All Patients Patients Accepting Blood Transfusions Jehovah's Witness oncology patients

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1 Management of the Jehovah's Witness Oncology Patient: Perspective of the Transfusion Service Kaaron Benson, MD Pathology Service, H. Lee Moffitt Cancer Center & Research Institute. Due to refusal of blood component transfusions, Jehovah's Witness patients with cancer present a challenge to oncologists who must find appropriate and acceptable treatments. In order to assess the morbidity and mortality that these patients suffer, a retrospective review was conducted of all 58 Jehovah's Witness patients treated at our center from October 1986 through February This study showed that (1) younger Jehovah's Witness patients or their parents were more likely to accept blood transfusion than older Jehovah's Witness patients, (2) considerable risk of acute morbidity and mortality occurred in patients who refused blood when blood transfusions were indicated, and (3) long-term prognosis may be worsened for some Jehovah's Witness patients due to limited treatment provided in those with anemia or with anticipated anemia. Introduction Treatment of cancer with chemotherapy and surgery often requires blood component support. The availability of large numbers of platelet components beginning in the late 1960s revolutionized the care of oncology patients by allowing the administration of higher doses of chemotherapy. Red blood cell transfusions are crucial to many oncologic surgical procedures associated with acute blood loss. Jehovah's Witness patients with cancer present a unique challenge due to their refusal to accept allogeneic and some forms of autologous blood transfusions. The religion now called Jehovah's Witnesses was organized by Charles Taze Russell in the 1870s in Pennsylvania. Russell's group initially was known as "Zion's Watch Tower Tract Society" and currently is referred to as "Watchtower Bible and Tract Society." In 1931, the organization officially became known as the "Jehovah's Witnesses."[1] Members of the Jehovah's Witness religion do not salute flags, join service organizations, enlist in the military, vote in public elections, or take any interest in civil government. Their beliefs regarding blood transfusion, which were not stated publicly until 1945, are based on a literal interpretation of the Old Testament. One commonly cited reference used to explain their refusal of blood transfusions states, "For it [the blood] is the life of all flesh; the blood of it is for the life thereof; therefore I say unto the children of Israel, ye shall eat the blood of no manner of flesh: for the life of all flesh is the blood thereof. Whoever eateth it shall be cut off." (Leviticus 17:14) Jehovah's Witnesses believe that God has forbidden them to "eat blood," and blood transfusions are analogous to eating blood. While opposing blood transfusions on religious grounds, they are eloquent in their discussions of blood transfusion hazards, yet fail to mention the benefits of transfusion.[2] Interestingly, their faith permits the consumption of animal meat. Jehovah's Witnesses usually will refuse all whole blood and blood component transfusions, such as red blood cells, platelets, fresh frozen plasma, cryoprecipitate, or stem cells. To determine the morbidity and mortality associated with the refusal to receive blood transfusions, a retrospective review was performed on a population of Jehovah's Witness oncology patients who were treated at our center. Materials and Methods Inpatient and outpatient data were reviewed on all Jehovah's Witness patients who were admitted to our institution from October 1986 through February Recorded information included patient demographic data, diagnosis, lowest hemoglobin level, maximum estimated blood loss for surgical patients, treatments received, and what treatments, if any, were discontinued, diminished in scope, or not performed due to the patient's refusal of blood. In addition, morbidity or mortality related to this noncompliance was recorded. Results A total of 58 Jehovah's Witness oncology patients were treated in the 7.5year period (Table 1). Although the median patient age at the time of diagnosis was 54 years, the ages ranged from one year to 90 years. There were almost twice as many women as men patients (37 vs 21, respectively). "Female" cancers (breast, cervical, endometrial, vulvar, vaginal, and ovarian) were diagnosed in 21 (57%) women, while "male" cancer (prostate) was diagnosed in one (5%) man. Table 1. Comparison of All Jehovah's Witness Oncology Patients and Those Who A ccepted Blood Transfusions* All Patients Patients Accepting Blood Transfusions Jehovah's Witness oncology patients 58 6 Median age at diagnosis Age range Woman:man ratio 1.8:1 1:2 * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February 1994.

