Hamilton Civic Hospitals Research Development Inc.

Mcmaster University

Jack Hirsh

Jeffrey I Weitz

Edward Young

Richard Carl Austin

Salim Yusuf

John Eikelboom

Kevin Teoh

Marilyn Johnston

James E Knobloch

Jeffrey Weitz

A novel method for detecting the concentration of a metabolite in a fluid sample is provided. Devices for the detection of the analyte are also provided. In particular, a device for determining the concentration of 11-dehydro thromboxane in a urine sample and comparing it to a set of standardized quartile concentrations is provided. A concentration of urinary 11-dehydro thromboxane that falls within the fourth quartile is indicative of a greatly increased risk of a recurrent cardiovascular event.

Device for measuring an analyte

A method for assessing aspirin resistance and relative risk of a cardiovascular event in a patient taking aspirin is provided. The concentration of 11-dehydro-thromboxane B2 in a urine sample is measured and compared to a set of standardized quartile concentrations. A concentration of urinary 11-dehydro-thromboxane B2 that falls within the second, third, or fourth quartile is indicative of aspirin resistance and an elevated risk of a recurrent cardiovascular event.

Method for predicting cardiovascular events

A method for diagnosing hyperhomocysteinemia by molecular genetic means is disclosed.

Methods and compositions for diagnosis of hyperhomocysteinemia

The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) inactivating fluid-phase thrombin and thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). The compositions and methods of the present invention are particularly usefull for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Modified low molecular weight heparin that inhibits clot associated

The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) selectively inactivating thrombin which is bound either to fibrin in a clot or to some other surface, but which has only minimal inhibitory activity against free thrombin, i.e., fluid-phase thrombin; (2) inhibiting the assembly of the intrinsic tenase complex, thereby inhibiting the activation of Factor X by Factor IXa; and (3) inhibiting the activation of Factor IX by Factor XIa. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Compositions and methods for inhibiting thrombogenesis

The present invention generally relates to a processes for preparing low affinity, low molecular weight heparins (LA-LWM-heparins) which are endowed with pharmacological and therapeutic properties that are surprisingly advantageous. In one embodiment, the process comprises: (1) nitrous acid depolymerization of unfractionated heparin to yield low molecular weight heparin (LMWH); (2) oxidation of the resulting LMWH to open the ring structures the nonsulfated uronic acid moieties using, for example, sodium periodate; and (3) reduction of the oxidized LMWH to reduce the aldehydes (to alcohols) formed during the depolymerization and oxidation steps using, for example, sodium borohydride. The resulting LA-LMW-heparins are capable of inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. As such, the resulting LA-LMW-heparins are useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Processes for the preparation of low-affinity, low molecular weight

The present invention provides compositions and methods for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Thrombus or clot formation and accretion are inhibited by administering thrombin-displacing substances to a patient. The thrombin-displacing substances comprise either thrombin analogs which bind to the thrombin-binding site on fibrin or fibrin analogs which bind to a fibrin-binding site on thrombin. By displacing the thrombin from clot or thrombus, the thrombin is released into circulation where it is inactivated by endogenous anti-proteinases. The fibrin analogs which bind to the fibrin-binding site on thrombin may be linked to a second binding moiety which binds to and/or inactivates the catalytic site on thrombin to further inhibit thrombosis.

Methods and compositions for inhibiting thrombogenesis

A fibrin glue includes a fibrinogen component and a thrombin component, both prepared from single donor plasma. The plasma is precipitated to produce a precipitate containing fibrinogen and a supernatant containing the thrombin. The precipitate may be resuspended in a small volume of supernatant and used as the fibrinogen component. The supernatant is further treated by clotting to convert residual fibrinogen to fibrin and filtration to remove the fibrin. The resulting serum can be used as the thrombin component.

Growing community of inventors

Hamilton, Canada

Jack Hirsh