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Factors for life: advances in the treatment of congenital and coagulopathic bleeding disorders1
Thrombosis Research 128 Suppl. 1 (2011) S1
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t h r o m r e s
Factors for life: advances in the treatment of congenital and coagulopathic bleeding disorders* Steven Pipea and Barbara Ziegerb Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany
a b
Bleeding disorders due to coagulopathy can be classified as congenital (e.g. hemophilia, von Willebrand disease [VWD]) or acquired (e.g. trauma- or surgery-related coagulopathic bleeding). Both types pose unique clinical challenges. Congenital bleeding disorders may necessitate long-term prophylaxis to prevent bleeding complications. Management of coagulopathic bleeding following trauma or surgery is complicated by multiple factors related to the underlying condition and treatment. CSL Behring has been providing plasma-derived and recombinant coagulation factors for patients with bleeding disorders for decades, and is committed to improving the lives of patients with both congenital and acquired bleeding disorders. On 25 July 2011, CSL Behring sponsored a symposium, entitled ‘Factors for Life: Advances in the Treatment of Congenital and Coagulopathic Bleeding Disorders’, which took place at the XXIII Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Kyoto, Japan. The wide-ranging topics covered some of the key issues involved in the treatment of patients with coagulopathic bleeding disorders, with an emphasis on new treatment approaches in development. The articles in this supplement summarize the main points made by each presenter during the symposium. Congenital bleeding disorders For patients with congenital bleeding disorders, the availability of plasmaderived and recombinant coagulation factor products has brought new options for the prevention and treatment of bleeding episodes. In the first article in this supplement, Professor Reinhard Schneppenheim reviews the physiological role of von Willebrand factor (VWF) and some of the many ways in which defects in this factor can lead to coagulopathy. Emphasis is placed on the role of VWF multimerization and how specific defects in VWF can lead to specific phenotypes, which can have important implications for treatment. Proper diagnosis and classification of VWD is therefore essential to providing optimal care to patients with VWD.
*Proceedings from the CSL Behring-sponsored symposium, held at the XXIII Congress of the International Society on Thrombosis and Haemostasis, Kyoto, Japan, 25 July 2011. Corresponding authors. Tel.: +1 734 647 2893; fax: +1 734 614-0464. E-mail address: [email protected] (S. Pipe). Tel.: +49 761 270 4300; fax: +49 761 4582. E-mail address: [email protected] (B. Zieger). 0049-3848 /$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
In the second article, Dr Stefan Schulte of CSL Behring shares some of the latest findings from the research and development teams at CSL Behring. Their research has focused on some important unmet needs related to the administration of coagulation factors in patients with hemophilia. Innovative recombinant coagulation factors have been designed with the goal of improving the pharmacokinetic and biological properties of these products. Two novel recombinant proteins were designed using albumin fusion technology to extend the half-life of recombinant factors VIIa and IX. Extending the half-life of these factors may allow for less frequent dosing, which could have a positive impact on compliance and quality of life for patients with hemophilia. In addition, a novel recombinant single-chain version of factor VIII has been developed that may improve the stability of the molecule during manufacturing as well as enhance its affinity for VWF. Acquired bleeding disorders The second half of the symposium focused on acquired bleeding disorders in trauma patients and those undergoing cardiac surgery. In the third article in this supplement, Dr Benny Sørensen reviews the essential role of fibrinogen in hemostasis, issues related to the measurement of plasma fibrinogen, and the potential role of fibrinogen concentrate as a hemostatic intervention in patients with trauma- or surgery-related bleeding. Continuing on this theme, in the final article in the supplement, Professor Niels Rahe-Meyer presents clinical trial data on the use of fibrinogen concentrate in patients undergoing aortic aneurysm graft surgery. Perioperative coagulopathic bleeding is a common complication of this type of surgery, and preliminary data suggest that fibrinogen concentrate may reduce the need for transfusion of allogeneic blood products, such as fresh frozen plasma and platelets, in this setting. We believe that the articles in this supplement will provide informative reading for those interested in recent advances in the use of coagulation factors in the management of congenital and acquired bleeding disorders.
