Therapy for von Willebrand disease (VWD) aims to restore the hemostatic function conferred by von Willebrand factor (VWF), which facilitates platelet adhesion and aggregation, and serves to increase potentially low coagulation factor VIII (FVIII) in plasma. In patients unresponsive to desmopressin (DDAVP), the preferred treatment is with plasma-derived VWF-containing FVIII concentrates. Only a few of the available VWF/FVIII concentrates have been licensed for use in VWD based on prospective studies. The efficacy of VWF/FVIII concentrates depends on the content and quality of VWF and FVIII. Several studies have demonstrated the variability of the VWF contents, as well as the differences in the VWF multimer patterns (including the high molecular weight VWF multimers that are most effective in restoring hemostasis), among these concentrates. Treating physicians should be aware of these disparities and the potential clinical implications for patients with different VWD subtypes. Dosing has traditionally been calculated based on the FVIII content of the products, although dosing based on VWF functional activity [e.g., VWF ristocetin cofactor activity (VWF:RCo)] addresses the primary protein deficiency in VWD patients. Several clinical studies have demonstrated the efficacy of concentrates dosed according to VWF:RCo. Dosing is generally consistent across VWD subtypes, although patients with severe phenotypes or undergoing major procedures may require more infusions or longer treatment duration. Other considerations for the use of VWF-containing concentrates include laboratory monitoring of efficacy and safety issues such as thrombosis risk and thromboprophylaxis.

4657 Background Several studies have shown that between 15% to 25% of patients with severe aortic stenosis present bleeding episodes that may be attributed to an acquired von Willebrand syndrome (AVWS). Until now, to our knowledge, no association of AVWS with mitral valve disfunction has been reported. Design and Methods Four patients with mitral valve leak presented acquired abnormalities of von Willebrand factor (VWF) and a bleeding history. Two of them presented severe bleedings requiring blood transfusions. All of them were within an adequate range of oral anticoagulation. Results Prior to surgery, these patients presented an APTT prolonged and in two of them the closure time determined by the platelet function analyzer (PFA-100®) (with COL/ADP and COL/Epi) was prolonged also. Factor VIII procoagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) and VWF collagen binding (VWF:CB) were considerably elevated and the VWF multimers in plasma, showed a lower relative proportion of the high molecular weight VWF multimers (HMWM), to some extent similar to type 2A congenital von Willebrand disease (VWD). In two of them, the VWF:RCo/VWF:Ag or VWF: CB/VWF:Ag ratios were less than normal range (>0.7) while in the other two were normal. After surgery, FVIII:C, and VWF properties were extremely increased and the ratios VWF:RCo/VWF:Ag and VWF: CB/VWF:Ag > 0.7. After surgery, FVIII:C, VWF:Ag, VWF:RCo and VWF:CB increased considerably. The ratios were > 0.7. The PFA-100® (COL/ADP and COL/Epi) was corrected in the two patients who had it prolonged. The multimeric VWF profile were also corrected in all of them. Conclusions The present study describes acquired VWF qualitative alterations for the first time in mitral valve leak. When such alterations are important they may be associated or to contribute to a bleeding diathesis. This problem was reported previously in aortic valve stenosis in relationship with a suspected very high shear stress. This situation may be not usually present in mitral valve stenosis, but it seems that it must occur in the presence of mitral valve leak. Consequently, the AVWS should be taken into account in patients with mitral valve leak that present a bleeding diathesis, not explained by an excess of oral anticoagulation. ACKNOWLEDGEMENTS This work was supported by the Fondo de Investigación Sanitaria, F.I.S. Carlos III, Ministerio de Sanidad, Spain (FIS PI# 07/0229), and Consellería de Innovación e Industria, Xunta de Galicia (INCITE08ENA916109ES). Disclosures: No relevant conflicts of interest to declare.