Acquired Von Willebrand Syndrome In Mitral Valve Leak

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.

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.

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.

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.

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).

No relevant conflicts of interest to declare.