- Email: [email protected]
Patient Blood Management
CHAPTER 59
Patient Blood Management Ruchika Goel, MD, MPH and Patricia A. Shi, MD Patient blood management (PBM) is the term given to the appropriate use of blood transfusion to optimize patient care. Patient-centric approach is its core principle (Fig. 59.1). PBM is “transfusing the right product in the right dose to the right patient at the right time for the right reason.” PBM has five main tenets (Fig. 59.2). In addition to improving patient safety, PBM programs decrease hospital costs and conserve clinical resources. Cost can range from $522–1183/RBC unit when accounting for storage, testing, and labor.
Implementing Blood Management Program: Hospital-wide, comprehensive, and multidisciplinary PBM program can optimize patient care, avoid unnecessary transfusions of blood products, and limit adverse effects. Successful PBM programs are rooted in evidence-based medicine and enhance patient safety and outcomes through
Optimization Of Red Cell Mass Pre-op Anemia Management
Multi-disciplinary Blood Conservation Strategies
Patient Centered Approach of all PBM Tenets
Optimizing Coagulation and Improved Hemostasis
Patient Centered And Evidence Based Clinical Decision Making
FIGURE 59.1 Key principles of patient blood management. (Adapted from Society of Blood Management 2012 learning resources.) Transfusion Medicine and Hemostasis. https://doi.org/10.1016/B978-0-12-813726-0.00059-3 Copyright © 2019 Elsevier Inc. All rights reserved.
371
372
Blood Management
Timely pre-op evaluation
Minimize phlebotomy losses
-Optimize hemoglobin
-No standing orders
-Optimize coagulation
-Low volume tubes -Point-of-care testing
-Pre-operative donation -Pre-operative plateletrich plasmapheresis -Acute normovolemic hemodilution -Intra- and post-operative cell salvage
FIGURE 59.2 Patient blood management (PBM) matrix: key tenets of PBM.
Minimize peri-operative blood loss
Implement evidencebased guidelines
-Drugs: DDAVP, antifibrinolytics, topical hemostatics
-Transfusion thresholds
-Operative technique
-Audit metrics
-Good post-operative management
-Transfusion indications -Multidisciplinary involvement
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
-Treat anemia
-Use previously drawn specimens if possible
Autologous blood conservation
Patient Blood Management
373
measurable improvements. An integral component is engagement and education of ordering providers. Thus, successful PBM require active input, commitment, and leadership from medical, surgical, anesthesia, intensive care, and hospitalist services, with operational support from administration, finance, and information technology. Paramount to the success of the program is an initial audit of current transfusion practice, ideally organized by medical specialty and even by individual physicians within that specialty. Appropriate use of products should be audited, including modified (irradiated or washed) and autologous products. Evidence-based transfusion guidelines must then be developed by a multidisciplinary team, usually through transfusion committee. Creation of specific guidelines for certain populations, scenarios, or diseases, such as pediatric, massive transfusion, or sickle cell, is also typically developed. Transfusion guidelines are ideally incorporated into the ordering process, and physicians and other hospital staff must be educated to them to ensure understanding and compliance. Appropriate audit metrics to determine whether guidelines are being followed must be developed, and data collected, analyzed, and acted on. Auditing can be performed prospectively, concurrently, or retrospectively, and institutional information systems should be harnessed for automated data collection and analytic ease. Possible audit metrics include blood use per diagnosis-related group, pretransfusion hemoglobin and INR levels, blood product use and blood recovery use for specific surgical procedures, and clinically relevant outcomes. Feedback through repeat audits that normalize for severity of illness, compare physicians with their peers, include patient outcomes, and use of transfusion alternatives should be presented at all levels of the hospital hierarchy to stimulate staff awareness and motivation for improvement.
Minimizing Inappropriate Blood Use Through Evidence-Based Guidelines: Ideally, physiologic indicators of tissue oxygen delivery and ischemia should guide RBC transfusion therapy. Randomized controlled studies in critical care populations, both adult and pediatric, show no difference in functional outcome, morbidity, or survival between restrictive (transfusing for hemoglobin <7 g/dL) and liberal (transfusing for hemoglobin <10 g/dL) transfusion strategies. Creating restrictive transfusion criteria reduces the likelihood of transfusion with an average savings of a single RBC unit per transfused patient, without harming the patient. In other hospitalized patients, the RBC transfusion threshold should be individually assessed for each patient depending on their comorbidities and anemia tolerance. A recent trial in hip fracture repair patients >50 years old and with cardiovascular disease showed no difference in survival or functional outcome between liberal and restrictive (hemoglobin <8 g/dL) transfusion strategy. Prophylactic platelet transfusion in the absence of bleeding, fever, or sepsis, or an interventional procedure is not indicated with platelet count >10,000/μL. Although not based on randomized controlled trials, many centers transfuse to platelet count of 50,000/μL for interventional procedures, but recent data suggest that, at least for relatively minor-risk surgeries such as central venous catheter placement, platelet count of >20,000/μL is sufficient. Institutions typically use platelet threshold of 20,000/μL in the presence of fever, sepsis, or other bleeding risks and threshold of 50,000/μL in the presence of active bleeding. In regard to plasma transfusion, a recent metaanalysis of randomized controlled trials showed no definite benefit to plasma transfusion in reducing blood loss in either
374
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
prophylactic or therapeutic setting. Typically, corrections in international normalized ratio (INR) are small unless pretransfusion INR is >2.5 in the setting of bleeding.
