Acquired intracoronary ADAMTS 13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI

von Willebrand factor (VWF) mediates platelet adhesion and agglutinationat sites of vascular injury.VWFis a largemultimericglycoprotein, which circulates in a coiled, non-adhesive conformation.When exposed to high shear stress, VWF unfolds and elongates to highly adhesive multimer strands that adhere on exposed collagen fibers, and by interacting with platelet glycoprotein Ib-a, recruit platelets to the injury site. Recent in vivo work showed that transition from laminar to turbulent flow, as observed at sites of stenotic vessels, is the most important trigger for adhesive conformational change of VWF. Additionally, the ability of VWF to tether platelets is directly proportional to its multimeric size. The latter is regulated by ADAMTS13 (a disintegrin andmetalloproteasewith thrombospondin type-1 repeats, member 13), a metalloprotease that cleaves VWFmultimers within the unfolded A2 domain, thereby reducing VWF multimer size, and by this, decreasing VWF adhesiveness. We postulated that transition from laminar to turbulent flow at sites of critical coronary stenosismay cause a local imbalance betweenVWF and ADAMTS13, which would be responsible for the presence of highly adhesive VWF multimers mediating platelet adhesion and agglutination, and ultimately responsible for acute occlusion. The aim of this investigation was to evaluate systemic and intracoronary thrombin generation, VWF, and ADAMTS13 activity in patients with acute coronary syndromes (ACS) with angiographic evidence of acute thrombotic coronary occlusion. We investigated 27 patients (24 men; median age, 65 years; interquartile range [IQR], 54-74; range, 41-84) undergoing emergency cardiac catheterization for hemodynamically stable ACS presenting with ST-elevation myocardial infarction (STEMI) who gave written informed consent. The culprit lesion was determined angiographically in two orthogonal projections and was defined by the combination of: (1) abrupt (typical) vessel occlusion; and (2) complete absence of (or severely impaired) peripheral coronary flow. Infarct localization was anterior in 9 patients, infero-posterior in 16, and lateral in 2. Maximal creatine kinase value was median 1440 U/L (IQR, 922-2262; range, 750-5800) and the extent of the underlying coronary artery disease assessed by the Syntax score was 17 6 7. All patients underwent percutaneous coronary intervention/stenting with a median time from chest pain to onset-balloon of 105 minutes (IQR, 62-150; range, 20-1140). Blood samples were obtained at 3 different sites before stenting: from the femoral vein and at the ostia of the right or left coronary artery through a coronary guiding 6 French catheter, and 1-3 cm distal to the site of occlusion with a conventional 6 French compatible thrombus aspiration catheter advanced through the lesion. In a preliminary phase, we verified that blood sampling by coronary catheter did not alter results for thrombin-generation markers, VWF, and ADAMTS13 compared with peripheral venipuncture. Additionally, care was taken to perform extra slow aspiration to avoid turbulences inside the catheter. Samples were collected into citrate test tubes, snap-frozen immediately after centrifugation, and kept at 280°C until batch analysis. Markers of thrombin generation and VWF antigen (VWF: Ag) were assessed by enzyme-linked immunosorbent assay and VWF activity (VWF:RCo) by a turbidimetric method as published. ADAMTS13 activity was measured by the fluorescence resonance energy transfer-VWF73 assay as previously described. Our results show that parameters of thrombin generation, ie, prothrombin fragments 112 (F112), thrombin-antithrombin complexes