Anemia and Bloodless Medicine

Abstract

The use of allogenic blood transfusions has been used in the care of anemic patients with certain success. However, the use of transfusions has been associated with long term complications including blood-borne infections, allergic reactions, fever, kidney and lung disease. An increasing patient population who refuse blood transfusions as well as a national shortage of blood have given way to alternative treatments that focus on blood conservation reduce morbidity and mortality. Anemia has always represented a challenge for preoperative patients due to the increased risk that comes with decreased hemoglobin levels. Different therapies and techniques have been developed to assist in the process of hemopoiesis such as administration of Epoetin alfa as well as to reduce postoperative blood loss by means of mechanical or chemical hemostasis methods. Although much success has come from the use of these therapies in the surgical setting, the question remains if such treatments could be used in the management of anemia following acute blood loss in the emergency department setting. Studies have shown significant decrease in mortality of patients with post-traumatic or post-partum hemorrhage who received tranexamic acid within 3 hours of bleed onset. Aggressive mechanical hemostasis has also shown to reduce the need for blood transplant by preventing blood loss and progressive anemia. Hospitals with a carefully developed blood-conservation protocol have attained decreased morbidity and mortality rates of bloodless patients and have established the foundations to what will soon be considered the new standard of care.

Thesis Overview

Research Problem

A particular ethical problem is presented to many surgeons caring for patients whom, due to either religious or personal reasons, refuse the use of blood products. Different devices and intraoperative techniques have been developed to salvage blood or to prevent blood loss in highly invasive procedures. Despite these advancements, the presence of anemia continues to represent a challenge for medical providers who wish to provide excellent care for these individuals while maintaining and respecting patient autonomy. A second problem is that since many of these techniques were developed for the surgical patient, many emergency providers may not be fully aware of the efficacy of such treatments and might therefore lean back on a more traditional, transfusion-oriented practice. This lack of knowledge could potentially limit the treatment opportunities for patients who refuse blood transfusions causing either a delay in their definitive care or exposing them to a poor choice of treatment with a higher risk of morbidity and mortality.

Research questions

Is there an increase in mortality for patients with preoperative anemia facing bloodless surgery when compared to those who receive allogenic blood transfusions? What are some techniques or treatments to decrease the risk in patients that undergo bloodless surgery? Can bloodless surgery be performed in cases of trauma or emergency?

Hypothesis

Preoperatively anemic patients undergoing bloodless cardiovascular surgery will have a higher mortality than those with normal blood counts.

Purpose of research

To identify risk and to describe different techniques used to manage preoperative anemia prior to bloodless surgical procedures and discuss the possible implementation of bloodless medicine in the emergency and urgent care setting.

Methodology

 Data for this research was acquired through peer reviewed journals such as British Journal of Anesthesia, American Family Physician and Journal of Cardiothoracic and Vascular Anesthesia. Articles were obtained online from different databases including Elsevier, EBSCO, PubMed and Science Direct by using keywords: “Bloodless Surgery”, “Bloodless Medicine”, “Preoperative Anemia”, “Anticoagulation management”. Databases were accessed through Nova Southeastern University’s HPD as well as University of Central Florida’s library access. Supplemental information was acquired by researching references cited in the original articles. UpToDate was consulted for latest guidelines on pharmacotherapies and procedures used in bloodless medicine.

Introduction

Bloodless medicine refers to the practice of caring for patients without the use of blood transfusions. Such practice encompasses a series of interventions that prepare the patient to undergo invasive procedures without the need for allogenic blood transfusions as well as postoperative support and techniques to minimize complications and improve patient outcome. The need for such practice is often attributed to a particular patient population who is known in the medical community for their refusal to accept blood products, namely, Jehovah’s Witnesses. However, the principles of bloodless medicine have expanded beyond religious values and are currently appealing to a large number of both patients and practitioners not associated with the Witness faith due to the reduced risk of transmissible infections and long-term complications associated with blood transfusions. In order to care for these patients while still respecting their wishes, many hospitals developed bloodless protocols, mostly for surgical patients whose hemoglobin count was low. Despite the success bloodless programs are having across the country, the question remains of whether or not such techniques can be applied successfully in the emergency setting. One of the objectives of this paper is to provide information about some treatment options and techniques used in the care for patients who refuse blood transfusions.