Minimizing Phlebotomy-Related Blood Loss: Phlebotomy-related losses can significantly contribute to anemia and transfusion requirements in hospitalized patients, especially in the intensive care unit setting. Both frequency and volume of blood draws should be limited. Strategies to limit blood draw frequency include the following: limiting orders to only medically necessary tests, embedding disease-specific clinical guidelines into order forms or computer screens, and eliminating “standing” orders. Strategies to limit volume collected include the following: use of low-volume tubes, reducing discard volume from indwelling lines, and point-of-care testing. Pointof-care testing requires smaller blood volumes and has quicker turnaround time than standard laboratory testing. Point-of-care instrumentation is available for blood counts, standard coagulation parameters, and thromboelastography/rotational thromboelastometry measurements.
Treating Preoperative Anemia and Coagulopathy: Preoperative anemia is the strongest predictor of perioperative transfusion and increases risk of perioperative complications. Often presurgical laboratory testing is performed or reviewed too late to treat anemia (iron, B12, folate, or erythropoietin). Erythropoietin can also be used preoperatively to facilitate preoperative autologous donation (PAD) or acute normovolemic hemodilution (ANH). Concomitant intravenous iron supplementation can be used as feasible. Ideally, there is a multidisciplinary preoperative anemia clinic to prepare these patients. Evaluation includes medical history, including personal and family history of bleeding and use of anticoagulant or antiplatelet medications. Patients should be provided a schedule for switching long-acting anticoagulant or antiplatelet drugs to shorter acting agents, to be stopped immediately before surgery. Herbal or vitamin supplements may also affect bleeding risk and should be discontinued 1–2 weeks preoperatively.
Autologous Blood Conservation: Autologous blood transfusion minimizes, including PAD, ANH, and perioperative blood recovery, allogeneic blood risks such as transfusion-transmitted disease.
Preoperative Autologous Donation: PAD was used frequently in elective procedures with high likelihood of significant blood loss, but its role has been substantially decreased due to improved surgical techniques and its costs and risks. These costs and risks include wastage of ∼50% of autologous blood collected (unused); administrative costs from extra handling of such units; risk of inducing preoperative anemia, which increases the likelihood of transfusion of both autologous and allogeneic RBCs; and risk of clerical errors with transfusion of incorrect product. Additionally, the number of PAD units that can be collected and transfused is limited by 42-day RBC shelf life. RBC units can be frozen for up to 10 years to allow more collections: thawing and deglycerolizing takes a few hours, and thawed products only have a 24-hour shelf life. Furthermore, delays in sending the blood expeditiously to the requesting hospital and then thawing and deglycerolizing are often encountered.
Patient Blood Management
375
PAD is most useful in individuals with anticipated elective surgery who have high-frequency or multiple RBC alloantibodies, or IgA deficiency (particularly with plasma or platelet products). Long-term frozen storage without anticipated surgery, however, is of dubious value; significant autologous blood would have to be collected to meet emergency needs. With the advent of molecular testing, blood centers have increased ability to identify rare units, thus decreasing the use and need for autologous frozen blood. PAD results in decreased hemoglobin, which takes time to recover. Adequate iron stores must be ensured through oral or intravenous iron replacement therapy as needed. Intravenous compared with oral iron acts faster and more effectively, and newer formulations have little risk of anaphylaxis. Erythropoietin can also be used to increase number/frequency of PAD products collected, up to one RBC unit per week of treatment. PAD can be well tolerated by high-risk donors, such as the elderly, children, pregnant women, and patients with atherosclerotic coronary artery disease.
