A 55-year-old African American male construction worker sought treatment from the emergency department with a 3-week history of melena and heart palpitations as well as a 2-week history of weakness and shortness of breath. His melena had stopped 2 days before admission. In addition, he experienced two syncopal episodes, one of which resulted in a fall. His vital signs on arrival included temperature 99.4°F, heart rate 121 bpm, blood pressure 148/55, and respiratory rate of 26 with SpO2 98% on room air. Physical examination was remarkable for tachycardia and pale sclera. Initial laboratory values on arrival included hemoglobin (Hb), 3.2 g/dL (reference range, 13.7–17.5 g/dL); hematocrit (HCT), 10.3% (reference range, 40%-51%); WBC, 18.9 × 103/μL (reference range, 3.7–10.3 × 103/μL); and platelet count, 211 × 103/μL (reference range, 155–369 × 103/μL) with an unremarkable basic metabolic panel. Lactate was elevated at 2.9 (reference range, 0.5–2.2 mmol/L), and iron studies showed a low ferritin of 19 (reference range, 30–400 ng/mL), a serum iron of 12 (reference range, 50–170 μg/dL), and a transferrin saturation of 4% (reference range, 14%-50%). Phlebotomies for laboratory tests were minimized to conserve RBCs in the patient.
Review of systems revealed chronic generalized muscle pain from physical labor for which he frequently took ibuprofen. Medical history was unremarkable; specifically, he had no history of a bleeding disorder, sickle cell anemia, or any malignancy. Family history was also noncontributory, including no history of a bleeding disorder. His social history, however, was particularly relevant for being a practicing Jehovah's Witness, and he confirmed he would not accept human blood products.
He was started on darbepoetin 100 μg (once daily subcutaneously), iron sucrose complex 100 mg (once daily intravenously, for 10 days), vitamin B12, and folic acid in an attempt to raise his hemoglobin. He was also placed on nasal oxygen.
Clinical workup was initiated to look for signs of active bleeding, including a computed tomography scan of the abdomen and an upper gastrointestinal endoscopy, which were both negative. Of concern, the next morning, his laboratory values revealed a drop in Hb to 2.9 g/dL and HCT to 10.3%.
At this point, the clinical team asked, "What can we do for this patient?" He had a dangerously low Hb and his lactate was elevated, so his tissues were theoretically not getting enough oxygen because of his severe anemia. However, he would not accept any blood transfusions (which would increase his oxygen-carrying capacity). The question became: Are there ways we can circulate more oxygen to his vital organs without using human blood products?
Members of our Jehovah's Witness community suggested that we investigate the use of Sanguinate, a bovine-derived artificial oxygen carrier, available through the US Food and Drug Administration (FDA) Expanded Access Program. Both the Prolong Pharmaceutical Company that produces Sanguinate and our institutional review board approved this patient for phase I experimental use of this product to act as a therapeutic bridge until his bone marrow was able to increase his peripheral RBC counts. As a result of the quick collaborative work by our blood bank director and the pharmaceutical company, the product arrived within 24 hours ready for use. He received two doses of Sanguinate on admission day 5, but he refused further doses because he subjectively felt so much better. Sanguinate is supplied in 500-mL single-use bags at a concentration of 40 mg/mL. The product is received from the manufacturer free of charge, ready for patient use, and with no preparation/reconstitution required. It is to be stored at 2°C to 8°C. The team was instructed to give the product by a steady state 2-hour infusion every 6 hours for the first day. From being bedridden because of weakness, he was able to sit up at the edge of the bed shortly after the first unit and was able to ambulate with minimal assistance the next morning several hours after completing the second unit. Importantly, the next morning, his Hb was noted to be 3.7 g/dL (from 2.9 g/dL 2 days prior) and lactate was noted to be 0.7 mmol/L (from 2.9 mmol/L on admission). Four days after the Sanguinate infusion, his Hb increased to 5.1 g/dL Figure 1. He was discharged on hospital day 15 with a Hb of 6.6 and without complications or adverse reactions to the product. The patient's melena and anemia were ultimately attributed to his frequent ibuprofen use causing stomach ulcers complicated by an acute on chronic gastrointestinal bleed. Of note, after administration of Sanguinate, his serum demonstrated a red discoloration, as seen in Image 1, which is important for laboratory professionals to be aware of, as it can affect colorimetric laboratory tests. This color change was as expected per the manufacturer's representative, and it has the same effects as a hemolyzed sample would on these tests. It is important for the laboratory to communicate this with clinicians, so they can make informed decisions on ordering further laboratory tests. Importantly, hematology testing will not be affected; therefore, hemoglobin and hematocrit can still be accurately followed in these patients.
Trend graph of patient's hemoglobin and hematocrit. Sanguinate was administered on hospital day 4.
Am J Clin Pathol. 2020;153(3):287-293. © 2020 American Society for Clinical Pathology