Provided is a method for purifying α-thrombin and for quantifying α-thrombin and its degradation polypeptides in a liquid proteinatious solution. The method employs a one-step anion exchange chromatography method. The method allows purification and/or quantification of a homogenous post-translationally modified α-thrombin. The method can also be used for purification and/or quantification of β-thrombin.

The present invention relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has increased F.IX clotting activity compared to wildtype. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

The present invention relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has increased F.IX clotting activity compared to wildtype. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

The present invention provides methods for identification of subjects with a rise in plasma coagulability post-diagnosis of thrombotic event (and consequent increased risk for recurrent thromboembolism) as well as for identification of subjects without thrombotic event who exhibit a rise in plasma coagulability for which prophylactic anticoagulation may be warranted for TE prevention, and other methods for identification of perioperative subjects who are at heightened risk for perioperative bleeding and/or for requiring blood transfusion, using the CloFAL assay, to aid in clinical decision making regarding anticoagulant and/or adjunctive clinical management designed to mitigate this heightened thromboembolic risk.

The present invention provides methods for identification of subjects with a rise in plasma coagulability post-diagnosis of thrombotic event (and consequent increased risk for recurrent thromboembolism) as well as for identification of subjects without thrombotic event who exhibit a rise in plasma coagulability for which prophylactic anticoagulation may be warranted for TE prevention, and other methods for identification of perioperative subjects who are at heightened risk for perioperative bleeding and/or for requiring blood transfusion, using the CloFAL assay, to aid in clinical decision making regarding anticoagulant and/or adjunctive clinical management designed to mitigate this heightened thromboembolic risk.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU/mg of defibrotide, preferably from 27 to 32 IU/mg and, more preferably, from 28 to 32 IU/mg.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU/mg of defibrotide, preferably from 27 to 32 IU/mg and, more preferably, from 28 to 32 IU/mg.

Methods and assays for determining the activation level of the plasma kallikrein (pKal) system and the uses thereof for assessing the activity of pKal modulators on the pKal system.

Methods and assays for determining the activation level of the plasma kallikrein (pKal) system and the uses thereof for assessing the activity of pKal modulators on the pKal system.

Disclosed are devices for detection of bleeding during surgical procedures and uses thereof. Also disclosed are methods of localizing a bleeding site during surgical procedures, and methods for evaluating an intensity of bleeding during the surgical procedures. The detection of bleeding is based, inter alia, on the presence of thrombin activity in a bleeding site.