Acute Normovolemic Hemodilution: ANH involves removal of one or more whole blood units into standard collection bags containing citrate anticoagulation and replacement of lost volume with crystalloids or colloids. ANH reduces RBC loss because blood shed subsequently has lower hematocrit: for example, 2-L blood loss at hematocrit of 20% results in 400 mL rather than 900 mL RBC loss at hematocrit of 45%. Cardiovascular status should be closely monitored during hemodilution procedure. The degree of anemia can affect oxygen transport, although concomitant drop in blood viscosity and compensatory increased cardiac output tend to offset this risk. Collected blood is stored and reinfused in the operating room during surgery, in reverse order of collection to transfuse bags with highest hematocrit toward end of surgery, after blood loss is controlled. When stored at room temperature (up to 8 hours), it will contain functional platelets and clotting factors. Recent metaanalyses suggest that ANH reduces allogeneic blood transfusion, particularly in cardiac surgery, but studies are complicated by significant heterogeneity and publication bias.
Intraoperative Blood Recovery: This is when blood shed into operative field is recovered, mixed with anticoagulant, and stored in a sterile reservoir until enough blood is collected for reinfusion. Approximately, 50% of blood lost during surgical procedure can be recovered. Intraoperative blood recovery should be considered for surgeries where mean transfusion rate is at least 1 unit. Devices are available that collect blood for reinfusion, either with or without washing before transfusion. Devices that wash blood (by centrifugation with normal saline) are preferable, to remove free hemoglobin, activated clotting and complement factors, inflammatory cytokines, fat particles, and contaminants. Large volumes can be processed quickly in the event of rapid blood loss. The processed product contains RBCs diluted in saline to a >45% hematocrit and can be stored at room temperature up to 8 hours from completion of processing. Unwashed products usually have hematocrit of 20%–30% (due to dilution with irrigation fluids), must be filtered to remove clots and tissue debris, and can be stored at room temperature up to 8 hours from start of collection, due to risk from other contaminants.
376
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
Postoperative Blood Recovery: This is when blood shed from surgical drains and/or wounds is recovered and reinfused. This is predominantly used in cardiac and orthopedic surgery, where reduction in allogeneic blood use has been demonstrated; drainage sites include mediastinum or knee/hip sites. Blood salvaged from a serosal cavity has little residual fibrinogen or platelets to allow clotting; therefore, anticoagulant addition is usually unnecessary. Product can be washed or not. Unwashed blood may contain undesirable constituents as previously described but is usually well tolerated.
Adverse Events: Blood recovery from a contaminated site, such as with spilled intestinal contents, is relatively contraindicated, but bacterial contamination may still occur with environmental or skin organisms such as coagulase-positive and coagulase- negative Staphylococcus, Propionibacterium, and Corynebacterium species. Tumor cell contamination of recovered blood is a theoretical concern with malignancies, but increased risk of recurrence or metastasis with reinfusion is unproven and use of leukoreduction filters removes most tumor cells. Aspiration of pharmacologic or hemostatic agents, fat, heavily bacterially contaminated fluids, amniotic fluid, gastric fluid, or bone fragments should be avoided through use of a double suction setup. Care must be taken to vent air from the final product bag for infusion, to prevent potentially fatal air embolism. Adverse effects including respiratory distress, hypotension with anaphylaxis, and fever are more likely when product is collected over long-time interval (maximum of 6 hours from start of postoperative collection allowed).
Minimizing Perioperative Blood Loss: Perioperative blood loss can be minimized by the following: (1) drugs to reduce surgical bleeding, (2) operative techniques to reduce surgical bleeding, and (3) adequate postoperative management (Table 59.1).
Drugs Antifibrinolytics: Tranexamic acid (TXA) and α-aminocaproic acid, lysine analog inhibitors of plasminogen activation and plasmin activity, are the primary antifibrinolytics used in the United States, with TXA more commonly studied. TXA has been shown to reduce death from bleeding in trauma and postpartum hemorrhage. TXA also reduces blood loss and allogeneic RBC transfusion in orthopedic and on-pump cardiac surgery in adults, with no evidence of increased thromboembolic or mortality risk. TXA in off-pump cardiac surgery, however, has been associated with a possible risk of seizures. TXA is also used topically in orthopedic surgery. Topical Hemostatic Agents: Topical hemostatic agents can be divided into three basic categories: thrombin-based fibrin sealants; autologous platelet gel; and commercial derivatives of collagen, gelatin, and cellulose that provide a matrix for endogenous coagulation. Thrombin-based agents and autologous platelet gel contain active clotting factors, while collagen, gelatin, and cellulose are nonactive agents forming physical matrix over bleeding site. These mechanical agents may be sufficient for bleeding patients with intact coagulation, whereas active hemostatic agents are appropriate for coagulopathic patients with bleeding. Fibrin sealant, combination of a solution of human thrombin and calcium with a solution of human fibrinogen and factor XII to form fibrin, appear to be safe and may reduce allogeneic transfusion and perioperative blood loss in various surgical procedures.
