surgical Sealants It also sticks to synthetic graft materials by mechan- Sealants create a barrier that can prevent leakage. ical interlocks within the graft matrix. BioGlue is They can be applied both to dry or clamped tissue useful in a wide variety of cardiac reconstruction surfaces. These agents do not themselves function as procedures. It is approved for use in adults as an hemostats, but when applied and allowed to poly- adjunct to standard hemostasis methods, such as merize, create a mechanical barrier to bleeding. staples and sutures, in open surgical repair of large Synthetic sealants are composed of different com- blood vessels (eg, the aorta, carotid, or femoral binations of polyethylene glycols plus a second arteries).67 The BioGlue product labeling contains component, such as sodium phosphate/carbonate a black box warning advising that the product not be trilysine amine. These products are completely applied directly to the phrenic nerve or directly to synthetic and avoid the risk of patient hypersensi- the surface of the heart because of the potential for tivities as opposed to other sealants that contain serious, life-threatening tissue necrosis.54 bovine components or glutaraldehyde, which may trigger hypersensitivities. The synthetic sealants are PRODUCT SELECTION also naturally absorbed within four to eight weeks Proper selection of appropriate hemostatic and after application.62,64 sealant agents can greatly influence clinical out- CoSealTM consists of two solutions, one being comes. Their use is determined based on the specific a high molecular weight polyethylene glycol solu- clinical situation and is influenced by wound size and tion and the other a sodium phosphate/sodium configuration, severity of bleeding, surgical access carbonate buffer that can be focally applied or to the bleeding site, and the coagulation function of sprayed onto tissue.65 These two components the patient, and by whether the bleeding is the result crosslink to form a hydrogel matrix that chemi- of a singular surgical procedure or after repeated cally (ie, covalently) binds to tissue proteins or surgical procedures.52 Frequent, good communica- mechanically bonds to synthetic graft materials.66 tion between the nurse and the surgeon at the be- As with the absorbable hemostats, CoSeal can ginning and throughout the procedure regarding swell up to four times its original volume after the amount and site of hemorrhage, the patient’s application and should be used cautiously around current coagulation function, and product selection anatomical structures that may be sensitive to are crucial to successful outcomes.52 compression. CoSeal is very effective in vascular Clinicians also must consider specific religious or cardiac surgery but only in situations for which and cultural factors that affect the choice of topical expansion or swelling are not a concern. The main hemostatic agents. Different topical hemostatic advantages of CoSeal are that it is transparent and agents are derived from different sources or com- flexible and that it achieves rapid hemostatis.57 binations of sources. They may be derived from BioGlueÒ is a bovine serum albumin and glu- plant, human, equine, bovine, or porcine sources; taraldehyde surgical adhesive.67 The two separate may be synthetically derived; or may be a combi- solutions are held in a double-chambered syringe nation of several sources, depending on the indi- and mix in the applicator tip at the time of applica- vidual product. Patients who decline blood for tion. The bovine serum albumin molecules cov- religious reasons also may refuse the use of agents alently bond to one another and also bond to tissue that have factors derived from human or animal proteins at the site of repair. BioGlue works inde- plasma, and some patients may refuse agents that pendently of the body’s clotting mechanism to have factors derived from a specific animal. For

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TABLE 2. The Perioperative Nurse’s Role in Patient Blood Management1

Patient blood management standard Perioperative nurse’s role

Health care facilities should have a patient blood management Develop and implement educational programs that define program with a defined “scope of service, mission, vision individual roles in patient blood management, gain support, and values, policies and procedures, clinical protocols, and review the tools available. Develop and deliver educa- educational programs for health care providers, and review tional programs outlining the risks and benefits of trans- of patient outcomes.”1(p3) fusions and the alternative treatments currently available.

Health care providers should have a facility-provided, well- Develop standardized and enduring patient education mate- defined, and consistent informed consent process for rials to assist caregivers in explaining the risks and benefits administering blood and blood products and for “obtaining of transfusion consistent with the patient’s level of under- an advance directive from patients who decline transfusion standing, as well as available transfusion alternatives. for religious or other reasons.”1(p5)

Health care providers should be appropriately educated and Develop and implement ongoing education and training that competent to administer blood and blood products in outlines procedures for the safe and appropriate adminis- a safe manner.1 tration of blood products.

Health care facilities should have a process in place that Review the utilization and availability of perioperative anemia periodically evaluates the effectiveness of their patient blood management. Evaluate patient outcomes related to peri- management program.1 operative diagnosis and treatment of anemia, collection and reinfusion of autologous blood, and the use of drug therapy to treat and prevent anemia, including iron and erythropoietin.

Health care facilities should have a process to identify and Screen patients for anemia and recommend laboratory testing manage patients with preoperative anemia who are to determine its cause. scheduled for surgery with a risk of blood loss that might require red blood cell transfusion.1

Health care providers should “collect, process, and reinfuse Develop and implement training and ongoing competency shed autologous blood or extracorporeal blood from assessments about autologous blood collection and patients in the perioperative period,”1(p13) reduce blood loss reinfusion to minimize complication. and allogeneic blood transfusion.

Health care facilities should have a standardized method for Educate staff members on the complications of acute nor- performing acute normovolemic hemodilution in patients movolemic hemodilution so that if complications occur, they undergoing surgery during which “the blood loss is antici- may be promptly recognized and addressed. pated to exceed 15% of the patient’s blood volume.”1(p16)

Health care facilities should have written guidelines for mini- Educate staff members on the need to reduce phlebotomy mizing blood loss from postoperative phlebotomy for blood loss. Eliminate the collection of extra blood tubes in diagnostic laboratory testing.1 anticipation of future laboratory testing.

There should be cooperation among facility personnel (eg, the Identify those patients who are at increased risk for blood blood management program director, pharmacy, surgery, loss. Screen patients for the use of anticoagulant or anesthesia and transfusion service/blood bank) to minimize antithrombotic medications to mitigate the risk of bleeding a patient’s blood loss associated during surgery, interven- from these agents. Provide education on therapies such as tional procedures, and from underlying clinical conditions.1 topical hemostatic agents, tissue adhesives, and other technologies to reduce incision blood loss.

474 j AORN Journal PATIENT BLOOD MANAGEMENT www.aornjournal.org

TABLE 2. (continued) The Perioperative Nurse’s Role in Patient Blood Management1

Patient blood management standard Perioperative nurse’s role

Health care facilities should have a written protocol for the Institute policies, procedures, and training programs to help management of patients who experience transfusion after rapidly identify those patients who are at risk of needing large volume blood loss and hemodynamic instability.1 massive transfusions.

Health care facilities should have and implement a compre- Develop and implement transfusion guidelines. Develop hensive, written, evidence-based guideline for transfusion of comprehensive order sets for transfusions and provide staff blood products.1 member education on the use of these tools.

Health care providers should identify and manage patients at Review laboratory tests and clinical history for information on risk for transfusion from anemia or for developing anemia possible risk factors and causes of anemia. during the course of hospitalization to reduce their need for transfusion.1

1. Administrative and Clinical Standards for Patient Blood Management Programs. 2nd ed. Englewood, NJ: Society for the Advancement of Blood Management; 2013. http://www.sabm.org/publications. Accessed June 19, 2013.

example, people of the Hindu belief system may THE NURSE’S ROLE IN PATIENT BLOOD be opposed to bovine-derived products, and those MANAGEMENT practicing Orthodox Judaism may refuse porcine- Nurses play a vital role in promoting evidence-based derived products. Health care professionals and practices and in optimizing patient blood manage- patients should be educated on the possibility that ment. Many facilities incorporate evidence-based these types of products may be needed, and care- care models, the development of multidisciplinary givers should assess the patient’s stance on the care teams, and the establishment of professional acceptability of their use and document the pa- accountability. Although it is primarily a medical tient’s acceptance or refusal well ahead of the responsibility to prescribe blood components, the surgical intervention whenever possible. Health responsibility for performing a transfusion most care professionals need to take an individualized often falls on primary care nurses. There are several approach to the use of these products to determine negative statistics that can be cited related direct- the right fit for each patient. ly to the transfusion process. For example, in the The “Recommended practices for product selec- United States, ABO transfusion errors are the cause tion in perioperative practice settings”68 provides of more noninfectious transfusion deaths annually a useful guideline for product selection, and it in- than any other cause. It is estimated that one in cludes recommendations for a multidisciplinary 12,000 to one in 19,000 transfusions are adminis- approach to the evaluation and selection of products tered to the wrong patient.69,70 These transfusion such as hemostats and sealants. These guidelines errors also include phlebotomy and blood bank er- address many factors, including evidence-based rors that include the testing of the wrong specimen. practice, financial effects of product selection, stor- The failure to detect the potential transfusion of the age challenges, and facility standardization. The wrong unit of blood at the bedside continues to be AORN document68 also highlights the integral po- an important source of transfusion error.68 These sition that perioperative RNs have as end users of statistics demonstrate the seriousness and potential OR products, and how nurses’ expertise and insight harm of this common medical intervention carried are an invaluable resource in product selection.68 out by nurses.68

