Abstract: Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage, enhancing the survivability of platelets during storage or transfusion and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage. In addition, the modified annexin prevents lipid loss from platelets during storage.

Abstract: Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage.

Abstract: Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage, enhancing the survivability of platelets during storage or transfusion and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothrombinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage. In addition, the modified annexin prevents lipid loss from platelets during storage.

Abstract: Modified annexin proteins, including heterodimers and homodimer of various human annexins, are provided for treatment of cerebral thrombosis and global cerebral ischemia. Also provided are phosphatidylserine (PS) binding proteins for treatment of cerebral thrombosis and global cerebral ischemia. The modified annexins and/or PS binding proteins bind PS on cell surfaces, thereby preventing the attachment of leukocytes and platelets to endothelial cells during post-ischemic reperfusion. By maintaining endothelial cell and vascular wall integrity PS binding proteins and/or modified annexin proteins decrease cerebral hemorrhage. Modified annexins and other PS binding proteins also suppress the production of mediators of edema, the extension of cerebral damage during reperfusion and the risk of rethrombosis. Thus, modified annexin proteins and/or other PS binding proteins decrease brain damage following cerebral thrombosis and global cerebral ischemia.

Abstract: A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

Abstract: Compositions for and methods of attenuating and/or preventing ischemia-reperfusion injury (IRI) are provided. One method comprises administering to a patient in need thereof an agent that binds phosphatidylserine (PS) located on cell surfaces, i.e., PS binding agent. Another method comprises administering to an organ transplant recipient a therapeutic composition comprising a PS binding agent. A method of preventing IRI to cells is also provided. The method comprises adding a PS-binding agent to a therapeutic composition used to treat the cells. Further provided is a method of protecting an organ or a tissue susceptible to IRI. The method comprises contacting the organ or tissue with a PS-binding agent. Such an agent may, for example, attenuate IRI in patients with stroke or myocardial infarction, or following surgical operations. PS-binding agents include modified annexin proteins, antibodies against PS molecules, and other anti-PS molecules.

Abstract: Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage.