Abstract

High shear forces can induce structural changes in the shape of the von Willebrand factor (VWF) molecule, making it more sensitive for ADAMTS-13, a specific VWF protease. This leads to proteolysis of the highest-molecular-weight multimers, which are the most effective in platelet-mediated hemostasis under conditions of high shear stress. The use of cardiopulmonary bypass (CPB) is accompanied with high shear forces and could therefore lead to diminished VWF activity. Therefore, we studied VWF activity in patients undergoing myocardial revascularization. We enrolled 60 patients undergoing coronary artery bypass graft (CABG) surgery with and without CPB (30 in each group). ADAMTS-13 activity, VWF antigen (VWF:Ag) and propeptide levels were measured directly before and after the procedure. VWF activity was determined using both the ristocetin cofactor activity (VWF:Rcof) and collagen binding (VWF:CB) assays. VWF:Rcof and VWF:CB, both corrected for VWF:Ag, were significantly increased after the procedure in the off-pump group (p < 0.001 and p = 0.05, respectively), but not in the CPB group. Postoperative VWF:Ag and VWF-propeptide levels significantly increased in both groups. ADAMTS-13 activity increased after both types of surgery after correction for hemodilution. Postoperative VWF:Rcof levels correlated with postoperative D-dimer levels (p = 0.025) and were associated with early cognitive decline in the off-pump group (p = 0.025). Our data indicate that VWF activity is increased after off-pump CABG, but not after CABG with CPB. Since release of VWF is comparable in both groups, shear stress-induced proteolysis due to the use of CPB may be responsible for the decreased VWF activity.

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