key: cord-0805483-43geausg authors: Shander, Aryeh; Goobie, Susan M.; Warner, Matthew A.; Aapro, Matti; Bisbe, Elvira; Perez-Calatayud, Angel A.; Callum, Jeannie; Cushing, Melissa M.; Dyer, Wayne B.; Erhard, Jochen; Faraoni, David; Farmer, Shannon; Fedorova, Tatyana; Frank, Steven M.; Froessler, Bernd; Gombotz, Hans; Gross, Irwin; Guinn, Nicole R.; Haas, Thorsten; Hamdorf, Jeffrey; Isbister, James P.; Javidroozi, Mazyar; Ji, Hongwen; Kim, Young-Woo; Kor, Daryl J.; Kurz, Johann; Lasocki, Sigismond; Leahy, Michael F.; Lee, Cheuk-Kwong; Lee, Jeong Jae; Louw, Vernon; Meier, Jens; Mezzacasa, Anna; Munoz, Manuel; Ozawa, Sherri; Pavesi, Marco; Shander, Nina; Spahn, Donat R.; Spiess, Bruce D.; Thomson, Jackie; Trentino, Kevin; Zenger, Christoph; Hofmann, Axel title: Essential Role of Patient Blood Management in a Pandemic: A Call for Action date: 2020-04-20 journal: Anesth Analg DOI: 10.1213/ane.0000000000004844 sha: 623c96852631a001198005be38adc8054565bcb3 doc_id: 805483 cord_uid: 43geausg The World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and “flattening the curve” while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient’s own blood. This multinational and diverse group of authors issue this “Call to Action” underscoring “The Essential Role of Patient Blood Management in the Management of Pandemics” and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches. G iven the recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing worldwide, widespread human-to-human transmission of the related Coronavirus Disease 2019 , the World Health Organization (WHO) has declared a pandemic status for this virus and the virus-related disease. As one of the corollaries, public health authorities and blood services are concerned with decreasing blood donations, ultimately resulting in blood shortages that will unquestionably lead to difficult and controversial transfusion rationing decisions by frontline health care providers. Considering that blood is a perishable commodity with a very short expiration time, as with past pandemics, blood services are being challenged to maintain their inventory during the current COVID-19 pandemics. On the other hand, analyses after past natural and man-made disasters have demonstrated either no change or a reduction in the demand for blood and its use. 1, 2 BLOOD SUPPLY CHALLENGES DURING PANDEMICS The influenza A virus subtype H1N1 (H1N1) pandemic had a significant impact on the blood supply due to donors' fear of exposure to the virus at a hospital or a free-standing donor facility. 3, 4 Similarly, the COVID-19 pandemic has already led to significantly reduced blood supplies due to the cancellation of numerous community-based and mobile blood drives, as well as a marked reduction in donors arriving for scheduled appointments. For instance, as a result of the current pandemic and restrictions on congregating through social distancing, to date in the United States, nearly 4000 American Red Cross blood drives have been canceled across the country. Hospital-based collections have been cancelled due to institutional concerns regarding donors spreading COVID-19 to hospitalized patients or vice versa. These cancellations have resulted in some 130,000 fewer blood donations in only a few weeks. More than 80% of the blood the American Red Cross collects comes from drives held at nonpermanent collection locations. According to the Chief Executive Officer of New York Blood Center, the main blood supplier for New York City, around 75% of their incoming blood supply was interrupted during the week of March 16, 2020, when schools, businesses, and religious institutions closed due to the coronavirus outbreak. 5 Moreover, the number of eligible donors in the course of a pandemic will inevitably decrease due to an increasing number of individuals being infected or in self-quarantine after exposure to infected persons or persons under investigation. In addition, blood collection facilities have put additional screening criteria in place, declining donors with the history of travel from infection "hot spots" in the preceding 14 days, at a time when a large proportion of the population had travelled for school spring breaks. Finally, older persons, who often represent the most reliable donor pool, are also apparently among the most vulnerable to the COVID-19 pandemic. The default response to reduced blood supplies and the limited capacity of health care facilities is the suspension of elective surgical procedures regardless of the lack of uniform definitions for "elective." 