377
Patient Blood Management
TABLE 59.1 Potential Perioperative Patient Blood Management Strategies Preoperative Strategies to Augment Hemoglobin Levels
Intraoperative Blood Management Strategies
Postoperative Blood Management Strategies
Restrictive transfusion threshold strategies guided by appropriate evidence base
Restrictive transfusion threshold strategies guided by appropriate evidence base
Restrictive transfusion threshold guided by appropriate evidence base
Minimize phlebotomy-related blood loss preoperatively
Minimize phlebotomy-related blood loss intraoperatively
Minimize phlebotomy-related blood loss postoperatively
Treating preoperative anemia: • Oral and Intravenous iron replacement (with or without concomitant folate)
Intraoperative blood recovery and cell salvage
Postoperative blood recovery
Treating preoperative anemia: • Erythropoiesis-stimulating agents e.g., erythropoietin (with or without concomitant iron and folate)
Improved surgical techniques, e.g., robotic surgeries
Repleting vitamin K postoperatively
Autologous blood conservation (decreasing evidence base)
Acute Normovolemic hemodilution
Use of antifibrinolytic agents: TXA, EACA as appropriate, e.g., postpartum hemorrhage
Prophylactic use of fibrinogen concentrates Use of antifibrinolytic agents: tranexamic acid (TXA), epsilon aminocaproic acid (EACA) Use of point-of-care testing (e.g., Thromboelastography or Rotational Thromboelastometry to guide transfusion decisions Fresh whole blood or reconstituted whole blood
Operative Techniques: Certain operative principles apply to all surgeries. Maintenance of normal body temperature and pH is critical for normal platelet and coagulation function. Body temperature can be maintained through blood/ intravenous fluid warmers, air-warming devices, and physical coverage. Acidosis is avoided by preventing hypovolemia, hypotension, and excessive normal saline administration. Careful planning can improve pace and efficiency of surgery and thus minimize blood loss. Surgical techniques that reduce bleeding include laparoscopic, robotic, or endovascular approaches; or preoperative embolization. Surgical instruments such as ultrasonic scalpels, bipolar vessel sealers, and argon beam coagulators can improve hemostasis at incision sites. Other techniques include patient positioning to elevate blood loss site; decreasing pressure on abdominal contents (which can obstruct inferior vena cava flow); tourniquet use; reduction of central venous pressure; infusion of local vasoconstrictive agents; and controlled hypotension.
378
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
Adequate Postoperative Management: Postoperative blood salvage should be considered. Body temperature, cardiac output, and ventilation/oxygenation should continue to be monitored. Rapid diagnosis and control of surgical hemorrhage, with reexploration as needed, is crucial. Postoperative anemia should be evaluated. Patients may have absolute or functional iron deficiency, for which intravenous iron and/or erythropoietin treatment may be appropriate. Drug side effects or lack of stress gastritis prophylaxis can also contribute to anemia.
Further Reading AABB. (2015). AABB White Papers: Building a better patient blood management program identifying tools, solving problems and promoting patient safety. Carless, P. A., Henry, D. A., Moxey, A. J., O’Connell, D., Brown, T., & Fergusson, D. A. (2010). Cell salvage for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev, 4, CD001888. Carson, J. L., Guyatt, G. H., Heddle, N. M., et al. (2016). Clinical practice guidelines from the AABB: Red blood cell transfusion thresholds and storage. JAMA, 316(19), 2025–2035. Ellingson, K. D., Sapiano, M. R. P., Haass, K. A., et al. (2017). Continued decline in blood collection and transfusion in the United States-2015. Transfusion, 57(Suppl. 2), 1588–1598. Henry, D. A., Carless, P. A., Moxey, A. J., et al. (2011). Anti-fibrinolytic use for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev, 3, CD001886. Kaufman, R. M., Djulbegovic, B., Gernsheimer, T., et al. (2015). Platelet transfusion: A clinical practice guideline from the AABB. Ann Intern Med, 162(3), 205–213. Levy, J. H., & Sniecinski, R. M. (2012). Prohemostatic treatment in cardiac surgery. Semin Thromb Hemost, 38, 237–243. Liumbruno, G. M., Bennardello, F., Lattanzio, A., Piccoli, P., & Rossetti, G. (2011). Recommendations for the transfusion management of patients in the peri-operative period. I. The pre-operative period. Blood Transfus, 9, 19–40. Markowitz, M. A., Waters, J. H., & Ness, P. M. (2014). Patient blood management: A primary theme in transfusion medicine. Transfusion, 54(10 Pt 2), 2587. Yang, L., Stanworth, S., Hopewell, S., Doree, C., & Murphy, M. (2012). Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion, 52, 1673–1686.