Techniques used in Bloodless medicine

Preoperative assessment

A detailed patient history coupled with a thorough physical examination will expose potential threats such as pre-existing bleeding disorders, cardiovascular disease or pulmonary disease that should be addressed and optimized preoperatively. When asking about medications, it is important to identify use of anticoagulants such as Warfarin, Heparin, Aspirin, NSAIDs and steroids and discontinue if at all possible. Recommended timeframe for discontinuation of anticoagulants varies from medication to medication. It is recommended for Warfarin to be discontinued 3 to 5 days prior to surgery while Aspirin and NSAIDS should be stopped a week prior to the procedure. When the patient is found to be on heparin on LMWH the risk of thromboembolism must be weighed against the risk of bleeding to determine bridge therapy. Figure 1 presents recommendations for bridge therapy as listed by the AAFP. (Du Breuil, 2007) Asking about the use of natural supplements is also important since some herbs such as Chamomile and Dandelion root are known to inhibit clotting while others such as Bilberry, Bromelain, Fish Oil, Flax seed oil, Gingko Biloba and Saw palmetto are known to decrease platelet aggregation and by extension coagulation.

Figure 1: Perioperative bridge therapy as recommended by AAFP (Du Breuil, 2017)

Hematopoiesis

The presence of pre-operative anemia represents a challenge when attempting bloodless surgery. Vaislic mentioned in his journal: “a preoperative hemoglobin concentration of less than 6 g/dL increases the risk of death 30 days after surgery by a factor of 26 relative to a concentration of 12 g/dL or greater in surgical patients who declined blood transfusions” (Vaislic, 2012). The supplementation of IV iron, Vitamin B12 and folate has been implemented for intermediate-risk and high-risk procedures that are elective approximately 6 weeks prior to the procedure in order to assist erythrocyte production. If the surgery is more immediate, recombinant human erythropoietin can be given in two different regimens depending on the time frame prior to the procedure. The first FDA-recommended regimen is 300 units/kg/day subcutaneously for 10 days prior to surgery, on the day of surgery and 4 days prior to surgery. The alternate regimen is 600 units/kg subcutaneously once weekly for 3 weeks before surgery and on the day of surgery (Goldberg, 1996). The goal of both regimens is to reach a hemoglobin level above 14 g/dL by the time of surgery. Prior to 1998, hospital protocol would not allow surgery for any patient with a hemoglobin level below 14 g/dL., however the use of erythropoietin has been implemented since for the use in such patients to increase hemoglobin levels preoperatively and reduce risk (Goldberg, 1996).

Intraoperative techniques

Hemodilution has proven beneficial when large volumes of blood are expected to be lost. Isovolemic hemodilution is a method of collecting multiple units of autologous blood preoperatively or intraoperatively and immediately replacing them with either a crystalloid or colloid solution. This technique dilutes circulating blood so that if bleeding were to occur only a smaller fraction of whole blood would be lost. Towards the end of the operation, the previously collected blood would be infused back into the patient replenishing the lost components (Bryson, 1998).

Get Help With Your Nursing Literature Review

If you need assistance with writing your nursing literature review, our professional nursing literature review writing service is here to help!

Nursing Literature Review Writing Service

The cell salvage approach involves the collection of lost blood using a double-lumen suction device. The suction device not only collects red blood cells, but also mixes the blood with a predetermined volume of heparin and saline to avoid coagulation as it transports the blood to a reservoir inside of the machine. Once the blood reaches the reservoir, erythrocytes are filtered through a semi-permeable membrane that removes waste products and other blood components. Once the cells are filtered, they are suspended in saline ready to be infused back into the patient. Erythrocytes may be stored up to six hours prior to transfusion. Figure 2 shows a basic diagram of how cell salvage machines operate (Ashworth, 2010)

Figure 2: Cell Salvage machine operates by collecting blood via a dual-lumen catheter that mixes the blood with heparinized saline as it transports the blood for filtration. Once filtrated the machine is capable of transfusing washed erythrocytes back into the patient (Ashworth, 2010)

Other intraoperative techniques involve the collaboration of the anesthesiologist since it has been shown that neuraxial or local anesthesia is associated with less blood loss. Some anesthesia can also be used to maintain low blood pressures of 80-90 mm Hg systolic as well as a mean arterial pressure of around 50-65 mm Hg to prevent excessive postoperative blood loss. Lastly it has been known that hypercapnia and increased intrathoracic pressure increases blood loss, therefore the method of ventilation for the surgical patient should be considered carefully.