2 Six (10.3%) of the 58 Jehovah's Witness patients in our study accepted blood transfusions or, for minors, their parents accepted transfusions for them. The median age at the time of diagnosis for this group (18 years) was substantially less than the median age of those refusing transfusion (58 years) and less than the median age (44 years) of those refusing blood but with indications for transfusion. All patients who accepted transfusions received allogeneic red blood cell transfusions, and two patients also received platelets. One patient received only autologous and directed donor red blood cell units. No other blood components were transfused, and no patient received albumin or any other blood derivative. Many of the anemic patients accepted and received recombinant human erythropoietin (rhepo). Of the seven Jehovah's Witness patients who were 21 years of age or younger, five accepted blood transfusions, one did not require blood, and one refused blood (Table 2). No court orders were required to legally permit transfusions, although this was considered for a fouryearold girl with Wilms' tumor. Table 2. All Jehovah's Witness Oncology Patients 21 Years of Age or Younger* Age Sex Diagnosis Transfusion Accepted 1 M Acute lymphocytic leukemia Yes 19 M Sarcoma Yes 3 M Wilm's Tumor Yes 21 M Gastric cancer ** 17 M Acute lymphocytic leukemia Yes 21 F Sarcoma Yes 4 F Wilm's Tumor No * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February ** No transfusions required. Nine patients in our study had indications for transfusion of red blood cells but refused transfusions (Table 3). These indications included a hemoglobin level of less than 8.0 g/dl, an estimated blood loss of more than 750 ml at the time of surgery, or unfavorable signs and/or symptoms related to the anemia. A 69yearold woman with ovarian cancer suffered a cerebrovascular accident following a supracervical hysterectomy, bilateral salpingo oophorectomy with an estimated blood loss of 1800 ml. Her lowest recorded hemoglobin level was 7.5 g/dl. A 25yearold woman with chronic lymphocytic leukemia died of anemia and thrombocytopenia, both correctable with blood transfusion. No other patient suffered any acute morbidity or mortality related to the refusal of blood. Table 3. Jehovah's Witness Oncology Patients With Indications for Transfusi on Who Refused Blood* Age Sex Lowest Hemoglobin Level (g/dl) 80 F F Estimated Blood Loss (ml) 25 F 6.5** (No surgery performed) 69 F 7.5** 1800*** 24 F M 6.9 (No surgery performed) 42 F 7.7 (No surgery performed) 58 M F 7.5 (No surgery performed) * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February ** Patient died of anemia and thrombocytopenia. *** Patient suffered a postoperative cerebrovascular accident. Many of these Jehovah's Witness patients received abbreviated medical care as a result of the refusal of blood (Table 4). Ten patients underwent restricted treatments: surgery was not performed or limited in scope, chemotherapy was withheld or administered at lower dosages, or further radiation therapy was withheld because of the presence of significant anemia. The woman with chronic lymphocytic leukemia developed a bleeding peptic ulcer but was not considered a surgical candidate due to her existing anemia. Table 4. Jehovah's Witness Oncology Patients With Limited Treatment Due to Refusal of Blood* Age Sex Diagnosis Surgery Not Performed or Limited Chemotherapy Withheld or Dose Lowered 70 M Prostate cancer 44 F Ovarian cancer Radiation Therapy Withheld

3 25 F Chronic lymphocytic leukemia 40 F Endometrial cancer 66 M Lymphoma 77 M Renal cell cancer 56 M Waldenstrom's macroglobulinemia 27 M Lymphoma 37 F Cervical cancer 71 F Breast cancer * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February Discussion Many of the treatment modalities used for oncology patients result in marrow suppression or in the loss of red blood cells. Without blood component support, patients may suffer adverse consequences. Of the 58 Jehovah's Witness oncology patients in this study, one suffered acute adverse effects, one patient died, and 10 may have had worsened prognoses due to abbreviated treatments. While the median age of this total group of patients was 54 years, the median age of the group who received transfusions was 18 years. Of the six patients under