Patient Blood Management Ruchika Goel, MD, MPH and Patricia A. Shi, MD Patient blood management (PBM) is the term given to the appropriate use of blood transfusion to optimize patient care. Patient-centric approach is its core principle (Fig. 59.1). PBM is “transfusing the right product in the right dose to the right patient at the right time for the right reason.” PBM has five main tenets (Fig. 59.2). In addition to improving patient safety, PBM programs decrease hospital costs and conserve clinical resources. Cost can range from $522–1183/RBC unit when accounting for storage, testing, and labor.
Implementing Blood Management Program: Hospital-wide, comprehensive, and multidisciplinary PBM program can optimize patient care, avoid unnecessary transfusions of blood products, and limit adverse effects. Successful PBM programs are rooted in evidence-based medicine and enhance patient safety and outcomes through
Optimization Of Red Cell Mass Pre-op Anemia Management
Multi-disciplinary Blood Conservation Strategies
Patient Centered Approach of all PBM Tenets
Optimizing Coagulation and Improved Hemostasis
Patient Centered And Evidence Based Clinical Decision Making
FIGURE 59.1 Key principles of patient blood management. (Adapted from Society of Blood Management 2012 learning resources.) Transfusion Medicine and Hemostasis. https://doi.org/10.1016/B978-0-12-813726-0.00059-3 Copyright © 2019 Elsevier Inc. All rights reserved.
371
372
Blood Management
Timely pre-op evaluation
Minimize phlebotomy losses
-Optimize hemoglobin
-No standing orders
-Optimize coagulation
-Low volume tubes -Point-of-care testing
-Pre-operative donation -Pre-operative plateletrich plasmapheresis -Acute normovolemic hemodilution -Intra- and post-operative cell salvage
FIGURE 59.2 Patient blood management (PBM) matrix: key tenets of PBM.
Minimize peri-operative blood loss
Implement evidencebased guidelines
-Drugs: DDAVP, antifibrinolytics, topical hemostatics
-Transfusion thresholds
-Operative technique
-Audit metrics
-Good post-operative management
-Transfusion indications -Multidisciplinary involvement
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
-Treat anemia
-Use previously drawn specimens if possible
Autologous blood conservation
Patient Blood Management
373
measurable improvements. An integral component is engagement and education of ordering providers. Thus, successful PBM require active input, commitment, and leadership from medical, surgical, anesthesia, intensive care, and hospitalist services, with operational support from administration, finance, and information technology. Paramount to the success of the program is an initial audit of current transfusion practice, ideally organized by medical specialty and even by individual physicians within that specialty. Appropriate use of products should be audited, including modified (irradiated or washed) and autologous products. Evidence-based transfusion guidelines must then be developed by a multidisciplinary team, usually through transfusion committee. Creation of specific guidelines for certain populations, scenarios, or diseases, such as pediatric, massive transfusion, or sickle cell, is also typically developed. Transfusion guidelines are ideally incorporated into the ordering process, and physicians and other hospital staff must be educated to them to ensure understanding and compliance. Appropriate audit metrics to determine whether guidelines are being followed must be developed, and data collected, analyzed, and acted on. Auditing can be performed prospectively, concurrently, or retrospectively, and institutional information systems should be harnessed for automated data collection and analytic ease. Possible audit metrics include blood use per diagnosis-related group, pretransfusion hemoglobin and INR levels, blood product use and blood recovery use for specific surgical procedures, and clinically relevant outcomes. Feedback through repeat audits that normalize for severity of illness, compare physicians with their peers, include patient outcomes, and use of transfusion alternatives should be presented at all levels of the hospital hierarchy to stimulate staff awareness and motivation for improvement.
Minimizing Inappropriate Blood Use Through Evidence-Based Guidelines: Ideally, physiologic indicators of tissue oxygen delivery and ischemia should guide RBC transfusion therapy. Randomized controlled studies in critical care populations, both adult and pediatric, show no difference in functional outcome, morbidity, or survival between restrictive (transfusing for hemoglobin <7 g/dL) and liberal (transfusing for hemoglobin <10 g/dL) transfusion strategies. Creating restrictive transfusion criteria reduces the likelihood of transfusion with an average savings of a single RBC unit per transfused patient, without harming the patient. In other hospitalized patients, the RBC transfusion threshold should be individually assessed for each patient depending on their comorbidities and anemia tolerance. A recent trial in hip fracture repair patients >50 years old and with cardiovascular disease showed no difference in survival or functional outcome between liberal and restrictive (hemoglobin <8 g/dL) transfusion strategy. Prophylactic platelet transfusion in the absence of bleeding, fever, or sepsis, or an interventional procedure is not indicated with platelet count >10,000/μL. Although not based on randomized controlled trials, many centers transfuse to platelet count of 50,000/μL for interventional procedures, but recent data suggest that, at least for relatively minor-risk surgeries such as central venous catheter placement, platelet count of >20,000/μL is sufficient. Institutions typically use platelet threshold of 20,000/μL in the presence of fever, sepsis, or other bleeding risks and threshold of 50,000/μL in the presence of active bleeding. In regard to plasma transfusion, a recent metaanalysis of randomized controlled trials showed no definite benefit to plasma transfusion in reducing blood loss in either
374
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
prophylactic or therapeutic setting. Typically, corrections in international normalized ratio (INR) are small unless pretransfusion INR is >2.5 in the setting of bleeding.
