Disclosed are methods for treating bleeding disorders, such as hemophilia, in subjects in need thereof by administering an antibody that specifically binds CD73. The methods reduce production of adenosine, increase platelet activation and/or enhance the level of coagulation on the platelet surface to reduce and/or stop bleeding. In some embodiments, the methods can further include co-administering Factor VIII to treat the bleeding disorder.

Bayer HealthCare LLC

Methods for treating bleeding disorders

The present invention relates to novel methods of using blood substitutes to treat acute blood loss and novel pharmaceutical compositions comprising blood substitutes. Blood substitutes useful for the methods of the present invention can (1) induce expression of erythropoietin as tested in a cell culture under normoxic conditions, and/or (2) induce erythropoiesis under normoxic conditions as measured by (a) a decrease in the doubling time of the subject's hematocrit or hemoglobin, and/or (b) an increase in the subject's circulating erythropoietin level. Blood substitutes useful for the pharmaceutical compositions of the present invention can (1) stabilize HIF-1 alpha expression, and/or (2) down regulate NF-kappa B. Preferably, the blood substitutes are cross-linked hemoglobin blood substitutes, or more preferably, cross-linked hemoglobins that comprise a hemoglobin that is cross-linked intramolecularly with periodate-oxidized ATP, cross-linked intermolecularly with periodate-oxidized adenosine, and conugated with reduced glutathione.

Methods of treating acute blood loss

An improved blood substitute comprises purified hemoglobin, preferably bovine, cross-linked intramolecularly with periodate-oxidized ATP (o-ATP) and intermolecularly with periodate-oxidized adenosine (o-adenosine), combined with reduced glutathione (GSH), and optionally enriched with mannitol, non-electrolytes, and/or electrolytes. The blood substitute has prolonged intravascular persistence, can sustain plasma volume, has low oxygen affinity, can work as a physiological oxygen carrier, has vasodilator activity and can reduce the vasoconstriction that follows hemorrhage. A method of treating a human afflicted with acute blood loss and/or a sickling crisis of sickle cell anemia comprises intravenously administrating to the human an effective volume of the blood substitute.

Texas Tech University Health Sciences Center

Blood substitute

A method of prophylaxis or treatment of inflammatory conditions, including, but not limited to, intestinal epithelial inflammation due to intestine-specific conditions (e.g., Crohn's disease or ulcerative colitis) or systemic causes of inflammation (e.g., endotoxemia, sepsis, hemorrhagic shock/resuscitation or pancreatitis) is disclosed. In the method of the invention, an affected patient is administered a therapeutically effective amount of a composition including an NAD-related compound, in a form that is accessible to a receptor molecule, conveyed in a pharmaceutically acceptable carrier vehicle. NAD-related compounds include nicotinamide adenine dinucleotide (NAD.sup.+), cyclic adenosine diphosphate ribose (cADPR), or functionally equivalent analogues, derivatives, metabolites or agonists thereof or prodrugs therefor. Also disclosed are ex vivo and in vivo assay methods to test candidate compounds for activity, kits for carrying out the therapeutic methods or the assay methods of the invention and articles of manufacture that include compositions for use in the methods of the invention and instructions for the use thereof.

adenosine/hemorragia

Methods for treating bleeding disorders

Methods of treating acute blood loss

Blood substitute

Extracellular NAD.sup.+ and cADPR as potent anti-inflammatory agents

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