age 22 who required transfusions, five (83%) received transfusions. Therefore, while most adult Jehovah's Witness patients were unwilling to accept blood for themselves, most Jehovah's Witness parents permitted transfusions for their minor children, and many of the young adult patients also were willing to accept transfusions forthemselves. Table 5. Blood, Blood Components, Blood Derivatives, and Procedures Accepted and Refused by Jehovah's Witness Patients Usually Related Whole blood Red blood cells Platelets Fresh frozen plasma Cryoprecipitated antihemophilic factor Granulocytes Fibrin glue/sealant Predeposited autologous blood/components Usually Accepted Normovolemic hemodilution* Intraoperative red blood cell salvage* Erythropoietin** Hemodialysis*** Heart-lung equipment*** Individual Decision Albumin Immune globulins Factor concentrates Organ and tissue transplants * Usually accepted if patient remains in contact with blood. ** Synthetic hormone suspended in albumin. *** Provided that a non-blood prime is used. Jehovah's Witness patients want quality medical care and will accept all medical procedures except blood transfusions.[2] Specifically, they refuse transfusion of all blood and blood components (Table 5). Products derived from pooled human plasma are termed blood derivatives and include albumin and immune globulins. The blood derivatives are not absolutely prohibited, and each Jehovah's Witness patient must decide individually whether to accept these.[3] Some vaccines and medications such as erythropoietin are suspended in a small amount of albumin and are usually accepted by Jehovah's Witness patients. The religion also permits organ and tissue transplants for those individuals who allow it. For members of the Jehovah's Witness religion, allogeneic blood components are unacceptable in any form, and autologous blood usually will be accepted only if it has been kept in continuous contact with the patient's blood. Therefore, predeposited autologous blood will be refused, but normovolemic hemodilution and intraoperative red blood cell salvage will be accepted if modified to allow a continuous circuit from the patient to the intravenous tubing and the blood bag. Kelley et al[4] described their use of red blood cell salvage equipment to create an unbroken flow of blood from the operative site to the cell separator, to the blood bag, and to the patient's peripheral circulation. The consequence of this refusal of blood has not been as perilous as anticipated. In a review[5] of 16 reported surgical series of Jehovah's Witness patients who underwent 1404 surgical procedures that normally required blood transfusion, the data indicated that only 0.5% to 1.5% of such operations were complicated by anemia that resulted in death. Spence et al[6] concluded that elective cardiovascular surgery can be performed safely without the use of allogeneic blood transfusion or predeposited autologous blood. Intraoperative salvage of red blood cells alone provided patients with sufficient oxygencarrying capacity to eliminate the need for other red blood cell transfusions during these surgical procedures. The treatment of oncology patients who refuse blood may be more hazardous than other clinical situations. Of the nine patients reviewed at our center who had indications for blood transfusion and refused blood, one died of anemia and thrombocytopenia, and one had a cerebrovascular accident. Of the 58 oncology patients studied, 10 had limited treatments due to their refusal of blood and presumably suffered longterm adverse consequences due to that restricted therapy. Jehovah's Witnesses have challenged the traditional approach to transfusion therapy. While many clinicians would consider red blood cell transfusions for a patient with a hemoglobin level of less than 7 or 8 g/dl, it appears that acute morbidity and mortality generally does not occur in this patient population until the hemoglobin drops below 5 or 6 g/dl.[7,8] Anecdotally, one Jehovah's Witness patient survived with a hemoglobin level as low as 1.4 g/dl.[7]

