A 26-year-old male presented to his primary care physician with back pain of several weeks' duration. His past medical history was pertinent only for gastroesophageal reflux. The physician diagnosed a herniated lumbar disk and prescribed epidural injections, along with naproxen for the pain. The symptoms seemed to improve, but approximately 2 weeks after his initial presentation, the patient began to experience progressive weakness, dizziness, dyspnea on exertion, malaise, and palpitations. When his symptoms suddenly worsened while he was out of town on a business trip, he presented to a local emergency department (ED). Evaluation in the ED revealed that he was severely anemic, with a hemoglobin (Hgb) level of 2.6 g/dL. (Additional laboratory results are shown in Table 1.) The patient denied melena, hematochezia, hematemesis, or any other symptoms suggestive of blood loss. An ECG revealed sinus tachycardia. A chest radiograph was normal. While being evaluated, the patient reported that he was a Jehovah's Witness and would refuse all major blood products. After receiving epoetin alfa 40,000 units SC and iron sucrose 200 mg IV, he was transferred to our institution, which has an established Blood Conservation Program with experience in the treatment of patients who cannot receive certain blood products.
Assessment On arrival at our facility, the patient was admitted directly to the medical ICU for further evaluation and anemia management. Vital signs on admission were as follows: temperature, 98°F; BP, 130/70 mm Hg; respiration rate, 16 breaths per minute; pulse, 110 beats per minute; and oxygen saturation, 100% on room air. He arrived awake, alert, oriented, and in no acute distress. His mucous membranes were dry, and he was noted to have conjunctival pallor. Skin was warm with no evidence of petechiae, purpura, or rash. Findings on respiratory, cardiac, abdominal, and neurologic examination were unremarkable.
A discussion was held with the patient and his family to determine which major and minor blood fractions he would accept or refuse. After his decisions were documented on the Saint Luke's Hospital Blood Products and Procedures Directive (Figure 1) and communicated to the medical team, a plan for care was developed.
The care plan The patient was started on IV fluid resuscitation to maintain circulatory support. Continuous, supplemental oxygen at 2 L/min was used to maximize oxygen delivery. Conservative phlebotomy measures were initiated to minimize blood loss. All laboratory specimens were drawn using either microtainers or 2-mL pediatric tubes depending on the type of study ordered and its requirements. Laboratory draws were restricted; no daily laboratory draws were allowed. The gastroenterology and hematology services were consulted to help determine the etiology of the anemia.
Extensive workup The extensive workup began with evaluation for an occult GI bleed. Esophagogastroduodenoscopy revealed mild antral gastritis, and the gastric biopsy was positive for mild, superficial gastritis. Findings on colonoscopy, celiac screen, and assessment for Meckel diverticulum were negative. Serology for Helicobacter pylori was positive for antibody, but as the gastric biopsy showed no evidence of Hpylori, treatment was not initiated. CT enterography revealed borderline splenomegaly and borderline enlarged mesenteric lymph nodes but no obvious source of blood loss. There was no evidence of hemolytic anemia, as lactate dehydrogenase and haptoglobin levels were normal. The bone marrow biopsy showed erythroid hyperplasia, essentially a normal finding in light of the patient's severe iron deficiency anemia. Marrow results were negative for non-Hodgkin lymphoma, myelofibrosis, and neoplasm. The patient did not have paroxysmal nocturnal hemoglobinuria. Although suspicion for myeloproliferative disease was low, evaluation for a Janus kinase 2 (JAK2) mutation was performed because of the patient's presenting symptoms and otherwise negative workup. No evidence of a JAK2 mutation was found.
The treatment plan Therapy for the iron deficiency included iron sucrose 200 mg IV on hospital days 1 through 5, and iron sucrose 300 mg IV on hospital day 8. To stimulate erythropoiesis, epoetin alfa 35 IU/kg was given SC, which equated to 4,000 units daily on hospital days 1 through 3 and on day 7. Although the patient's vitamin B12 and folate levels were normal, he was given one dose of vitamin B12 1,000 mcg IM on day 10 to support increased erythropoiesis. On day 7, the patient was started on ferrous sulfate 325 mg twice daily, prenatal vitamin, and vitamin C 500 mg twice daily. A proton pump inhibitor was given twice daily throughout his hospitalization. A summary of therapy administered during the patient's hospital stay is presented in Table 2.
Outcome During the course of his 10-day hospitalization, the patient's Hgb level rose from 2.6 g/dL to 5.8 g/dL. His hematocrit increased from 11% to 22%. No blood transfusions were given. The patient remained hemodynamically stable. There was no evidence of bleeding and no identifiable cause for his profound anemia. He did complain of dyspnea with minimal exertion but was able to participate in physical therapy, and his functional status improved daily. He was discharged home on a daily prenatal vitamin, ferrous sulfate 325 mg twice daily, and vitamin C 500 mg twice daily and instructed to follow up with his primary care physician and hematologist in 1 week. Six days after discharge, his Hgb level had increased to 7.8 g/dL. One year later, his Hgb level was 14.9 g/dL.