Postoperative management of blood loss

Postoperative blood loss can increase morbidity and mortality for patients who refuse blood transfusions depending on how far their hemoglobin level drops. Physiologic effects occur when hemoglobin levels reach 9-10 g/dL whereas a hemoglobin level of 2.1-3.0 g/dL is associated with a 54% mortality and a hemoglobin level of 1.1-2.0 g/dL is associated with a 100% mortality. These figures mark the importance of controlling postoperative bleeds as soon as possible. While the use of colloid and crystalloid solutions may help the hypovolemic patient, they cannot substitute blood in the oxygenation of vital tissues (Cotton, 2006). Overuse of such solutions has been associated with coagulopathy and organ disfunction (Cotton, 2006). Prolonged hypertension should be avoided to decrease risk of massive hemorrhage. Blood tests should be kept to a minimum, and if needed, microtubes should be used for collection only. If coagulopathies are present, vitamin K can be given orally at a dose of 10mg unless condition is critical and requires intravenous vitamin K at a rate of 10 mg infused over 30 minutes repeated every 12 hours if needed (Wilkerson, 1988). If bleeding is severe, or if hepatic pathology or injury is present, the first proteins to become deficient is fibrinogen. Because fibrinogen plays a crucial role in clot stabilization and platelet aggregation, a decrease of fibrinogen represents a severe complication in patients who refuse transfusions and should be treated with the administration of cryoprecipitate. Cryoprecipitate is acquired from frozen plasma and it contains fibrinogen, factor VIII, Von Willebrand factor, factor XIII and fibronectin (Curry, 2016). Since cryoprecipitate is composed of blood fractions rather than whole blood, some patients of the JW faith may be more inclined to accept such treatment while others might reject it as well. Prophylactic treatment against infections can also prove beneficial in the postoperative anemic patient since sepsis increases metabolic rates and by extension oxygen consumption.

Bloodless Medicine and Emergency care

The techniques discussed above have been applied to emergency settings by different bloodless programs established in hospitals across the country. These programs have shown much success in lowering mortality by providing different treatment options when transfusions are refused. A multidisciplinary approach including surgeons, nurses, blood bank representatives as well as good communication with patients to allow verbalization of preferred medical treatments has assisted these programs in their success. These programs expand­­ their bloodless protocol to include emergency patients that may be anemic or hypovolemic due to acute blood loss. Although acute blood loss can occur due to a wide variety of disease conditions, from gastrointestinal bleed to malignancy. Since some of the bloodless treatments regimens that are successful in the surgical patient require certain time to take effect, we should focus on emergency situations that do not allow for time to see if bloodless medicine can indeed provide a similar outcome as those who receive transfusions. Therefore we will focus on emergency situations that result in active hemorrhage: trauma and post-partum hemorrhage.

Bloodless Medicine and Traumatic anemia

Trauma claims 5 million lives every year making it a leading cause of mortality worldwide. The main contributing factor for such high mortality is hemorrhage. Bloodless medicine in the trauma setting becomes a major challenge for trauma physicians since survival of the patient depends highly on rapid identification and cessation of hemorrhage to prevent progressive anemia and death. Fluid resuscitation, rapid hemostasis, treatment of coagulopathies and discontinuation of drugs that prevent coagulation should all be applied to the trauma patient. The use of epoetin alfa has shown a reduced mortality in trauma patients but is also associated with an increase thrombosis, therefore its use might be considered in a case-by-case scenario (Corwin, 2007). The use of the antifibrinolytic tranexamic acid (TXA) in the trauma setting was studied with a randomized trial of 20,000 trauma patients known as the CRASH-2 trial. It was found that administration TXA showed reduction in hemorrhage-related mortality if given within 3 hours from onset of trauma when compared to a placebo. TXA is even available in some prehospital emergency units due to its efficacy in preventing bleeding (Roberts, 2013). A retrospective study of Jehovah’s Witness patients in the ICU following major trauma showed no significant difference in morbidity or mortality with patients who accepted transfusions (Georgiou, 2009) A prior retrospective study conducted in 2003 showed that Jehovah’s Witnesses do not have increased mortality after major trauma compared with patients that do accept transfusions (Varela 2003). This data suggests that the use of post-traumatic transfusions is not a determining factor in reduced mortality and therefore a bloodless approach focused on rapid hemostasis can indeed be successful in a trauma setting.

