raffinose and Anemia

To describe the successful treatment of acute, life-threatening anemia with the oxygen therapeutic agent, hemoglobin (Hb) raffimer.. A 53-yr-old female Jehovah's Witness developed severe anemia following total hip replacement. Due to prior patient directive, red blood cells were not transfused. Tachycardia, hypotension, electrocardiographic abnormalities and mental status changes developed with a nadir Hb concentration of 3.2 g x dL(-1). Hb raffimer is a purified, cross-linked, human Hb solution developed as a substitute for red blood cell Hb. After obtaining informed consent as well as Food and Drug Administration and Institutional Review Board approval for compassionate use, 2 L of Hb raffimer (Hemolink, Hemosol, Inc., Toronto, ON, Canada) were administered along with ferrous sulfate and epoetin alfa therapy. The patient's Hb level rose to 5.5 g x dL(-1) with resolution of symptoms. To allow recovery of red blood cell mass while maintaining Hb level > 4.5 g x dL(-1), additional 1000 mL doses of Hb raffimer were administered on postoperative days three, five and seven (total dose = 500 g Hb). The patient developed no serious adverse events related to treatment with Hb raffimer. By postoperative day 14, the patient's Hb level increased to 6.5 g x dL(-1) with a hematocrit of 23%. The patient was discharged.. Use of Hb raffimer as a bridge to recovery of this patient's red blood cell mass may have prevented adverse clinical outcome. Because this product is a purified Hb solution devoid of other cellular components, it may be accepted as therapy by patients who, due to religious conviction, refuse allogeneic red blood cell transfusion.

Topics: Anemia; Erythrocyte Transfusion; Female; Hemoglobins; Humans; Jehovah's Witnesses; Middle Aged; Postoperative Complications; Raffinose

Hemoglobin-based oxygen carriers hold promise for the treatment of acute anemia.. We report a patient with severe dysfunctional uterine bleeding. During her hospitalization, her lowest hemoglobin level was 3.1 g/dL, with a hematocrit of 9.3%. An investigational product, o-raffinose cross-linked human hemoglobin solution (hemoglobin raffimer), was infused along with ongoing high-dose recombinant human erythropoietin and estrogen. The time until the patient's own hematopoiesis provided sufficient red blood cell mass was successfully managed by reducing oxygen demand and providing multiple hemoglobin-based oxygen carrier infusions. After hemoglobin-based oxygen carrier administration, transient pulmonary hypertension and fever were noted. She was discharged after corrective surgery 7 days after hemoglobin-based oxygen carrier administration with a hemoglobin level of 7.8 g/dL.. The hemoglobin level-based oxygen carrier improved oxygen delivery and permitted uterine corrective surgery.

Topics: Adult; Anemia; Emergencies; Female; Hematocrit; Hemoglobins; Humans; Hypertension, Pulmonary; Jehovah's Witnesses; Menorrhagia; Raffinose

Topics: Anemia; Clinical Trials, Phase II as Topic; Drug Approval; Drug Industry; Hemoglobins; Humans; Raffinose; Single-Blind Method; United States; United States Food and Drug Administration

Several different preparations of cross-linked hemoglobin (CLHb) are being evaluated for their efficacy and safety as red cell substitutes in a variety of preclinical and clinical settings. Because CLHb is known to sequester nitric oxide (NO) and inhibit NO-mediated processes, we hypothesized that CLHb would have a hemostatic effect by enhancing platelet reactivity, inducing vasoconstriction, or both. Infusion of o-raffinose CLHb shortened the prolonged microvascular bleeding time and decreased blood loss from ear incisions in rabbits rendered anemic and thrombocytopenic. Moreover, this hemostatic effect persisted for at least 24 hours after infusion. Phenylephrine induced a degree of vasoconstriction similar to that induced by CLHb but did not shorten the bleeding time or decrease blood loss, suggesting that vasoconstriction alone cannot account for the hemostatic effect of CLHb. There was no evidence of CLHb-induced activation of coagulation in vivo, since infusion of CLHb did not increase circulating levels of thrombin-antithrombin complex. In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets. This potentiating effect was not attenuated by the addition of superoxide dismutase or catalase. To evaluate the potential arterial thrombogenicity of CLHb, a model of carotid artery thrombosis was developed in rabbits without thrombocytopenia or anemia. Compared with albumin infusion, CLHb infusion shortened the time to complete carotid occlusion. These data suggest that CLHb may shift the thromboregulatory balance toward clot formation, resulting in decreased bleeding in anemic and thrombocytopenic rabbits and possibly increasing arterial thrombogenicity in normal rabbits.

Topics: Adrenergic alpha-Agonists; Anemia; Animals; Antithrombin III; Bleeding Time; Carotid Artery Thrombosis; Cross-Linking Reagents; Disease Models, Animal; Dose-Response Relationship, Drug; Hemoglobins; Hemorrhage; Hemostasis; Kinetics; Male; Microcirculation; Peptide Hydrolases; Phenylephrine; Platelet Aggregation; Rabbits; Raffinose; Rats; Rats, Sprague-Dawley; Serum Albumin; Thrombocytopenia; Vasoconstriction

Severe anemia is a major cause of death in falciparum malaria. Blood transfusion increases survival in humans and in animal models of this disease. Because of logistic constraints and viral contamination of the blood supply, transfusions are frequently not practical in endemic regions. Modified hemoglobin is an effective O2 carrier in hemorrhagic shock. It is free of infectious contamination, may not require refrigeration, and because of its nitric oxide scavenging and small size, may have pharmacologic benefits in malaria. The effects of transfusions of modified hemoglobin in rats with high-grade parasitemia were evaluated. Modified hemoglobin decreased lactic acidosis and corrected anemia as well as transfusions with red blood cells; these findings may correlate with improved survival and suggest a possible proerythropoietic effect. Further study of this novel therapy is warranted.

Topics: Acidosis, Lactic; Anemia; Animals; Blood Component Transfusion; Female; Hemoglobins; Malaria, Falciparum; Raffinose; Rats; Rats, Inbred Lew; Treatment Outcome