6 Yet, blood utilization for urgent and emergent interventions that can actually represent a greater demand on the blood supply is likely to remain unchanged. The same will likely be true for chronically transfusion-dependent patients, including those with malignancies, hematologic conditions (eg, sickle cell, thalassemia, myelodysplastic syndrome), and chemotherapy-induced anemia. In some cases, cancellation of elective surgeries may permit disease progression resulting in more complex and urgent situations, as the pandemic further progresses. Calls from blood centers for more donors do not sufficiently alleviate this problem. In the context of pandemics, the pressure on blood collection facilities and hospital transfusion medicine services and their staff is also increased as more and more staff members are required to self-isolate, self-quarantine, or become ill. In addition, the effort to continue standard blood donor recruitment will be diverted in part by the growing initiative to manufacture convalescent plasma from patients who have recovered from COVID-19. While this treatment option remains under investigation on a limited basis and is not currently a major source of demand for blood donations, the rapidly evolving nature of the pandemic might quickly change the landscape, creating a substantial new demand. It should also be noted that supply chains are often affected by travel restrictions, factory closings, and decreased manufacturing output, which may in turn affect the ability of blood services to maintain their testing and production facilities in times of increasing need. Another remote but significant issue is possible virus transmission via donated blood. At some stage of the pandemic, we expect that a considerable percentage of the population will be unknowingly infected by SARS-CoV-2, including the young blood donor population in which asymptomatic cases will be common. In the absence of nucleic acid testing (NAT) for blood donor screening for SARS-CoV-2, we cannot exclude, albeit theoretical at this time, the possible transmission via a blood transfusion, if some of the donated blood may be contaminated. 7 Thus, we are facing significant unknowns, and only future studies will elucidate the true risks of transfusion-transmitted SARS-CoV-2 if any. 8 For all of the above reasons, the medical community must adopt other solutions to continue and/or resume care of our patient population. Thus, the immediate and global implementation of patient blood management (PBM) should be mandated. 9,10 PBM is defined as an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood (www.ifpbm. org) or alternatively, as the timely application of evidence-based medical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss, in an effort to improve patient outcomes (www.sabm.org). The National Blood Authority (Australia) evidence-based PBM Guidelines are an exhaustive systematic review of the literature with an attendant rigorous methodology for developing recommendations, practice points, and expert opinion points. The 6 modules contain 52 Recommendations, 142 Practice Points, and 56 Expert Opinion Points. The PBM Toolbox (Tables 1-2) summarizes the practical concepts of PBM. [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] Numerous large observational studies, 66-68 several randomized controlled trials, 24,69-71 and meta-analyses 25, 72 have demonstrated significantly improved patient outcomes with PBM, while substantially reducing blood utilization. The concept of PBM proactively focuses on patient needs as well as the conditions that usually lead to transfusions, namely, blood loss, coagulopathies, platelet dysfunction, and anemia. PBM shifts the focus from reactive transfusion of patients with allogeneic blood components to preventive measures by optimally managing the patient's own blood. The PBM concept was endorsed in 2010 by the World Health Assembly through resolution WHA63.12. In 2017, it was recommended as standard of care by the European Commission. In the recent WHO Action Framework to advance universal access to safe, effective, and quality-assured blood components in 2020-2023, the effective implementation of PBM is listed as 1 of 6 goals. 73 Despite these strong recommendations and the available evidence demonstrating that the PBM model is not just an option but rather a necessity, practice change still lags very far behind. Furthermore, while expert consensus demonstrates that the PBM model improves clinical outcomes, increases patient safety, and reduces costs, hospitals with organized PBM programs are few and far between. • Change culture across your institution [11] [12] [13] • Disseminate evidence-based PBM guidelines/recommendations and detect and discourage nonevidence practices [14] [15] [16] [17] [18] [19] [20] [21] [22] • Translate evidence-based guidelines/recommendations into clinical practice 13 • Pre-and postoperative cell recovery (cell saver) 28 • ANH 29 4. Pharmaceuticals • Oral/intravenous iron [30] [31] [32] [33] • Folic acid 34 • Vitamin B 12 34, 35 • Erythropoiesis-stimulating agents 30, 32, 33 • Antifibrinolytics (tranexamic acid, aminocaproic acid) 36 assessment of March 12, 2020, on COVID-19 states that the "Implementation of Patient Blood Management (PBM) … is strongly advisable." Furthermore, the interim guidance on March 20, 2020, from the WHO on maintaining a safe and adequate blood supply during the COVID-19 pandemic recommends "Good patient blood management" to safeguard blood stocks. 