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t h r o m r e s
Factors for life: advances in the treatment of congenital and coagulopathic bleeding disorders* Steven Pipea and Barbara Ziegerb Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany
a b
Bleeding disorders due to coagulopathy can be classified as congenital (e.g. hemophilia, von Willebrand disease [VWD]) or acquired (e.g. trauma- or surgery-related coagulopathic bleeding). Both types pose unique clinical challenges. Congenital bleeding disorders may necessitate long-term prophylaxis to prevent bleeding complications. Management of coagulopathic bleeding following trauma or surgery is complicated by multiple factors related to the underlying condition and treatment. CSL Behring has been providing plasma-derived and recombinant coagulation factors for patients with bleeding disorders for decades, and is committed to improving the lives of patients with both congenital and acquired bleeding disorders. On 25 July 2011, CSL Behring sponsored a symposium, entitled ‘Factors for Life: Advances in the Treatment of Congenital and Coagulopathic Bleeding Disorders’, which took place at the XXIII Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Kyoto, Japan. The wide-ranging topics covered some of the key issues involved in the treatment of patients with coagulopathic bleeding disorders, with an emphasis on new treatment approaches in development. The articles in this supplement summarize the main points made by each presenter during the symposium. Congenital bleeding disorders For patients with congenital bleeding disorders, the availability of plasmaderived and recombinant coagulation factor products has brought new options for the prevention and treatment of bleeding episodes. In the first article in this supplement, Professor Reinhard Schneppenheim reviews the physiological role of von Willebrand factor (VWF) and some of the many ways in which defects in this factor can lead to coagulopathy. Emphasis is placed on the role of VWF multimerization and how specific defects in VWF can lead to specific phenotypes, which can have important implications for treatment. Proper diagnosis and classification of VWD is therefore essential to providing optimal care to patients with VWD.
*Proceedings from the CSL Behring-sponsored symposium, held at the XXIII Congress of the International Society on Thrombosis and Haemostasis, Kyoto, Japan, 25 July 2011. Corresponding authors. Tel.: +1 734 647 2893; fax: +1 734 614-0464. E-mail address: [email protected] (S. Pipe). Tel.: +49 761 270 4300; fax: +49 761 4582. E-mail address: [email protected] (B. Zieger). 0049-3848 /$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
In the second article, Dr Stefan Schulte of CSL Behring shares some of the latest findings from the research and development teams at CSL Behring. Their research has focused on some important unmet needs related to the administration of coagulation factors in patients with hemophilia. Innovative recombinant coagulation factors have been designed with the goal of improving the pharmacokinetic and biological properties of these products. Two novel recombinant proteins were designed using albumin fusion technology to extend the half-life of recombinant factors VIIa and IX. Extending the half-life of these factors may allow for less frequent dosing, which could have a positive impact on compliance and quality of life for patients with hemophilia. In addition, a novel recombinant single-chain version of factor VIII has been developed that may improve the stability of the molecule during manufacturing as well as enhance its affinity for VWF. Acquired bleeding disorders The second half of the symposium focused on acquired bleeding disorders in trauma patients and those undergoing cardiac surgery. In the third article in this supplement, Dr Benny Sørensen reviews the essential role of fibrinogen in hemostasis, issues related to the measurement of plasma fibrinogen, and the potential role of fibrinogen concentrate as a hemostatic intervention in patients with trauma- or surgery-related bleeding. Continuing on this theme, in the final article in the supplement, Professor Niels Rahe-Meyer presents clinical trial data on the use of fibrinogen concentrate in patients undergoing aortic aneurysm graft surgery. Perioperative coagulopathic bleeding is a common complication of this type of surgery, and preliminary data suggest that fibrinogen concentrate may reduce the need for transfusion of allogeneic blood products, such as fresh frozen plasma and platelets, in this setting. We believe that the articles in this supplement will provide informative reading for those interested in recent advances in the use of coagulation factors in the management of congenital and acquired bleeding disorders.