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A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.

 

The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.

An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.

The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.

Dr. Repesse reported having no disclosures.

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A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.

 

The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.

An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.

The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.

Dr. Repesse reported having no disclosures.

A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.

 

The in vitro production and characterization of these solulin variants – F376A-, M388A-, and F376A/M388A-solulin – showed that while they lost their abilities to activate protein C (an inhibitor of thrombin generation), they were still capable of activating thrombin activatable fibrinolysis inhibitor (TAFI), Yohann Repesse, PhD reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

Additionally, the double mutant F376A/M388A-solulin, which was tested ex vivo using blood samples from hemophilic A patients, was found on thromboelastography to increase clot firmness and stability. As opposed to wild type solulin, the effects were maintained even at high concentrations of F376A/M388A-solulin, said Dr. Repesse of the National Institute of Health and Medical Research, Caen, France.

An important aggravating factor when it comes to treating hemophilia involves premature fibrinolysis, which means that antifibrinolytics are of interest, he explained. Thrombomodulin is a key player in the coagulation cascade, because it activates protein C, and also in the fibrinolytic cascade, as it activates TAFI. Solulin, a soluble form of thrombomodulin, has both capabilities.

The findings with respect to the new generation of solulin variants tested in this study open new opportunities for the development of specific medications for hemophilia patients, he concluded.

Dr. Repesse reported having no disclosures.

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Key clinical point: A new generation of solulin variants is showing promise for the treatment of severe hemophilia A.

Major finding: F376A-, M388A-, and F376A/M388A-solulin lost their abilities to activate protein C but were still capable of activating TAFI.

Data source: An in vitro and ex vivo evaluation of solulin variants.

Disclosures: Dr. Repesse reported having no disclosures.