Minimizing Phlebotomy-Related Blood Loss: Phlebotomy-related losses can significantly contribute to anemia and transfusion requirements in hospitalized patients, especially in the intensive care unit setting. Both frequency and volume of blood draws should be limited. Strategies to limit blood draw frequency include the following: limiting orders to only medically necessary tests, embedding disease-specific clinical guidelines into order forms or computer screens, and eliminating “standing” orders. Strategies to limit volume collected include the following: use of low-volume tubes, reducing discard volume from indwelling lines, and point-of-care testing. Pointof-care testing requires smaller blood volumes and has quicker turnaround time than standard laboratory testing. Point-of-care instrumentation is available for blood counts, standard coagulation parameters, and thromboelastography/rotational thromboelastometry measurements.
Treating Preoperative Anemia and Coagulopathy: Preoperative anemia is the strongest predictor of perioperative transfusion and increases risk of perioperative complications. Often presurgical laboratory testing is performed or reviewed too late to treat anemia (iron, B12, folate, or erythropoietin). Erythropoietin can also be used preoperatively to facilitate preoperative autologous donation (PAD) or acute normovolemic hemodilution (ANH). Concomitant intravenous iron supplementation can be used as feasible. Ideally, there is a multidisciplinary preoperative anemia clinic to prepare these patients. Evaluation includes medical history, including personal and family history of bleeding and use of anticoagulant or antiplatelet medications. Patients should be provided a schedule for switching long-acting anticoagulant or antiplatelet drugs to shorter acting agents, to be stopped immediately before surgery. Herbal or vitamin supplements may also affect bleeding risk and should be discontinued 1–2 weeks preoperatively.
Autologous Blood Conservation: Autologous blood transfusion minimizes, including PAD, ANH, and perioperative blood recovery, allogeneic blood risks such as transfusion-transmitted disease.
Preoperative Autologous Donation: PAD was used frequently in elective procedures with high likelihood of significant blood loss, but its role has been substantially decreased due to improved surgical techniques and its costs and risks. These costs and risks include wastage of ∼50% of autologous blood collected (unused); administrative costs from extra handling of such units; risk of inducing preoperative anemia, which increases the likelihood of transfusion of both autologous and allogeneic RBCs; and risk of clerical errors with transfusion of incorrect product. Additionally, the number of PAD units that can be collected and transfused is limited by 42-day RBC shelf life. RBC units can be frozen for up to 10 years to allow more collections: thawing and deglycerolizing takes a few hours, and thawed products only have a 24-hour shelf life. Furthermore, delays in sending the blood expeditiously to the requesting hospital and then thawing and deglycerolizing are often encountered.
Patient Blood Management
375
PAD is most useful in individuals with anticipated elective surgery who have high-frequency or multiple RBC alloantibodies, or IgA deficiency (particularly with plasma or platelet products). Long-term frozen storage without anticipated surgery, however, is of dubious value; significant autologous blood would have to be collected to meet emergency needs. With the advent of molecular testing, blood centers have increased ability to identify rare units, thus decreasing the use and need for autologous frozen blood. PAD results in decreased hemoglobin, which takes time to recover. Adequate iron stores must be ensured through oral or intravenous iron replacement therapy as needed. Intravenous compared with oral iron acts faster and more effectively, and newer formulations have little risk of anaphylaxis. Erythropoietin can also be used to increase number/frequency of PAD products collected, up to one RBC unit per week of treatment. PAD can be well tolerated by high-risk donors, such as the elderly, children, pregnant women, and patients with atherosclerotic coronary artery disease.