4 The transfusion of red blood cells and platelets is an important factor in the care of oncology patients. For patients who cannot accept this procedure, other strategies must be considered. Alternative approaches in the management of anemia and thrombocytopenia have been reviewed[9] (Table 6). The health care team should minimize the amount of iatrogenic red blood cells lost for laboratory testing. Intraoperative blood loss can be reduced with hemodilution and red cell salvage techniques. "Bloodless" surgery has been advocated as an additional technique that relies on meticulous surgical technique.[10] A patient's own red blood cell production can be enhanced with the use of rhepo; iron, vitamin B12, and folate must be provided for patients deficient in these nutrients. For the thrombocytopenic patient, synthetic agents such as desmopressin (DDAVP) and the antifibrinolytic agents (aminocaproic acid, tranexamic acid) can prevent or manage bleeding in certain clinical situations. Table 6. Clinical Management of Anemic Jehovah's Witness Patients Strategy Minimize iatrogenic blood loss Minimize intraoperative red blood cell loss Achieved by Elimination of unnecessary testing Reduction of test sample volume Normovolemic hemodilution Intraoperative salvage of red blood cells "Bloodless" surgery Enhance red blood cell production Erythropoietin Iron, vitamin B12, folate in deficient patients Ensure hemostasis (either prophylactically or therapeutically) Maintain blood volume Desmopressin Antifibrinolytic agents Aprotinin Crystalloid solutions Synthetic colloid solutions A critical aspect in the support of the bleeding patient is the maintenance of a normovolemic status. The Watchtower[2] specifies the various solutions (eg, normal saline, dextran, lactated Ringer's solution, and hetastarch) that are available to Jehovah's Witness patients. Desmopressin and aprotinin also have been used intraoperatively to reduce blood loss.[10] Substitutes for red blood cells that will be available in the future would be acceptable to Jehovah's Witness patients unless the product were derived from human blood, and even then the product may be accepted. A number of legal issues must be considered by the health care team caring for a Jehovah's Witness patient.[11,12] A competent adult patient can refuse treatment, and that refusal should be documented. An advance directive specifying that the patient refuses blood transfusions, even to the point of death, should be signed, dated, and witnessed, and this information should be available on the patient's chart. Most Jehovah's Witness patients carry advance directives with them and update them regularly. While court decisions have generally upheld the adult's right to refuse blood transfusions, the laws regarding a parent's right to refuse blood transfusions for themselves or for their minor children vary from state to state with the majority of courts taking the position that the state's interest in promoting the health and welfare of children justifies compulsory medical care when necessary to save the life of a pregnant woman or the mother of a young child. Every state has a mechanism to seek judicial intervention when a parent of a minor child refuses to consent to necessary treatment of themselves or of a minor child.[1113] The courts have upheld parents' decisions to refuse blood transfusions when the remaining parent, a family member, or a friend would be able to care for the minor children if the patient died.[10] Conclusions Jehovah's Witness oncology patients will accept virtually all medical treatments. When patients refuse transfusion of blood and blood components, physicians need to discuss the risks associated with that refusal, as well as the potential alternatives to standard blood transfusion. While physicians are taught to preserve life, they also must respect a patient's right to refuse individual treatments. By offering alternative therapies, physicians treating Jehovah's Witness patients generally will be able to realize both their own goals as well as those of their patients. References 1. Blajchman MA. Transfusionrelated issues in Jehovah's Witness patients. Transfus Med Rev. 1991;5: Anonymous. How can blood save your life? Watchtower Bible and Tract Society of New York. Brooklyn, NY: Anonymous. Will the future fulfill your hopes? Watchtower Bible and Tract Society of New York. Brooklyn, NY: Kelley JL, Burke TW, Lichtiger B, et al. Extracorporeal circulation as a blood conservation technique for extensive pelvic operations. J Am Coll Surg. 1994;178: Kitchens CS. Are transfusions overrated? Surgical outcome of Jehovah's Witnesses. Am J Med. 1993;94: Spence RK, Alexander JB, DelRossi AJ, et al. Transfusion guidelines for cardiovascular surgery: lessons learned from operations in Jehovah's Witnesses. J Vasc Surg. 1992;16: Viele MK, Weinkopf RB. What can we learn about the need for transfusion from patients who refuse blood? The experience with Jehovah's Witnesses. Transfusion. 