- Severe anemia in a patient who will not accept blood products presents a significant challenge for the health care team. As health care providers, we must be aware of these patients' wishes and have plans in place to provide care from the time of admission to the day of discharge.
- Jehovah's Witnesses will refuse all major blood fractions, including whole blood, packed RBCs, plasma, and platelets. Minor fractions are allowed and the decision to accept or refuse these fractions is a personal one made by each Witness.
- The goals of anemia management include cessation of blood loss, meticulous conservation of blood, optimizing hematopoiesis, and assessing the patient's physiologic tolerance of anemia.
- Profound anemia with a hemoglobin level of 2.6 g/dL is survivable without a blood transfusion.
- A conservative dosing regimen of erythropoiesis-stimulating agents can be effective in increasing the hemoglobin level of severely anemic patients.
The Jehovah's Witness community has grown in numbers, with an estimated 7 million members worldwide.1 Based on their interpretation of biblical passages, Witnesses view “life as God's gift represented by blood.”2 Any acceptance of blood could compromise a Witness' spiritual being and hope for eternal life; therefore, all major blood products are refused. Honoring these beliefs can be a challenging task for the medical team, particularly in a patient with severe anemia.
The early identification and documentation of transfusion preferences is the single most important step when providing medical care for a Jehovah's Witness. The transfusion of major fractions, including whole blood, packed RBCs, plasma, and platelets is prohibited; however, the transfusion of minor fractions is allowed, and the decision to accept or refuse is a personal one made by each Witness. A detailed explanation of each blood product should be provided to the patient and family, as the origin and recombinant technology of each product affects a Witness' decision to accept or refuse.3 For example, epoetin alfa is a commonly used agent to stimulate erythropoiesis. This medication contains albumin, which is considered to be a minor fraction.
Once the transfusion preferences have been determined, a treatment plan can be developed. The goals of anemia management include cessation of blood loss, meticulous conservation of blood, optimizing hematopoiesis, and assessing the patient's physiologic tolerance of anemia.4 When a patient presents with severe anemia, one must first rule out active bleeding. Once this has been addressed and corrected if present, efforts should be directed toward conservative phlebotomy measures to minimize blood loss. The next step is to stimulate erythropoiesis through the use of recombinant human erythropoietin, iron, vitamin B12, and folate.
Erythropoietin is a glycoprotein produced by the kidneys. It stimulates the production and differentiation of erythroid progenitors in the bone marrow. Epoetin alfa has the same biological effects as endogenous erythropoietin and is manufactured through recombinant DNA technology. Very few randomized controlled trials have been conducted on the use of this agent except in chronic renal disease patients. Nevertheless, use of epoetin alfa should be considered in severely anemic Jehovah's Witnesses. Several case reports have been published on the use of erythropoiesis-stimulating agents in this patient population.5 Although the dosing regimens and routes of administration varied, the end result was that these agents proved to be effective in the treatment of anemia. Currently, there is no single dosing recommendation for the use of epoetin alfa in severely anemic Jehovah's Witnesses.5 Significant risks are associated with the use of epoetin alfa, and it should be administered judiciously. In controlled trials, it has been shown to increase the risk of MI, stroke, venous thromboembolism, tumor progression or recurrence, and death.6 These risks are increased when the target Hgb level is greater than 11 g/dL.6 A conservative epoetin alfa dosing regimen was used in the case presented here, as the patient was hemodynamically stable and tolerating his anemia without evidence of an active bleed.
In otherwise healthy individuals at rest, an Hgb level of 5 g/dL has been well-tolerated without evidence of inadequate systemic oxygenation.7 Survival has been documented with Hgb values ranging from 3 to 5 g/dL and as low as 1 g/dL.8–10 The ability to tolerate anemia varies, depending on the patient's clinical situation and medical comorbidities. The case presented here illustrates a hemodynamically stable Jehovah's Witness with profound anemia; an unstable patient would require additional aggressive interventions. To minimize oxygen consumption and maximize oxygen delivery, consideration should be given to sedation, mechanical ventilation, neuromuscular blockade, and vasopressor support.3 In the event of an active bleed, local hemostatics, prohemostatics, and prothrombin complex concentrate (if allowed) to correct coagulation defects may be used.1 RBC substitutes have been administered to Jehovah's Witnesses with severe anemia on a compassionate use basis but are not currently approved by the FDA.11 The ultimate driving factor behind a treatment plan should be the patient's physiologic response to the anemia, as opposed to a numeric laboratory value only.
The Jehovah's Witness community continues to grow, and the practicing PA needs to be aware of the group's religious beliefs regarding blood products. The early identification of transfusion preferences is critical to the management of severe anemia in this population. Several blood-conserving techniques and pharmacologic agents can be used to treat severe anemia in Jehovah's Witnesses. When these methods are used, survival and recovery are possible without receiving allogeneic transfusions despite extremely low Hgb levels. JAAPA
The authors would like to thank Haseeb ahmed, DO, MHa; Colleen littrell, rN, BSN; Nikki Burk; and Jill King, RN, BSN, for their support and assistance with this manuscript.
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