Abstract: The present invention relates to methods of treating sickle cell disease comprising reducing, in a subject in need of such treatment, the adherence between sickle RBCs and leukocytes. It is based, at least in part, on the discovery that leukocytes play a direct role in the initiation of venular occlusion. The present invention further provides for methods for identifying agents which decrease SS-RBC/leukocyte adherence and for animal models which may be used to further elucidate the mechanism of vaso-occlusion in sickle cell crises.

Abstract: Platelet-specific, chimeric immunoglobulin and immunoglobulin fragments are described. The chimeric molecules are made up of a nonhuman antigen binding region and a human constant region. Preferred immunoglobulins are specific for glycoprotein IIb/IIIa receptor in its complexed form; they block ligand binding to the receptor and prevent platelet aggregation. The immunoglobulins are useful in anti-thrombotic therapy when administered alone or in conjunction with thrombolytic agents, as well as in thrombus imaging.

Abstract: Platelet-specific, chimeric immunoglobulin and immunoglobulin fragments are described. The chimeric molecules are made up of a nonhuman antigen binding region and a human constant region. Preferred immunoglobulins are specific for glycoprotein IIb/IIIa receptor in its complexed form; they block ligand binding to the receptor and prevent platelet aggregation. The immunoglobulins are useful in anti-thrombotic therapy when administered alone or in conjunction with thrombolytic agents, as well as in thrombus imaging.

Abstract: The present invention is an assay for determining glycoprotein IIb/IIIa receptor blockade in whole blood. Agglutinization of small polymeric beads coated with a glycoprotein IIb/IIIa ligand such as fibrinogen results when the beads are contacted with whole blood containing platelets with glycoprotein IIb/IIIa receptors that are not blocked. Failure to agglutinate indicates that blockade of the GPIIb/IIIa receptors has been achieved. In a preferred embodiment, the addition of a thrombin receptor activator results in an assay that is rapid and convenient enough to be performed at the bedside and that results in agglutination of the small polymeric beads within a convenient, known period of time if the glycoprotein IIb/IIIa receptors are not blocked.

Abstract: Platelet-specific, chimeric immunoglobulin and immunoglobulin fragments are described. The chimeric molecules are made up of a nonhuman antigen binding region and a human constant region. Preferred immunoglobulins are specific for glycoprotein IIb/IIIa receptor in its complexed form; they block ligand binding to the receptor and prevent platelet aggregation. The immunoglobulins are useful in anti-thrombotic therapy when administered alone or in conjunction with thrombolytic agents, as well as in thrombus imaging.

Abstract: A peptide ligand analogue of peptide ligands derived from thrombin-cleaved thrombin receptor site on platelets resists inactivation by aminopeptidase M by substituting the .beta.-amino acid isoserine for the N-terminal serine of the peptide ligand.

Abstract: There is provided a novel monoclonal antibody fragment which inhibits platelet function and may be useful in the treatment of thrombotic diseases. The fragment is produced by proteolytic digestion of the 7E3 monoclonal antibody.

Abstract: The monoclonal antibody designate 7E3 blocks the interaction of fibrinogen with platelets, prevents thrombus formation, reacts with both human and dog platelets and fails to react with thrombasthenic human platelets or human platelets whose GPIIb/IIIa complex is dissociated with EDTA. A fragment of the 7E3 antibody can prevent occlusion by thrombus in the circulatory system.

Abstract: The present invention provides synthetic antiaggregatory agents for preventing inhibition of fibrinogen-platelet binding. These anti-aggregatory agents have the general formulas (1)-(5).H--[--(AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.j --].sub.n --Cx (1)[Ri--C(O)--R--G--D--(AA.sub.j).sub.j --].sub.n --CX (2)Cy--[--AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.i --].sub.n --Z (3)H--[--(AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.j --].sub.n --CZ--[--(AA.sub.k).sub.k --R--G--D--(AA.sub.l).sub.l --].sub.m --Z (4)[R.sub.1 --C(O)--R--G--D--(AA.sub.i).sub.i --].sub.n --CZ[--(AA.sub.j).sub.j ]--R--G--D--(AA.sub.k).sub.k --].sub.m --Z (5)in which: R=Arg; G=Gly; D=Asp; AA.sub.i, AA.sub.j, AA.sub.k and AA.sub.l = alpha-, beta- and omega-amino acid residues; (AA.sub.i).sub.i (AA.sub.j).sub.j =peptide chains having the same or different amino acid residues; (AA.sub.k).sub.k =peptide chains having the same or different amino acid residues; (AA.sub.l).sub.

Abstract: There is provided a novel monoclonal antibody of the class IgG.sub.1 which reacts readily with both normal human and dog blood platelets while failing to react with thrombasthenic human platelets. This antibody has the property of completely blocking interaction of fibrinogen with platelets induced by ADP.

Abstract: The present invention provides new compounds and methods for promoting platelet aggregation, and controlling bleeding. The present invention is based on the surprising discovery that erythrocytes conjugated to certain peptides and polypeptides containing an R-G-D (Arg-Gly-Asp) sequence (collectively termed herein "RGD peptides") according to the invention, selectively bind to activated platelets but not to unactivated platelets. In recognition of the dual nature of the derivatized erythrocytes, they are termed herein "thrombo-erythrocytes". The thrombo-erythrocytes have no significant change in their rheological properties. In a preferred aspect, the thrombo-erythrocytes have the majority of RGD peptide cross-linked specifically to glycophorin A and glycophorin B on the surface of the erythrocyte.

Abstract: The present invention relates to a novel treatment for myocardial infarction which comprises administering a hapten-binding molecule capable of preventing reformation of fibrin-platelet clots and a thrombolytic agent capable of either dissolving fibrin-platelet clots or inhibiting their formation. The therapy of the invention is capable of increasing clot lysis while minimizing fibrinogen breakdown and preventing the reocclusion of the affected coronary artery. The therapy of the present invention is capable of achieving this goal even in the absence of heparin and when the concentration of thrombolytic agent is lower than that required by other potential therapies.

Abstract: There is provided a radiolabeled monoclonal antibody of the class IgG.sub.1 which reacts readily with both normal human and dog blood platelets while failing to react with thrombasthenic human platelets. This antibody has the property of completely blocking interaction of fibrinogen with platelets induced by ADP, and the ability to detect fresh thrombi in vivo.