1994;34: Spence RK, Carson JA, Poses R, et al. Elective surgery without transfusion: influence of preoperative hemoglobin level and blood loss on mortality. Am J Surg. 1990;159: Mann MC, Votto J, Kambe J, et al. Management of the severely anemic patient who refuses transfusion: lessons learned during the care of a Jehovah's Witness. Ann Intern Med. 1992;117: Spence RK. The status of bloodless surgery. Transfus Med Rev. 1991;5: Kleinman I. Written advance directives refusing blood transfusion: ethical and legal considerations. Am J Med. 1994;96: Goldman EB, Oberman HA. Legal aspects of transfusion of Jehovah's Witnesses. Transfus Med Rev. 1991;5: Benson KT. The Jehovah's Witness patient: considerations for the anesthesiologist. Anesth Analg. 1989;69: Table 1. Jehovah's Witness Oncology Patients: All Patients Compared to Those Who Accepted Blood Transfusions* All Jehovah's Witness Cancer Patients Total number of patients 58 Median age at diagnosis 54 Age range 1 90 Woman:man ratio 1.8:1 Jehovah's Witness Cancer Patients

5 Accepting Blood Transfusion Total number of patients 6 Median age at diagnosis 18 Age range 1 52 Woman:man ratio 1:2 * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February 1994.Table 2. Patients 21 Years of Age or Younger Accepting or Rejecting Blood* Age Sex Diagnosis Transfusion Accepted 1 M Acute lymphocytic leukemia Yes 19 M Sarcoma Yes 3 M Wilms' tumor Yes 21 M Gastric cancer ** 17 M Acute lymphocytic leukemia Yes 21 F Sarcoma Yes 4 F Wilms' tumor No * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February ** No transfusions required.table 3. Jehovah's Witness Oncology Patients With Indications for Transfusion Who Refused Blood* Age Sex Lowest Hemoglobin Estimated Blood Loss (ml) Level (g/dl) 80 F F F 6.5** (No surgery performed) 69 F *** 24 F M 6.9 (No surgery performed) 42 F 7.7 (No surgery performed)58 M F 7.5 (No surgery performed) * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February ** Patient died of anemia and thrombocytopenia. *** Patient suffered a postoperative cerebrovascular accident.table 4. Jehovah's Witness Oncology Patients With Limited Treatment Due to Refusal of Blood* Age Sex Diagnosis Surgery Not Performed Chemotherapy Withheld Radiation Therapy or Limited or Doses Lowered Withheld 70 M Prostate cancer x x 44 F Ovarian cancer x 25 F Chronic lymphocytic x x leukemia 40 F Endometrial cancer x 66 M Lymphoma x 77 M Renal cell cancer x 56 M Waldenstrom's x macroglobulinemia 27 M Lymphoma x 37 F Cervical cancer x 71 F Breast cancer x * Treated at H. Lee Moffitt Cancer Center & Research Institute from October 1986 through February Table 5. Blood, Blood Components, Blood Derivatives, and Procedures Accepted and Refused by Jehovah's Witness Patients Usually Refused Whole blood Red blood cells Platelets Fresh frozen plasma Cryoprecipitated antihemophilic factor Granulocytes Fibrin glue/sealant Predeposited autologous blood/componentsusually Accepted Normovolemic hemodilution* Intraoperative red blood cell salvage* Erythropoietin** Hemodialysis*** Heartlung equipment*** Individual Decision Albumin Immune globulins Factor concentrates Organ and tissue transplants * Usually accepted if patient remains in contact with blood. ** Synthetic hormone suspended in albumin. *** Provided that a nonblood prime is used.table 6. Clinical Management of Anemic Jehovah's Witness Patients Strategy Achieved by Minimize iatrogenic blood loss Elimination of unnecessary testing Reduction of test sample volume Minimize intraoperative red Normovolemic hemodilution blood cell loss Intraoperative salvage of red blood cells "Bloodless" surgery Enhance red blood cell production Erythropoietin Iron, vitamin B12, folate in deficient patients Ensure hemostasis (either Desmopressin prophylactically or therapeutically) Antifibrinolytic agents Aprotinin Maintain blood volume Crystalloid solutions Synthetic colloid solutions