Bloodless Medicine and Anemia in Pregnancy

The leading cause of maternal mortality is postpartum hemorrhage and occurs when blood loss exceeds 500 mL following child birth. Careful prepartum preparation with an obstetric doctor with experience in high risk pregnancies, at a care center where bloodless therapies are available is recommended. Specific nutrition, supplementation and coordination among the providers caring for the patient can prevent complications from postpartum hemorrhage (Scharman, 2017). However, in the emergency setting, medical providers might have to improvise to assist emergent deliveries in patients who refuse transfusions. Generally, postpartum hemorrhage is managed much like a traumatic hemorrhage. Management includes IV fluids and blood products, uterotonics, removal of retained products of contraception, genital laceration repair, and maneuvers including fundal massage (Scharman, 2017). If bleeding is not controlled, invasive procedures such as balloon tamponade, uterine artery embolization may be performed. If uterine bleeding remains uncontrolled, peripartum hysterectomy may be performed as a last-resort procedure if other interventions fail (Sentilhes, 2016).

Find Out How NursingAnswers.net Can Help You!

Our academic experts are ready and waiting to assist with any writing project you may have. From simple essay plans, through to full dissertations, you can guarantee we have a service perfectly matched to your needs.

View our academic writing services

Antifibrinolytics such as tranexamic acid can also be used in postpartum hemorrhage. Multiple studies show that in addition to uterotonics, tranexamic acid decreases postpartum bleeding reducing the need for blood transfusion after vaginal birth or caesarean section in women at low-risk for PPH (Simonazzi, 2016). The World Maternal Antifibrinolytic (WOMAN) trial published a large randomized-controlled trial of over 20,000 women with postpartum hemorrhage and showed that treatment with tranexamic acid significantly reduced mortality with no thromboembolic side effects when given to the patient within 3 hours postpartum. (WOMAN, 2017). Although routine treatment with tranexamic acid is not recommended, it provides an alternative to reduce bleeding risks in patients who refuse transfusions.

Discussion

Literature Strengths

 The literature used in this research included case reports, retrospective case studies, and randomized trials for effectiveness of particular therapies. Some of the case studies describe over 20 years of experience with bloodless medicine and the case reports mentioned involve successful outcomes of bloodless medicine in patients that underwent very different procedures. Research includes outcomes for patients that underwent aortic dissections, heart valve replacement, tumor resection, coronary artery bypass grafting, etc. These procedures are highly invasive and because of it, they support the claim that bloodless medicine is capable of handling even hemodynamically compromising procedures. The purpose of the article wasn’t to prove causality, but to share with the reader techniques that have been useful in the surgical setting and can also be useful in the emergency setting. The wide variety of journals and articles referenced helps to support that claim.

Literature Weaknesses

 When it comes to the main question of bloodless medicine vs allogenic blood transfusion, there was no literature that presented a randomized controlled trial. Most of the information was gathered as a either a retrospective case study or as case reports. Most of these cases were reported due to the success of the procedure involved while practicing bloodless medicine, however there is no way of knowing the amount of cases that resulted in failure. Many articles used in this research date past 5 years. Developments of newer techniques as well as updates on the techniques mentioned could be missing.

Recommendations for Future research

 A randomized controlled trial to compare bloodless medicine and allogenic blood transfusions would be time consuming, expensive and unethical. To properly assess the differences in outcomes between these two types of treatments a more controlled retrospective study could be conducted across several hospitals in the United States. In this study, patients who refuse transfusions are closely matched with patients of similar age, gender, ethnicity and complaint. A prospective study could even be attempted in which patients who received bloodless treatment are followed up on for a designated amount of time to assess for complications morbidity and compare to their matched counterparts who received transfusions.

Implications for the PA profession 

One of the roles of surgical physician assistants is to perform pre-op and post-op patient rounds. Their role is crucial for identification of anemia prior to surgery. Likewise, emergency and urgent care Physician Assistants play a key role in the care of anemic patients who refuse blood products but could benefit from alternative therapies. Determining the mortality risk increase can potentially provide insight on the importance of managing the blood count of such patients prior to bloodless surgery. It could also lead to protocols that include nutritional and pharmaceutical prepping ordered by the physician assistant to increase blood counts. This will help decrease both the workload for the surgeon and, most importantly, mortality risk for this patient population. 

