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Caring for Jehovah's Witness Patients Undergoing Complex Cardiac Surgery

Published:January 04, 2023DOI:https://doi.org/10.1053/j.jvca.2022.12.029
      The transfusion of blood products is common in cardiac surgery. Jehovah's Witness (JW) patients generally do not accept the transfusion of “primary blood components” including allogeneic red blood cells (RBCs), platelets, and fresh frozen plasma on religious grounds. Cardiac surgery in patients refusing blood products represents a unique challenge for the cardiovascular anesthesiologist and intensivist, potentially resulting in a conflict between the patient's independence and the physician's duty to save the patient's life.
      • Bolliger D
      • Sreeram G
      • Duncan A
      • et al.
      Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      • Muramoto O.
      Bioethical aspects of the recent changes in the policy of refusal of blood by Jehovah's witnesses.
      • Sniecinski R
      • Levy JH.
      What is blood and what is not? Caring for the Jehovah's Witness patient undergoing cardiac surgery.
      A recent review on the outcomes of cardiac surgery in JW patients concluded that the bloodless protocol for JW patients does not seem to significantly affect clinical outcomes when compared to non-JW patients with the possibility to transfuse blood products.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      This conclusion was mainly based on 11 comparative studies including >750 JW patients undergoing cardiac surgery between 1990 and 2018.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      Reported in-hospital mortality was 0%-to-19% in JW patients, and 0%-to-9% in control patients. Although there was no statistically significant difference in mortality within the included studies,
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      one study reported a 4- to 5-times higher in-hospital death rate in JW patients.
      • Valle FH
      • Pivatto Junior, F
      • Gomes BS
      • et al.
      Cardiac surgery in Jehovah's Witness patients: Experience of a Brazilian tertiary hospital.
      Furthermore, Chambault and colleagues reported that morbidity including re-surgery for bleeding, acute kidney injury, stroke, and myocardial infaction, was similar or even higher in the controls as compared to JW patients.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      Based on these findings, Chambault et al. suggested that the bloodless approach could potentially provide advantages to any patient undergoing cardiac surgery.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Helwani, et al. presented their experiences with JW patients undergoing cardiac surgery at their institution over a 20-year period in a retrospective cohort analysis.

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      They identified 48 adult JW patients, who were divided into a group with severe blood loss leading to anemia defined as any postoperative hematocrit <21% (n = 9) and a control group of patients with postoperative hematocrit ≥21% (n = 39). Postoperative anemia was associated with increased mortality at 30, 90, and 365 days after surgery and a trend to increased length of hospital stay.

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      The findings of the present study are of interest, as they partially questioned previous data that cardiac surgery in JW patients might be as safe as in non-JW patients.
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      In agreement with formerly reported survival,
      • Chambault AL
      • Brown LJ
      • Mellor S
      • et al.
      Outcomes of cardiac surgery in Jehovah's Witness patients: A review.
      1-year mortality was 0% in the group with postoperative hematocrit >21% in the present study. On the other hand, patients with hematocrit <21% had significantly worse outcomes, resulting in a 3-month mortality of 44%. In 3 out of 4 deaths, severe anemia appeared to be directly associated with cause of death (ie, stroke, multiorgan failure, cardiogenic shock).

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      This raises the question as to the safety margin of postoperative hemoglobin values. In 2 large randomized controlled studies including 7,250 patients, cardiac surgery patients were randomized to a liberal and a restrictive transfusion strategy.
      • Mazer CD
      • Whitlock RP
      • Fergusson DA
      • et al.
      Restrictive or liberal red-cell transfusion for cardiac surgery.
      • Murphy GJ
      • Pike K
      • Rogers CA
      • et al.
      Liberal or restrictive transfusion after cardiac surgery.
      • Shehata N
      • Whitlock R
      • Fergusson DA
      • et al.
      Transfusion requirements in cardiac surgery III (TRICS III): Study design of a randomized controlled trial.
      In the Transfusion Requirements in Cardiac Surgery-III (TRICS-III) trial, patients were transfused with RBC when hemoglobin was <7.5 g dL−1 in the restrictive group or when hemoglobin fell below 9.5 g dL−1 in the intensive care unit and below 8.5 g dL−1 on the ward in the liberal group.
      • Mazer CD
      • Whitlock RP
      • Fergusson DA
      • et al.
      Restrictive or liberal red-cell transfusion for cardiac surgery.
      ,
      • Shehata N
      • Whitlock R
      • Fergusson DA
      • et al.
      Transfusion requirements in cardiac surgery III (TRICS III): Study design of a randomized controlled trial.
      In the Transfusion Indication Threshold Reduction (TITRe-2) trial, RBCs were transfused with a hemoglobin level of <7.5 and <9.5 g dL−1 after on-pump cardiac surgery in the restrictive and the liberal group, respectively.
      • Murphy GJ
      • Pike K
      • Rogers CA
      • et al.
      Liberal or restrictive transfusion after cardiac surgery.
      Both studies found no differences in mortality and major morbidity after 30 days between the 2 groups. However, the TITRe-2 study reported favorable survival after 90 days with the liberal transfusion strategy. In contrast, TRICS-III found no differences between the 2 groups after 6 months.
      • Mazer CD
      • Whitlock RP
      • Fergusson DA
      • et al.
      Six-month outcomes after restrictive or liberal transfusion for cardiac surgery.
      Furthermore, younger patients seemed to have a better survival rate with liberal transfusion in both studies. When compared with the present study by Helwani et al.,