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Primary-care nurses are on the front lines of Nordisk, Inc, Plainsboro, NJ. Gelfoam, FloSeal, patient care and can play a key role in implementing and Tisseel are registered trademarks and CoSeal effective patient blood management strategies that is a trademark of Baxter International, Deerfield, result in decreasing or eliminating a patient’s ex- IL. Surgifoam, Surgicel, Surgicel Nu-Kit, SurgiFlo, posure to allogeneic blood. Suggestions for how the and Evicel are registered trademarks of Ethicon, perioperative nurse can incorporate patient blood Inc, a subsidiary of Johnson & Johnson, Somer- management into all phases of care are listed in ville, NJ. Avitene and Ultrafoam are trademarks Table 2. For example, the existence of preoperative of Davol, Inc, a subsidiary of CR Bard, Inc, anemia is often detected by nurses in the presurgical Providence, RI. Arista-AH and Vitagel are regis- setting. Nurses also play a vital role in reducing tered trademarks of Medafor, Minneapolis, MN. hospital-acquired anemia, which is widespread.71 Thrombin-JMI is a registered trademark of Pfizer, Nurses can advocate for patient safety by fa- Inc, Peapack, NJ. Recothrom is a registered trade- miliarizing themselves with the evidence-based mark of ZymoGenetics, a subsidiary of Bristol indicators for blood product transfusion. Nonprofit Myers Squibb, Seattle, WA. Omnicell is a registered professional organizations, such as the Society for trademark of the Omnicell Corporation, Mountain the Advancement of Blood Management, provide View, CA. TachoSil is a registered trademark of educational resources for nurses, physicians, and Takeda Pharmaceuticals International, a subsid- patients. In addition, nurses play a fundamental iary of Baxter International, Zurich, Switzerland. role in educating patients about issues related to BioGlue is a registered trademark of CryoLife, Inc, blood transfusion and the many modalities avail- Kennesaw, GA. able for patient blood management. Nurses have AORN does not endorse any commercial com- the opportunity to create policies and procedures, pany’s products or services. Although any com- construct and implement nursing practices, and mercial products that may be referenced in this develop and provide staff education to promote material are expected to conform to professional effective and safe patient blood management.72 medical/nursing standards, inclusion of this mate- CONCLUSION rial does not constitute a guarantee or endorsement Intraoperative bleeding can be life threatening, and by AORN of the quality or value of such product or the fast, efficacious blood management planning that of the claims made by its manufacturer. incorporates the use of topical hemostatic agents References plays an essential role in optimizing patient out- 1. Starr D. Blood an Epic History of Medicine and Com- comes. The fast and effective minimization of in- merce. 2nd ed. New York, NY: Harper Collins; 20023-17. 2. Administrative and Clinical Standards for Patient Blood traoperative bleeding plays an integral role in an Management Programs. Englewood, NJ: Society for the effective blood management program. In the area Advancement of Blood Management; 2012. of intraoperative hemostasis, a perioperative nurse’s 3. Scheurer DB, Roy CL, McGurk S, Kachalia A. Effec- tiveness of computerized physician order entry with knowledge and familiarity with the wide variety of decision support to reduce inappropriate blood trans- available hemostatic agents can be invaluable to the fusions. J Clin Outcomes Manage. 2010;17(1):17-26. 4. Shander A, Fink A, Javidroozi M, et al. Appropriateness surgical team. of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes. Transfus Acknowledgment: The author thanks Maria Ashton, Med Rev. 2011;25(3):232-246. MBA, MS, RPH, for her medical writing and 5. Marik PE, Corwin HL. Efficacy of red blood cell trans- fusion in the critically ill: a systematic review of the assistance in the development of this manuscript. literature. Crit Care Med. 2008;36(9):2667-2674. 6. Renkens KL Jr, Payner TD, Leipzig TJ, et al. A multi- ’ center, prospective, randomized trial evaluating a new Editor s notes: NovoSeven and NovoNordisk are hemostatic agent for spinal surgery. Spine (Phila Pa registered trademarks of Novo Nordisk A/S, Novo 1976). 2001;26(15):1645-1650.

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