Use of a Hemoglobin Substitute (HBOC-201) to Treat Acute Anemia in a Leukemic Patient with Anti-Vel Antibodies

Background

The Vel-negative blood type is a rare autosomal recessive trait, occurring in 1 in 4000 persons. It is extremely difficult to supply blood to patients with anti-Vel antibodies, and the situation is even more challenging for Vel-negative patients with leukemia who may have high transfusion needs. There are case reports of treatment with hemoglobin substitutes in Jehovah's Witnesses and surgical patients. To the best of our knowledge, we report the first use of a hemoglobin substitute, HBOC-1201 (HemoPure) to treat a patient with refractory acute myeloid leukemia (AML) and anti-Vel antibodies.

Case Report

Our patient is a 67-year-old Caucasian man with a one-year history of acute myeloid leukemia, refractory to multiple hypomethylator- and chemotherapy-based regimens. History is also significant for coronary artery disease with type 2 NSTEMI due to severe anemia. He has experienced prolonged pancytopenia due to leukemia and chemotherapy and required blood transfusions approximately weekly. Anti-Vel antibodies make transfusion of compatible blood challenging, and we utilized a hemoglobin transfusion threshold of 5 g/dL. Working with the American Red Cross and the American Rare Donor Program (ARDP), we transfused 44 units of Vel-negative blood over a one-year period, depleting the available Vel-negative units in North America. He presented to the hospital with productive cough and dyspnea. Initial labs revealed acute on chronic anemia with hemoglobin 3.5 g/dL. CT of the chest revealed right lower lobe pneumonia. Given critical anemia in the setting of pneumonia and possible sepsis, the patient needed immediate blood transfusion. Compatible Vel-negative blood was not available in North America. While awaiting availability of international blood units through the Red Cross and ARDP, we considered the choices of 1) transfusing incompatible blood or 2) administering a blood substitute. Because individuals with anti-Vel antibodies may develop severe acute hemolytic transfusion reactions when transfused incompatible blood, we chose to treat with HBOC-1201 (Biopure Corporation, Cambridge, MA), a bovine hemoglobin polymer that lacks a red blood cell membrane and thus red cell antigens such as Vel. We obtained an emergency IND from the FDA and local IRB approval. Three 32-gram units of HBOC-1201 were successfully transfused, with hemoglobin rise from 3.5 to 4.5 g/dL. Common adverse effects associated with the use of acellular hemoglobin substitutes include increase in concentration of methemoglobin and vasopressor effects leading to elevated blood pressure, fluid overload, and myocardial infarction. Our patient was monitored closely and tolerated the transfusion without any apparent adverse events.

Conclusion

During a challenging clinical situation, we successfully treated severe acute anemia in a patient with refractory AML and anti-Vel antibodies, using the acellular bovine hemoglobin-based blood substitute HBOC-1201, when compatible blood was not available. The infusion was tolerated without complications. Hemoglobin substitutes may be considered as bridging treatments in critically anemic patients such as those with hematologic malignancies when red blood cell transfusion is not an option.