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      the lowest hemoglobin values were relevantly lower in the acute bleeding group as compared to the restrictive groups in TRICS-III and TITRe-2. We might not exactly know the lowest hemoglobin values in the Helwani study, as measurement frequencies might have been reduced for blood-sparing reasons or due to missing consequences of very low hemoglobin values. Unfortunately, Helwani, et al. could not provide data on end-organ ischemia such as, for example, increased lactate values or low near-infrared spectroscopy values in the acute bleeding group.

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      ,
      • Bolliger D
      • Erb JM
      • Buser A.
      Controversies in the clinical practice of patient blood management.
      Furthermore, the exact mechanism of anemia in the present study was not clear. Obviously, increased blood loss during and after surgery might be the most common etiology. However, massive hemodilution might also have contributed to low hemoglobin values but not necessarily to reduced RBC mass.
      What can perioperative physicians learn from this study? Jehovah's Witness patients have proved to be the ideal candidates for patient blood management (PBM)
      • Boer C
      • Meesters MI
      • Milojevic M
      • et al.
      2017 EACTS/EACTA guidelines on patient blood management for adult cardiac surgery.
      ,
      • Tibi P
      • McClure RS
      • Huang J
      • et al.
      STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management.
      without an option to transfuse. Patient blood management aims to avoid unnecessary RBC transfusion by multiple interventions, thereby eventually improving patient outcome.
      • Bolliger D
      • Erb JM
      • Buser A.
      Controversies in the clinical practice of patient blood management.
      A strict PBM protocol, as suggested by recent guidelines,
      • Boer C
      • Meesters MI
      • Milojevic M
      • et al.
      2017 EACTS/EACTA guidelines on patient blood management for adult cardiac surgery.
      ,
      • Tibi P
      • McClure RS
      • Huang J
      • et al.
      STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management.
      might allow for bloodless cardiac surgery even in patients at highest risk for bleeding.
      • Fassl J
      • Matt P
      • Eckstein F
      • et al.
      Transfusion of allogeneic blood products in proximal aortic surgery with hypothermic circulatory arrest: Effect of thromboelastometry-guided transfusion management.
      In JW patients, preoperative improvements of RBC mass and perioperative optimization of hemostasis seem to be most important. In a recent study including 137 JW patients undergoing different cardiac surgical procedures, successful hemoglobin optimization by adding iron/vitamins or erythropoietin to achieve a target hemoglobin >12 g dL−1 in combination with timely discontinuation of antiplatelet and anticoagulant agents were associated with fewer adverse events and lower mortality as compared to “nonoptimized” JW patients.
      • Tanaka A
      • Ota T
      • Uriel N
      • et al.
      Cardiovascular surgery in Jehovah's Witness patients: The role of preoperative optimization.
      Importantly, total RBC mass rather than absolute hemoglobin values might be more relevant.

      Tanaka KA, Alejo D, Ghoreishi M, et al. Impact of preoperative hematocrit, body mass index, and red cell mass on allogeneic blood product usage in adult cardiac surgical patients: Report From a statewide quality initiative [e-pub ahead of print]. J Cardiothorac Vasc Anesth 2023:37:214–220

      Different strategies have been recommended and studied. The administration of combined intravenous iron and erythropoiesis-stimulating agents (ESA) might be the most promising.

      Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery [e-pub ahead of print]. J Cardiothorac Vasc Anesth. 2023;37:266–275

      Different studies have shown that such a strategy could reduce the perioperative need for RBC transfusion in non-JW patients.

      Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery [e-pub ahead of print]. J Cardiothorac Vasc Anesth. 2023;37:266–275

      However, most studies could not show an effect on morbidity or mortality.

      Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery [e-pub ahead of print]. J Cardiothorac Vasc Anesth. 2023;37:266–275

      Finally, even with such elaborate strategies, increased hemoglobin values are not always achievable.
      • Bolliger D
      • Sreeram G
      • Duncan A
      • et al.
      Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.
      In the above-mentioned study, only 93 of 137 patients (68%) achieved a preoperative hemoglobin value >12 g dL−1 despite interventions to improve RBC mass.
      • Tanaka A
      • Ota T
      • Uriel N
      • et al.
      Cardiovascular surgery in Jehovah's Witness patients: The role of preoperative optimization.
      Limitations in the preoperative treatment time must also be kept in mind,

      Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery [e-pub ahead of print]. J Cardiothorac Vasc Anesth. 2023;37:266–275

      often leading to insufficient hemoglobin optimization. The worse outcome of patients with urgent surgery in the present study

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      might be, at least, partially explained by such facts. It remains unclear whether nonanemic JW patients should be treated with ESA and/or intravenous iron before cardiac surgery. Total RBC mass should be kept in mind,

      Tanaka KA, Alejo D, Ghoreishi M, et al. Impact of preoperative hematocrit, body mass index, and red cell mass on allogeneic blood product usage in adult cardiac surgical patients: Report From a statewide quality initiative [e-pub ahead of print]. J Cardiothorac Vasc Anesth 2023:37:214–220

      as well as potential side effects of intravenous iron and ESA.

      Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery [e-pub ahead of print]. J Cardiothorac Vasc Anesth. 2023;37:266–275

      However, given that most deaths in the present study might have been directly related to end-organ ischemia, means to increase RBC mass should potentially be considered also in nonanemic JW patients, especially in those undergoing complex cardiac surgery.
      Of note, recent advances in PBM, such as coagulation management guided by viscoelastic testing,
      • Boer C
      • Meesters MI
      • Milojevic M
      • et al.
      2017 EACTS/EACTA guidelines on patient blood management for adult cardiac surgery.
      • Tibi P
      • McClure RS
      • Huang J
      • et al.
      STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management.
      • Fassl J
      • Matt P
      • Eckstein F
      • et al.
      Transfusion of allogeneic blood products in proximal aortic surgery with hypothermic circulatory arrest: Effect of thromboelastometry-guided transfusion management.
      might not have been available or common in the early phase of the Helwani et al. study.

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      Again, it would be interesting to know whether patient outcome has improved over the years. However, such an analysis might be limited by the low number of included patients in the Helwani et al. study.

      Helwani MA, De Wet CJ, Pennington B, et al. Severe acute blood loss anemia in Jehovah's Witnesses undergoing cardiac surgery: Single academic center experience [e-pub ahead of print]. J Cardiothorac Vasc Anesth. !!! WILL BE PUBLISHED IN THE SAME ISSUE OF JCVA AS THIS EDITORIAL !!!!

      In summary, many JW patients can undergo major surgery by implementing a strict PBM protocol without an option to transfuse, but they may be at an increased risk of death in the case of extensive bleeding after complex cardiac surgery. Preoperative optimization of RBC mass, intraoperative blood conservation, and meticulous hemostasis techniques are crucial. Over the years, different treatment options, such as ESA or factor concentrates, have become available, and are acceptable for many JW patients. The use of hemoglobin-based oxygen carriers as treatment options in JW patients has recently been described,
      • 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.
      but its availability is severely limited. In the future, additional treatments, such as platelet substitutes, might become optional for JW patients.
      • Tan SJ
      • Nakahara K
      • Sou K
      • et al.
      An Assay to Evaluate the Function of Liposomal Platelet Substitutes Delivered to Platelet Aggregates.
      Lastly, a minimally invasive cardiovascular surgical approach holds promise in lowering transfusion risk,
      • Costa F
      • Cohen MG.
      Transfusion and Mortality After Transcatheter Aortic Valve Replacement: Association or Causation?.
      but PBM remains the guiding principle in optimizing overall clinical outcome.

      Conflict of Interest

      None.

      Acknowledgments

      The authors thank Allison Dwileski, MSc, Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Switzerland, for editorial assistance.

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