Acute Normovolemic Hemodilution: ANH involves removal of one or more whole blood units into standard collection bags containing citrate anticoagulation and replacement of lost volume with crystalloids or colloids. ANH reduces RBC loss because blood shed subsequently has lower hematocrit: for example, 2-L blood loss at hematocrit of 20% results in 400 mL rather than 900 mL RBC loss at hematocrit of 45%. Cardiovascular status should be closely monitored during hemodilution procedure. The degree of anemia can affect oxygen transport, although concomitant drop in blood viscosity and compensatory increased cardiac output tend to offset this risk. Collected blood is stored and reinfused in the operating room during surgery, in reverse order of collection to transfuse bags with highest hematocrit toward end of surgery, after blood loss is controlled. When stored at room temperature (up to 8 hours), it will contain functional platelets and clotting factors. Recent metaanalyses suggest that ANH reduces allogeneic blood transfusion, particularly in cardiac surgery, but studies are complicated by significant heterogeneity and publication bias.
Intraoperative Blood Recovery: This is when blood shed into operative field is recovered, mixed with anticoagulant, and stored in a sterile reservoir until enough blood is collected for reinfusion. Approximately, 50% of blood lost during surgical procedure can be recovered. Intraoperative blood recovery should be considered for surgeries where mean transfusion rate is at least 1 unit. Devices are available that collect blood for reinfusion, either with or without washing before transfusion. Devices that wash blood (by centrifugation with normal saline) are preferable, to remove free hemoglobin, activated clotting and complement factors, inflammatory cytokines, fat particles, and contaminants. Large volumes can be processed quickly in the event of rapid blood loss. The processed product contains RBCs diluted in saline to a >45% hematocrit and can be stored at room temperature up to 8 hours from completion of processing. Unwashed products usually have hematocrit of 20%–30% (due to dilution with irrigation fluids), must be filtered to remove clots and tissue debris, and can be stored at room temperature up to 8 hours from start of collection, due to risk from other contaminants.
376
Ruchika Goel, MD, MPH and Patricia A. Shi, MD
Postoperative Blood Recovery: This is when blood shed from surgical drains and/or wounds is recovered and reinfused. This is predominantly used in cardiac and orthopedic surgery, where reduction in allogeneic blood use has been demonstrated; drainage sites include mediastinum or knee/hip sites. Blood salvaged from a serosal cavity has little residual fibrinogen or platelets to allow clotting; therefore, anticoagulant addition is usually unnecessary. Product can be washed or not. Unwashed blood may contain undesirable constituents as previously described but is usually well tolerated.
Adverse Events: Blood recovery from a contaminated site, such as with spilled intestinal contents, is relatively contraindicated, but bacterial contamination may still occur with environmental or skin organisms such as coagulase-positive and coagulase- negative Staphylococcus, Propionibacterium, and Corynebacterium species. Tumor cell contamination of recovered blood is a theoretical concern with malignancies, but increased risk of recurrence or metastasis with reinfusion is unproven and use of leukoreduction filters removes most tumor cells. Aspiration of pharmacologic or hemostatic agents, fat, heavily bacterially contaminated fluids, amniotic fluid, gastric fluid, or bone fragments should be avoided through use of a double suction setup. Care must be taken to vent air from the final product bag for infusion, to prevent potentially fatal air embolism. Adverse effects including respiratory distress, hypotension with anaphylaxis, and fever are more likely when product is collected over long-time interval (maximum of 6 hours from start of postoperative collection allowed).
Minimizing Perioperative Blood Loss: Perioperative blood loss can be minimized by the following: (1) drugs to reduce surgical bleeding, (2) operative techniques to reduce surgical bleeding, and (3) adequate postoperative management (Table 59.1).
Drugs Antifibrinolytics: Tranexamic acid (TXA) and α-aminocaproic acid, lysine analog inhibitors of plasminogen activation and plasmin activity, are the primary antifibrinolytics used in the United States, with TXA more commonly studied. TXA has been shown to reduce death from bleeding in trauma and postpartum hemorrhage. TXA also reduces blood loss and allogeneic RBC transfusion in orthopedic and on-pump cardiac surgery in adults, with no evidence of increased thromboembolic or mortality risk. TXA in off-pump cardiac surgery, however, has been associated with a possible risk of seizures. TXA is also used topically in orthopedic surgery. Topical Hemostatic Agents: Topical hemostatic agents can be divided into three basic categories: thrombin-based fibrin sealants; autologous platelet gel; and commercial derivatives of collagen, gelatin, and cellulose that provide a matrix for endogenous coagulation. Thrombin-based agents and autologous platelet gel contain active clotting factors, while collagen, gelatin, and cellulose are nonactive agents forming physical matrix over bleeding site. These mechanical agents may be sufficient for bleeding patients with intact coagulation, whereas active hemostatic agents are appropriate for coagulopathic patients with bleeding. Fibrin sealant, combination of a solution of human thrombin and calcium with a solution of human fibrinogen and factor XII to form fibrin, appear to be safe and may reduce allogeneic transfusion and perioperative blood loss in various surgical procedures.
