A new recombinant factor VIII: from genetics to clinical use

Christoph Kannicht,1 Guido Kohla,1 Maya Tiemeyer,2 Olaf Walter,3 Helena Sandberg4 1Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany; 2Octapharma Biopharmaceuticals GmbH, Heidelberg, Germany; 3Octapharma AG, Lachen, Switzerland; 4CoaBio AB, Bromma, SwedenThe December 2014 issue of Drug Design, Development and Therapy included a review article by Santagostino entitled “A new recombinant factor VIII: from genetics to clinical use”.1 The article provided a timely review of recent advances and developments in the treatment of hemophilia A with recombinant factor VIII (rFVIII).1 However, when reviewing licensed rFVIII products, Santagostino1 did not include Human-cl rhFVIII (simoctocog alfa, Nuwiq®).2–4 Nuwiq® is a new-generation rFVIII protein produced in HEK 293 F cells that was approved by the European Medicines Agency in July 2014 for the prevention and treatment of bleeds in hemophilia A patients of all ages.5 Read the original article&nbsp

Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding

Patients undergoing major cardiothoracic surgery are subjected to dilution, owing to massive fluid infusion and blood component transfusion. These patients may experience bleeding perioperatively, and are frequently treated with the endothelium-activating agent desmopressin.status: publishe

Third Åland islands conference on von Willebrand disease, 26-28 September 2012: meeting report.

The first meeting of international specialists in the field of von Willebrand disease (VWD) was held in the Åland islands in 1998 where Erik von Willebrand had first observed a bleeding disorder in some members of a family from Föglö and a summary of the meeting was published in 1999. The second meeting was held in 2010 and a report of the meeting was published in 2012. Topics covered included progress in understanding of VWD over the last 50 years; multimers; classification of VWD; pharmacokinetics and laboratory assays; genetics; treating the paediatric patient; prophylaxis; geriatrics; gene therapy and treatment guidelines. This third meeting held over 3 days covered the structure and function of von Willebrand factor (VWF); type 1 VWD, the most common form of the disease; a lifespan of pharmacokinetics in VWD; detecting inhibitors in VWD patients; and special challenges in understanding and treating the female VWD patient

Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding

Background Patients undergoing major cardiothoracic surgery are subjected to dilution, owing to massive fluid infusion and blood component transfusion. These patients may experience bleeding perioperatively, and are frequently treated with the endothelium-activating agent desmopressin. ObjectivesTo investigate the effect of desmopressin administration on von Willebrand factor (VWF)-dependent coagulant and platelet functions under flow conditions. Patients/methodsBlood from 16 patients with postoperative bleeding was obtained before and after desmopressin treatment (0.3gkg(-1) body weight), and assessed for coagulant properties and platelet function. Furthermore, VWF antigen levels and multimer composition were determined in both samples. ResultsDesmopressin treatment did not change thrombin generation in plasma or whole blood thromboelasticity. Also coagulation factor levels (other than factorVIII) and coagulation times were unchanged, suggesting that desmopressin treatment did not have a major effect on the coagulant activity. On the other hand, desmopressin treatment raised the already high plasma levels of VWF from a median of 116IUmL(-1) (interquartile range [IQR]102-154IUmL(-1)) to a median of 160IUmL(-1) (IQR126-187IUmL(-1)) (P=0.007), owing to accumulation of the high molecular weight VWF multimers. Furthermore, desmopressin treatment caused an increase in collagen-dependent thrombus formation and platelet phosphatidylserine exposure. Markers of thrombus formation correlated with the plasma levels of VWF. Invitro control experiments confirmed a major contribution of VWF to thrombus formation and procoagulant activity under conditions of blood dilution. ConclusionsDesmopressin treatment of patients with bleeding complications after cardiothoracic surgery induces the release of high molecular weight VWF multimers, which enhance platelet activation and thrombus formation under flow conditions