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Sophie Lanzkron - One of the best experts on this subject based on the ideXlab platform.
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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
Blood, 2014Co-Authors: Candice M Nalley, Abe Abuchowski, Steven Hsu, Sophie LanzkronAbstract: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. Disclosures Off Label Use: Pegylated Carboxyhemoglobin Bovine was used to improve oxygen delivery. Abuchowski:Prolong Pharmaceuticals: Employment. Lanzkron:NHLBI: Research Funding.
Neil E I Langlois - One of the best experts on this subject based on the ideXlab platform.
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Investigation into the potential for post-mortem formation of Carboxyhemoglobin in bodies retrieved from fires
Forensic Science Medicine and Pathology, 2018Co-Authors: Claire J. Sully, G. Stewart Walker, Neil E I LangloisAbstract:The forensic investigation of a deceased person retrieved following a fire includes measuring Carboxyhemoglobin. A Carboxyhemoglobin saturation above 10% is considered indicative of respiration during a fire, implying the person had been alive. This relies on the assumption that carbon monoxide will not diffuse into blood used for toxicological analysis. This project investigated the potential for carbon monoxide to passively diffuse into a body and if Carboxyhemoglobin levels could become elevated post-mortem. Stillborn piglets with intact skin were exposed to carbon monoxide. Carboxyhemoglobin formed in the hypostasis of the skin, but Carboxyhemoglobin levels in blood from the heart and chest cavities were not significantly elevated. However, defects in the skin over body cavities (producing breaches to replicate cases with stab wounds or heat damage) resulted in cavity blood Carboxyhemoglobin levels above 10%. A review of fire death cases in South Australia 2000-2015 was performed to determine the origin of the blood samples used for toxicological analysis and the incidence of cases with breaches of body cavities. This revealed a small number of cases in which blood from the cavities had been analyzed when cavity breaches were present. Thus, there is a potential for significant elevation of Carboxyhemoglobin saturation post-mortem in forensic casework involving bodies retrieved from fires.
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Review of autopsy reports of deaths relating to fire in South Australia 2000–2015
Forensic Science Medicine and Pathology, 2018Co-Authors: Claire J. Sully, G. Stewart Walker, Neil E I LangloisAbstract:It has been noted there are gaps and inconsistencies in data pertaining to fire related deaths in Australia, which poses difficulties for analysis of national statistics. A search of post-mortem examination reports at Forensic Science SA from 2000 to 2015 revealed 275 cases regarded as fire related in which the body had been involved in a fire. The autopsy reports were evaluated to determine parameters including the location of the fire event, age and sex of victim, as well as the presence of soot in the airways and cherry-red coloration to the blood and/or organs, in addtion to toxicological levels of Carboxyhemoglobin and alcohol. Fire events were clasified as structural, transportation or open air in type. Males were more commonly victims than females, especially in transportation fires, where males aged below 50 years were most at risk of death. Carboxyhemoglobin levels tended to be lower in victims of transportation fires. This study has confirmed that presence of soot in the respiratory tract and cherry-red coloration of a body retrieved from a fire are both linked to an increased level of blood Carboxyhemoglobin. These findings significantly contribute to the documentation of fire deaths in Australia.
Candice M Nalley - One of the best experts on this subject based on the ideXlab platform.
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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
Blood, 2014Co-Authors: Candice M Nalley, Abe Abuchowski, Steven Hsu, Sophie LanzkronAbstract: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. Disclosures Off Label Use: Pegylated Carboxyhemoglobin Bovine was used to improve oxygen delivery. Abuchowski:Prolong Pharmaceuticals: Employment. Lanzkron:NHLBI: Research Funding.
Claire J. Sully - One of the best experts on this subject based on the ideXlab platform.
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Investigation into the potential for post-mortem formation of Carboxyhemoglobin in bodies retrieved from fires
Forensic Science Medicine and Pathology, 2018Co-Authors: Claire J. Sully, G. Stewart Walker, Neil E I LangloisAbstract:The forensic investigation of a deceased person retrieved following a fire includes measuring Carboxyhemoglobin. A Carboxyhemoglobin saturation above 10% is considered indicative of respiration during a fire, implying the person had been alive. This relies on the assumption that carbon monoxide will not diffuse into blood used for toxicological analysis. This project investigated the potential for carbon monoxide to passively diffuse into a body and if Carboxyhemoglobin levels could become elevated post-mortem. Stillborn piglets with intact skin were exposed to carbon monoxide. Carboxyhemoglobin formed in the hypostasis of the skin, but Carboxyhemoglobin levels in blood from the heart and chest cavities were not significantly elevated. However, defects in the skin over body cavities (producing breaches to replicate cases with stab wounds or heat damage) resulted in cavity blood Carboxyhemoglobin levels above 10%. A review of fire death cases in South Australia 2000-2015 was performed to determine the origin of the blood samples used for toxicological analysis and the incidence of cases with breaches of body cavities. This revealed a small number of cases in which blood from the cavities had been analyzed when cavity breaches were present. Thus, there is a potential for significant elevation of Carboxyhemoglobin saturation post-mortem in forensic casework involving bodies retrieved from fires.
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Review of autopsy reports of deaths relating to fire in South Australia 2000–2015
Forensic Science Medicine and Pathology, 2018Co-Authors: Claire J. Sully, G. Stewart Walker, Neil E I LangloisAbstract:It has been noted there are gaps and inconsistencies in data pertaining to fire related deaths in Australia, which poses difficulties for analysis of national statistics. A search of post-mortem examination reports at Forensic Science SA from 2000 to 2015 revealed 275 cases regarded as fire related in which the body had been involved in a fire. The autopsy reports were evaluated to determine parameters including the location of the fire event, age and sex of victim, as well as the presence of soot in the airways and cherry-red coloration to the blood and/or organs, in addtion to toxicological levels of Carboxyhemoglobin and alcohol. Fire events were clasified as structural, transportation or open air in type. Males were more commonly victims than females, especially in transportation fires, where males aged below 50 years were most at risk of death. Carboxyhemoglobin levels tended to be lower in victims of transportation fires. This study has confirmed that presence of soot in the respiratory tract and cherry-red coloration of a body retrieved from a fire are both linked to an increased level of blood Carboxyhemoglobin. These findings significantly contribute to the documentation of fire deaths in Australia.
Steven Hsu - One of the best experts on this subject based on the ideXlab platform.
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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
Blood, 2014Co-Authors: Candice M Nalley, Abe Abuchowski, Steven Hsu, Sophie LanzkronAbstract: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. Disclosures Off Label Use: Pegylated Carboxyhemoglobin Bovine was used to improve oxygen delivery. Abuchowski:Prolong Pharmaceuticals: Employment. Lanzkron:NHLBI: Research Funding.