377
Patient Blood Management
TABLE 59.1 Potential Perioperative Patient Blood Management Strategies Preoperative Strategies to Augment Hemoglobin Levels
Intraoperative Blood Management Strategies
Postoperative Blood Management Strategies
Restrictive transfusion threshold strategies guided by appropriate evidence base
Restrictive transfusion threshold strategies guided by appropriate evidence base
Restrictive transfusion threshold guided by appropriate evidence base
Minimize phlebotomy-related blood loss preoperatively
Minimize phlebotomy-related blood loss intraoperatively
Minimize phlebotomy-related blood loss postoperatively
Treating preoperative anemia: • Oral and Intravenous iron replacement (with or without concomitant folate)
Intraoperative blood recovery and cell salvage
Postoperative blood recovery
Treating preoperative anemia: • Erythropoiesis-stimulating agents e.g., erythropoietin (with or without concomitant iron and folate)
Improved surgical techniques, e.g., robotic surgeries
Repleting vitamin K postoperatively
Autologous blood conservation (decreasing evidence base)
Acute Normovolemic hemodilution
Use of antifibrinolytic agents: TXA, EACA as appropriate, e.g., postpartum hemorrhage
Prophylactic use of fibrinogen concentrates Use of antifibrinolytic agents: tranexamic acid (TXA), epsilon aminocaproic acid (EACA) Use of point-of-care testing (e.g., Thromboelastography or Rotational Thromboelastometry to guide transfusion decisions Fresh whole blood or reconstituted whole blood
Operative Techniques: Certain operative principles apply to all surgeries. Maintenance of normal body temperature and pH is critical for normal platelet and coagulation function. Body temperature can be maintained through blood/ intravenous fluid warmers, air-warming devices, and physical coverage. Acidosis is avoided by preventing hypovolemia, hypotension, and excessive normal saline administration. Careful planning can improve pace and efficiency of surgery and thus minimize blood loss. Surgical techniques that reduce bleeding include laparoscopic, robotic, or endovascular approaches; or preoperative embolization. Surgical instruments such as ultrasonic scalpels, bipolar vessel sealers, and argon beam coagulators can improve hemostasis at incision sites. Other techniques include patient positioning to elevate blood loss site; decreasing pressure on abdominal contents (which can obstruct inferior vena cava flow); tourniquet use; reduction of central venous pressure; infusion of local vasoconstrictive agents; and controlled hypotension.
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Adequate Postoperative Management: Postoperative blood salvage should be considered. Body temperature, cardiac output, and ventilation/oxygenation should continue to be monitored. Rapid diagnosis and control of surgical hemorrhage, with reexploration as needed, is crucial. Postoperative anemia should be evaluated. Patients may have absolute or functional iron deficiency, for which intravenous iron and/or erythropoietin treatment may be appropriate. Drug side effects or lack of stress gastritis prophylaxis can also contribute to anemia.
Further Reading AABB. (2015). AABB White Papers: Building a better patient blood management program identifying tools, solving problems and promoting patient safety. Carless, P. A., Henry, D. A., Moxey, A. J., O’Connell, D., Brown, T., & Fergusson, D. A. (2010). Cell salvage for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev, 4, CD001888. Carson, J. L., Guyatt, G. H., Heddle, N. M., et al. (2016). Clinical practice guidelines from the AABB: Red blood cell transfusion thresholds and storage. JAMA, 316(19), 2025–2035. Ellingson, K. D., Sapiano, M. R. P., Haass, K. A., et al. (2017). Continued decline in blood collection and transfusion in the United States-2015. Transfusion, 57(Suppl. 2), 1588–1598. Henry, D. A., Carless, P. A., Moxey, A. J., et al. (2011). Anti-fibrinolytic use for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev, 3, CD001886. Kaufman, R. M., Djulbegovic, B., Gernsheimer, T., et al. (2015). Platelet transfusion: A clinical practice guideline from the AABB. Ann Intern Med, 162(3), 205–213. Levy, J. H., & Sniecinski, R. M. (2012). Prohemostatic treatment in cardiac surgery. Semin Thromb Hemost, 38, 237–243. Liumbruno, G. M., Bennardello, F., Lattanzio, A., Piccoli, P., & Rossetti, G. (2011). Recommendations for the transfusion management of patients in the peri-operative period. I. The pre-operative period. Blood Transfus, 9, 19–40. Markowitz, M. A., Waters, J. H., & Ness, P. M. (2014). Patient blood management: A primary theme in transfusion medicine. Transfusion, 54(10 Pt 2), 2587. Yang, L., Stanworth, S., Hopewell, S., Doree, C., & Murphy, M. (2012). Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion, 52, 1673–1686.