Conclusion

­­Although originally the concept of bloodless medicine was established to care for a very limited population, the results that followed showed bloodless medicine to be a good alternative to the use of allogenic blood transfusions. Studies have shown that using multimodal blood conservation strategies result in similar hemoglobin concentrations with similar or even improved outcomes and reduced costs. Even in the case of acute blood loss, blood conservation strategies can prevent the need for blood transfusions and should therefore be attempted in all patients. Due to the national shortage of blood available for transfusion and based on the research referenced, it is recommended for all providers to consider and to offer blood conservation treatments to all patients. As medical advancements continue, the concept of bloodless medicine will likely become the next standard of care.

References

• Vaislic CD, Dalibon N, Ponzio O, et al. Outcomes in cardiac surgery in 500 consecutive Jehovahs Witness patients: 21 year Experience. Journal of Cardiothoracic Surgery. 2012;7(1). doi:10.1186/1749-8090-7-95
• Du Breuil AL, Umland EM. Outpatient Management of Anticoagulation Therapy. American Family Physician. 2007;75(7):1031-1042. https://www.aafp.org/afp/2007/0401/p1031.html. Accessed July 8, 2019.
• Goldberg MA, McCutchen JW, Jove M, et al. A safety and efficacy comparison study of two dosing regimens of epoetin alfa in patients undergoing major orthopedic surgery. Am J Orthop (Belle Mead, NJ). 1996;25(8):544–552.
• Bryson GL, Laupacis A, Wells GA. Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The international study of perioperative transfusion. Anesth Analg. 1998;86(1):9–15.
• Ashworth A, Klein AA. Cell Salvage as a Part of Blood Conservation Strategy in Anaesthesia. Survey of Anesthesiology. 2010;55(3):401-416. doi:10.1097/01.sa.0000395991.42078.c0
• Cotton BA, Guy JS, Morris JA Jr, Abumrad NN. The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock. 2006;26(2):115–121.
• Wilkerson DK, Rosen AL, Sehgal LR, Gould SA, Sehgal HL, Moss GS. Limits of cardiac compensation in anemic baboons. Surgery. 1988;103(6):665–670.
• Curry N, Wong H. Cryoprecipitate transfusion: current perspectives. International Journal of Clinical Transfusion Medicine. 2016;Volume 4:89-97. doi:10.2147/ijctm.s99042
• Corwin HL, Gettinger A, Fabian TC, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007;357(10): 965–976.
• Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomized controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013;17(10):1):79
• Georgiou C, Inaba K, DuBose J, et al. Optimizing outcomes in the Jehovah’s witness following trauma: special management concerns for a unique population. Eur J Trauma Emerg Surg. 2009;35(4):383
• Varela JE, Gomez-Marin O, Fleming LE, Cohn SM. The risk of death for Jehovah’s Witnesses after major trauma. J Trauma. 2003;54(5):967–972.
• Scharman CD, Shatzel JJ, Deloughery TG. The Rise Of Bloodless Medicine: How We Treat Those Who Cannot Receive Blood Products for Religious Or Other Reasons. Science Trends. November 2017. doi:10.31988/scitrends.6324
• Sentilhes L, Merlot B, Madar H, Sztark F, Brun S, Deneux-Tharaux C. Postpartum haemorrhage: prevention and treatment. Expert Rev Hematol. 2016;9(11):1043–1061.
• Simonazzi G, Bisulli M, Saccone G, Moro E, Marshall A, Berghella V. Tranexamic acid for preventing postpartum blood loss after cesarean delivery: a systematic review and meta-analysis of randomized con- trolled trials. Acta Obstet Gynecol Scand. 2016;95(1):28–37.
• Effect of early tranexamic acid administration on mortality, hysterec- tomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-con- trolled trial. Lancet (London, England). 2017;389(10084):2105–2116.
• Auron M, Castillo MYD. Preoperative anemia optimization: role of iron supplementation. Journal of Xiangya Medicine. 2018;3:37-37. doi:10.21037/jxym.2018.09.05
