Successful Use of Pegylated Carboxyhemoglobin Bovine As an Emergency Treatment for Severe Anemia in a Patient with Sickle Cell Disease and Hyperhemolysis: A Case Report

Introduction:

Modern biotechnology has long sought the development of a safe and effective red cell alternative. For patients with sickle cell disease and alloimmunization who develop severe anemia, few treatments exist to improve oxygen-carrying capacity. PEGylated carboxyhemoglobin bovine (PEG-Hb) may offer a novel treatment modality in such situations. Here we describe the use of the investigational drug PEG-Hb as an emergency treatment for severe anemia in a patient with sickle cell anemia (HbSS) who developed life-threatening hyperhemolysis following packed red blood cell transfusion.

Case Report:

A 28-year-old female with HbSS, not on hydroxyurea therapy, with complications including alloimmunization, multiple past episodes of acute chest syndrome, and avascular necrosis of the bilateral femoral heads, presented with severe pain in her back, legs, and hips, reported as the worst she had ever felt. Her urine was dark in color, and her hemoglobin dropped from 7 to 4.7 g/dL within 12 hours of presentation. She was diagnosed with acute hyperhemolysis following the transfusion of one unit of phenotypically matched red blood cells six days prior, with precipitated vaso-occlusive crisis. The patient received steroids and IVIG to mitigate the immune response, and erythropoietin or darbepoietin to stimulate erythropoiesis. It was felt that giving additional phenotypically matched red cells would lead to further hemolysis and bone marrow suppression. On hospital day 2, she developed a fever to 39.5 C and was tachycardic to 138 BPM. By hospital day 3, she was severely anemic with hemoglobin 3.5 g/dL, hematocrit 9.8%. On hospital day 5, she required 50% FiO2 to maintain her oxygen saturation above 95%. The patient’s absolute reticulocyte count dropped from 316k to 113.9k and nadired at 24.5K. Her ongoing hypoxemia, reticulocytopenia, and marked anemia were leading to severe tachycardia, fatigue, and depressed sensorium. To compensate for this severely symptomatic anemia, the investigational biologic PEGylated carboxyhemoglobin bovine (PEG-Hb) 40 mg/mL for intravenous infusion was requested from the manufacturer and granted under an emergency investigational new drug (IND) approval.

By hospital day 6, following two once-daily infusions (500 mL each = approximately 400 mg/kg/dose) of PEG-Hb, the patient reported feeling well with no pain and no shortness of breath. Anemia remained severe (hemoglobin 2.5 g/dL, hematocrit 10%). Additional investigational drug was requested, and the patient received six additional once-daily 500 mL infusions of PEG-Hb with continued improvement in exertional ability and tachycardia, though with mild dyspnea upon exertion. No adverse effects were noted with the infusions; there were no changes in renal function or episodes of hypertension. The patient was discharged home on day 32 with a hemoglobin of 4.1 g/dL.

Discussion:

Hemoglobin-based oxygen carriers have, in general, met problems including increased mortality and myocardial infarctions when compared with controls (Natanson C et al. JAMA. 2008;299(19):2304). This is postulated to be due to systemic vasoconstriction secondary to the nitric-oxide scavenging properties of cell-free hemoglobin (Buehler PW, et al. Transfusion. 2004;44(10):1516). In patients with sickle cell disease who already have elevated levels of circulating free heme (Uzunova W, et al. Biophys J. Sep 22, 2010; 99(6): 1976–1985), the potential additional free hemoglobin contributed by hemoglobin-based oxygen carriers may not confer a significant increase in risk. For patients with sickle cell disease and severe anemia for whom transfusion is not an option, PEG-Hb may present a viable alternative to transfusion.

This is the first reported case of the use of PEG-Hb in a patient with sickle cell disease and profound anemia from hyperhemolysis. This therapy is thought to have been lifesaving for this patient. Further research into the use of PEGylated carboxyhenoglobin bovine in patients with severe anemia secondary to sickle cell disease is warranted.