These findings were probably related to increased plasma VWF levels, appearance of ultra-large multimers in the circulation and secretion of VWF abluminally from endothelial cells. However, these mechanisms do not explain the shortening of bleeding time observed in patients with BSS who lack glycoprotein Ibα, the receptor of VWF, and raise

the possibility that desmopressin exerts an additional VWF-independent effect on haemostasis. In 1996, Tengborn and Petruson reported a 2-year-old boy with GT in whom find more high dose rFVIIa administration resulted in controlling severe epistaxis [15]. Since then, additional cases, mostly with GT, have been treated for bleeding episodes by rFVIIa with partial Target Selective Inhibitor Library success [16,17]. The mechanism by which rFVIIa arrests bleeding in a fraction of patients with GT has not been rigorously elucidated, but has been attributed to: (i) Increased thrombin generation related to direct activation of factor X by rFVIIa bound to platelet surfaces by a tissue factor-independent mechanism [18]. (ii) Enhanced adhesion of platelets to endothelial extracellular matrix

and collagen under flow conditions by the generated thrombin [19]. (iii) Restoration of platelet aggregation in the presence of factor X, factor II and fibrinogen by polymerizing fibrin formed by the tissue factor-independent thrombin generation [20]. The use

of r-FVIIa in patients with inherited platelet dysfunction selleck chemicals llc has not been examined by randomized controlled studies. The largest experience has been obtained in patients with GT by Poon et al. [16,17,21]. These investigators organized an international survey the objective of which was to examine the efficacy of rFVIIa infusion in GT patients. Fifty-nine patients were enrolled in 49 medical centres and were treated with rFVIIa during 108 bleeding episodes and during 34 surgical procedures. For the bleeding episodes, the success rate was 69/108 (75%), and for the surgical procedures, 29/34 (94%). The regimen used in most patients consisted of at least 80 μG Kg−1 rFVIIa administered intravenously every 2.5 h. The success rate in patients with gastrointestinal bleeding was low 8/17 (47%) and for dental extraction, it was high 9/9 (100%). In another study of seven children with GT (five patients), BSS (one patient) and storage pool disease (one patient), the success rate of rFVIIa infusion alone during bleeding episodes was only 10/28 (36%) [22]. Response was excellent during three bleeding episodes in the patient with BSS and during two bleeding episodes in the patient with storage pool disease. These results are less promising than the results of the international survey and thus further studies are warranted.