• Bryson GL, Laupacis A, Wells GA. Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta- analysis. The international study of perioperative transfusion. Anesth Analg. 1998;86(1):9–15.
• Carson JL. The Limits of Bloodless Surgery. Transfusion Alternatives in Transfusion Medicine. 2005;6(3):52-55. doi:10.1111/j.1778-428x.2005.tb00124.x
• Casati V, D’Angelo A, Barbato L, et al. Perioperative management of four anaemic female Jehovah’s Witnesses undergoing urgent complex cardiac surgery. British Journal of Anaesthesia. 2007;99(3):349-352. doi:10.1093/bja/aem170
• Crum E, Valenti J. Can a bloodless surgery program work in the trauma setting? Nursing. 2007;37(3):54-56. doi:10.1097/01.NURSE.0000261830.65919.4c.
• Esper SA, Waters JH. Intra-operative cell salvage: a fresh look at the indications and contraindications. Blood Transfus. 2011;9(2):139–147. doi:10.2450/2011.0081-10
• Frank SM, Wick EC, Dezern AE, et al. Risk-adjusted clinical outcomes in patients enrolled in a bloodless program. Transfusion. 2014;54(10pt2):2668-2677. doi:10.1111/trf.12752
• Gaddie K, Montgomery C, Murphy S, et al. Management of bloodless surgery in a trauma setting. Balancing patient wishes with safety. Minnesota Medicine. 2013;96(6):49-51. http://search.ebscohost.com.ezproxylocal.library.nova.edu/login.aspx?direct=true&db=mnh&AN=23862373&site=eds-live. Accessed June 11, 2019
• Gohel MS, Bulbulia RA, Slim FJ, Poskitt KR, Whyman MR. How to approach major surgery where patients refuse blood transfusion (including Jehovah’s Witnesses). Ann R Coll Surg Engl. 2005;87(1):3–14. doi:10.1308/1478708051414
• Henderson R, Chow JH, Tanaka KA. A Bridge to Bloodless Surgery: Use of Hemoglobin-Based Oxygen Carrier for Anemia Treatment and Autologous Blood Preservation During Redo Pulmonic Valve Replacement. Journal of Cardiothoracic and Vascular Anesthesia. 2019;33(7):1973-1976. doi:10.1053/j.jvca.2018.09.036
• Ito Y, Nakamura Y, Tagusari O, Yoshida S. Repeat Minimally Invasive Mitral Valve Replacement for Recurrent Mitral Stenosis after OMC in Patients Who Decline Blood Product Transfusion for Religious Reasons. Case Reports in Surgery. 2015;2015:1-4. doi:10.1155/2015/239197
• Mirzaei S, Hershberger PE, Devon HA. Association Between Adverse Clinical Outcomes After Coronary Artery Bypass Grafting and Perioperative Blood Transfusions. Critical Care Nurse. 2019;39(1):26-35. doi:10.4037/ccn2019589
• Olshove VF, Preston T, Gomez D, Phillips A, Galantowicz M. Perfusion Techniques Toward Bloodless Pediatric Open Heart Surgery. The Journal of ExtraCorporeal Technology. 2010;42:122-127. http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4680035&blobtype=pdf.
• Olshove V, Berndsen N, Sivarajan V, Nawathe P, Phillips A. Comprehensive blood conservation program in a new congenital cardiac surgical program allows bloodless surgery for the Jehovah Witness and a reduction for all patients. Perfusion. 2017;33(3):194-202. doi:10.1177/0267659117733810
• Pasic M, Ruisz W, Koster A, Hetzer R. Bloodless Surgery of Acute Type A Aortic Dissection in a Jehovah’s Witness Patient. The Annals of Thoracic Surgery. 2005;80(4):1507-1510. doi:10.1016/j.athoracsur.2004.03.044
• Resar LMS, Frank SM. Bloodless medicine: what to do when you can’t transfuse. Hematology. 2014;2014(1):553-558. doi:10.1182/asheducation-2014.1.553
• Scha¨lte G, Janz H, Busse J, Jovanovic V, Rossaint R, Kuhlen R. Life-threatening postoperative blood loss in a Jehovahs Witness, treated with high-dose erythropoietin. British Journal of Anaesthesia. 2005;94(4):442-444. doi:10.1093/bja/aei068
• Tokin C. Blood-Management Programs: A Clinical and Administrative Model with Program Implementation Strategies. The Permanente Journal. 2009;13(1):18-28. doi:10.7812/tpp/08-029
• Whitson BA, Huddleston SJ, Savik K, Shumway SJ. Bloodless Cardiac Surgery is Associated With Decreased Morbidity and Mortality. Journal of Cardiac Surgery. 2007;22(5):373-378.doi:10.1111/j.1540-8191.2007.00428.x.