74 In the current pandemic setting, both the severe limitation of available health care resources and the growing shortage of donor blood clearly support that the rapid implementation of PBM is the optimal way forward. Beyond beneficial effects on blood utilization, PBMassociated improvements in clinical outcomes, specifically, a reduction in hospital-acquired infections and reduced lengths of stay, may further decrease the burden on an overwhelmed health care system. Therefore, health care leaders and clinicians are urged and called on to immediately champion change and improve their institutional infrastructure and processes to ensure the following: Identify, Evaluate, and Treat Iron Deficiency and Anemia in Both Medical and Surgical Patients With Appropriate Pharmacological Agents In 2015, a total of 2.36 billion people or 32% of the world population were affected by anemia, representing the most prevalent of all impairments globally. 61, 75, 76 In >60% of all cases, iron deficiency was the cause of anemia. 77 However, the prevalence of anemia in hospitalized patients is significantly higher than in the general population and can reach up to 75% in specific surgical populations. 78 Anemia is associated with increased blood utilization, worse patient outcomes, and increased morbidity and mortality in surgical and medical patients of all ages. 79, 80 Prevention, early diagnosis, and prompt treatment directed by the etiology of anemia can decrease blood utilization and improve patient outcomes. Iron deficiency, with and without anemia, is common and is associated with increased mortality in cardiac surgery 81 and may be treated with oral or intravenous iron supplementation. Oral therapy is often poorly tolerated, has a slower onset of action than intravenous iron, and is insufficient to correct iron deficiency in the presence of ongoing bleeding. Intravenous iron therapy is preferred for those with intolerance to oral therapy, severe anemia (ie, hemoglobin < 10 g/dL), or planned surgical procedures or obstetrical delivery within 6 weeks. There are many formulations that allow for rapid, safe, and complete correction of iron deficiency. Women and adolescent girls presenting for obstetrical care or with 13 • Install necessary medical devices and equipment 13, 23 • Reengineer clinical pathways and infrastructure to allow appropriate preoperative/preintervention patient assessment and optimization 13,23 • Ensure appropriate waiting zones and treatment areas particularly for preoperative/preintervention patient optimization 13 • Form a multidisciplinary PBM committee 13 Abbreviations: ABC, Anemia, Blood loss and Coagulopathy; ANH, Acute normovolemic hemodilution; COX2, cyclooxygenase-2; DOACs, direct oral anticoagulants; 82, 83 Anemia related to other nutritional deficiencies, such as folate and vitamin B 12 , may, in many cases, be corrected with oral therapy, with both folate and vitamin B 12 typically dosed at 1 mg daily. Erythropoiesis-stimulating agents (ESAs) are exogenous forms of erythropoietin, including epoetin alfa, the longer-acting darbepoetin alfa, and other emerging ESAs, which may be used to stimulate erythropoiesis. While ESAs are often used in the long-term management of anemia in patients with chronic kidney disease and chemotherapy-induced bone marrow suppression, there has been increasing expansion to short-term use in those with preoperative anemia, particularly when anemia is deemed secondary to anemia of inflammation. 30 In preoperative patients and in the critically ill, ESA utilization with either 100,000 units weekly in the intensive care unit (ICU) or 600/kg in the preoperative period results in higher hemoglobin concentrations and reduced transfusion utilization. 71 Identify and Rapidly Address Coagulation/ Hemostatic Issues Perioperatively Coagulopathy, when not promptly recognized and corrected, can perpetuate a cycle of bleeding, blood utilization, and patient morbidity. 21 There are several evidence-based strategies available for appropriate management of coagulopathy. Point-of-care viscoelastic testing, including thromboelastography and rotational thromboelastometry, facilitates near real-time identification of coagulation abnormalities, thereby allowing rapid and targeted correction of the impaired pathway, rather than relying on unguided administration of plasma and platelets. 84, 85 Transfusion therapies can often be avoided altogether by the utilization of clotting factors such as prothrombin complex concentrates or fibrinogen concentrate. In addition to transfusion-sparing effects, clotting factors also decrease the risk of transfusion-related complications, such as transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), the leading causes of transfusionrelated morbidity and mortality. 86 Antifibrinolytic agents, including tranexamic acid and epsilon aminocaproic acid, are widely available, inexpensive, highly effective, and safe pharmacological agents that may be used to stabilize clot formation and prevent hyperfibrinolysis. The use of these agents has consistently been associated with bleeding reduction, transfusion reduction, and improved outcomes across numerous surgical procedures and in trauma settings. 