Columbia University

Eric A Rose

David M Stern

Ann Marie Schmidt

David J Pinsky

Talia Spanier

Arthur Dresdale

Robert A Solomon

E Sander Connolly, Jr

Charles J Prestigiacomo

This invention provides a method for inhibiting thrombosis in a patient whose blood is subjected to extracorporeal blood circulation which comprises contacting the extracorporeal circulating blood with a Factor IXa compound in an amount effective to inhibit thrombosis in the blood of a patient and under conditions such that the Factor IXa compound circulates in the patient. The Factor IXa compound may include an active site-blocked Factor IXa compound or Glu-Gly-Arg chloromethyl ketone-inactivated human factor IXa compound. This invention also provides that the effective amount may be from about 0.1 &mgr;g/ml plasma to about 250 &mgr;g/ml plasma or from about 0.5 &mgr;g/ml plasma to about 25 &mgr;g/ml plasma. The patient may be subjected to extracorporeal blood circulation during transplant surgery or cardiopulmonary bypass surgery. This invention further provides for a method for inhibiting thrombosis in a patient whose blood is subjected to extracorporeal blood circulation, which comprises contacting the extracorporeal circulating blood with an agent capable of inhibiting a step of the intrinsic pathway of coagulation in an amount effective to inhibit thrombosis in the blood of a patient and under conditions such that the Factor IXa compound circulates in the patient. The agent may be an active site-blocked Factor XII compound or an active site-blocked Factor XI compound.

Method for inhibiting thrombosis in a patient whose blood is subjected to extracorporeal circulation

The present invention provides for a method for treating an ischemic disorder in a subject which comprises administering to the subject a pharmaceutically acceptable Factor IXa compound in a sufficient amount over a sufficient time period so as to treat the ischemic disorder in the subject. The invention further provides a method for treating an ischemic disorder in a subject which comprises administering to the subject a pharmaceutically acceptable form of inactivated Factor IXa in a sufficient amount over a sufficient period of time to inhibit coagulation so as to treat the ischemic disorder in the subject.

Methods for treating an ischemic disorder and improving stroke outcome

The present invention provides for a method of treating an ischemic disorder in a subject which comprises administering to the subject a pharmaceutically acceptable form of inactivated Factor IX in a sufficient amount over a sufficient period of time to inhibit coagulation so as to treat the ischemic disorder in the subject.

This invention provides an assay to monitor antithrombic activity of a Factor IXa compound infused into circulation of a patient which includes: (a) obtaining Factor IXa-deficient plasma; (b) mixing the plasma from step (a) with diatomaceous and with plasma from the patient; (c) incubating the mixture with a source of lipid and calcium chloride under conditions suitable for clot formation; and (d) measuring time necessary for clot formation in the incubate, thereby monitoring the antithrombic activity of the Factor IXa compound infused into the circulation of the patient.

Method for inhibiting thrombosis in a patient whose blood is subjected

This invention concerns a method of preparing a cryoprecipitated suspension containing fibrinogen and Factor XIII useful as a precursor in the preparation of a fibrin glue which involves (a) freezing fresh frozen plasma from a single donor such as a human or other animal, e.g., a cow, sheep or pig, which has been screened for blood transmitted diseases, e.g., one or more of syphilis, hepatitis or acquired immune deficiency syndrome at about -80.degree. C. for at least 6 hours, preferably for at least about 12 hours; (b) raising the temperature, so as to form a supernatant and a cryoprecipitated suspension containing fibrinogen and Factor XIII; and (c) recovering the cryopricipitated suspension.

Method of preparing a cryoprecipitated suspension and use thereof

This invention concerns a method of preparing a cryoprecipitated suspension containing fibrinogen and Factor XIII useful as a precursor in the preparation of a fibrin glue which involves (a) freezing fresh frozen plasma from a single donor such as a human or other animal, e.g. a cow, sheep or pig, which has been screened for blood transmitted diseases, e.g. one or more of syphilis, hepatitis or acquired immune deficiency syndrome at about =80.degree. C. for at least about 6 hours, preferably for at least about 12 hours; (b) raising the temperature of the frozen plasma, e.g. to between about 0.degree. C. and room temperature, so as to form a supernatant and a cryoprecipitated suspension containing fibrinogen and Factor XIII; and (c) recovering the cryoprecipitated suspension. The invention also concerns a method of preparing a fibrin glue useful in surgical procedures which comprises: (a) preparing a cryoprecipitated suspension as described above; (b) applying a defined volume of the suspension to a desired site; and (c) applying a composition containing a sufficient amount of thrombin, e.g. human, bovine, ovine or porcine thrombin, to the site so as to cause the fibrinogen in the suspension to be converted to the fibrin glue which then solidifies in the form of a gel. The thrombin-containing composition may also contain a suitable amount of an anti-fibrinolytic substance, e.g. aprotinin and a suitable amount of CaCl.sub.2. The invention also concerns the cryoprecipitated suspension, the fibrin glue formed therefrom, fibrin glue kits and a method for sealing surgical wounds.

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Tenafly, NJ, United States of America

Eric A Rose