36, 87 Use All Effective Blood Conservation Methods in Both Medical and Surgical Patients There are numerous modalities available for perioperative blood conservation. 88 These include avoiding hemodilution, restrictive transfusion strategies for all types of allogeneic blood components, [48] [49] [50] [51] 89 optimizing physiological response to anemia, early treatment of coagulopathy, and the use of topical hemostatic agents. Cell salvage, which involves the collection of a patient's own blood loss, filtering and washing to ensure the removal of impurities, and direct return of the autologous component to the patient, is associated with reductions in allogeneic blood component utilization. Therefore, it is recommended for all procedures with moderate-to-large volume blood loss. 28, 90 Acute normovolemic hemodilution (ANH) is a process by which a controlled volume of a patient's own blood is removed before the surgical insult followed by replacement with crystalloids or colloids. 91 In adults, this results in less red blood cell loss during the surgical procedure and allows for the reinfusion of autologous blood, rich in red blood cells, platelets, and clotting factors, when it is needed intraoperatively or postoperatively. 92 ANH provides autologous fresh whole blood or can be sequestered to deliver red blood cells, plasma, or platelets as needed, but its use is more likely to be beneficial in procedures with significant blood loss. ANH should thus be considered on a case-by-case basis. For both medical and surgical patients, it is also essential to limit iatrogenic blood loss. Most often this occurs through diagnostic phlebotomy. Methods to reduce iatrogenic blood loss include the minimization of unnecessary blood sampling, the use of pediatric small vacuum blood draws, which allow for testing on hospital automated chemistry lines, and the employment of closed-loop sampling devices. 30 Carefully Monitor Patients' Condition After Surgery and Rapidly Intervene by Either Interventional Radiology or Endoscopy for Unexpected Bleeding Depending on the Source Bleeding postoperatively and postobstetrical delivery are common and are associated with increased resource utilization and worse clinical outcomes. Therefore, it is essential that all patients receive serial evaluation for bleeding, including assessments of drain output, frequent monitoring for hemodynamic status, and physical examination. In patients with suspected bleeding or coagulopathy, point-of-care viscoelastic testing and hemoglobin assessments may be used for the rapid identification of bleeding and coagulation abnormalities, as well as the rapid employment of surgical and interventional radiology intervention to immediately achieve source control. Thoroughly Inform and Educate Medical Professionals, Patients, and Their Caregivers on the Importance of PBM; Involve Patients in Treatment and Management Decisions and Obtain Formal Consent It is important to involve these key stakeholders in the decision-making process and letting them know that their well-being and the health of their loved ones are at the center of this comprehensive effort. Patients who are chronically transfused need prompt and frequent messaging to reassure them that all efforts are being deployed to maintain their access to transfusion. Difficult decisions will need to be made for patients requiring massive transfusion for traumatic injury, gastrointestinal bleeding, and cardiovascular surgery-all with a very poor chance of shortand long-term survival. Transfusing multiple units of blood components to a single patient is not only associated with high morbidity and mortality, but such massive transfusions could also compromise the transfusion support for many other patients in need. 93 Faced with the substantial challenges during the COVID-19 pandemic that has left no one worldwide safe or unaffected, medical contributions-large or small-are urgently needed to provide the optimal and most compassionate care while using every modality to conserve resources. Appropriate resource conservation will allow for better allocation to those patients in absolute need. The authors of this "Call for Action" document represent diverse backgrounds and specialties, yet they come together with a cohesive message, underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all to implement the practical and commonsense principles of PBM and its multi- Blood and disaster-supply and demand Blood transfusion service in disasters New flu victim: blood supply. The Wall Street Journal Maintaining a safe and adequate blood supply during pandemic influenza: guidelines for blood transfusion services New York Blood Center expands capacity at donors centers; urges healthy donors to schedule appointments to maintain blood supply at this critical time Morrison launches COVID-19 Coordination Commission, cancels non-urgent surgery. 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